1 00:00:05,000 --> 00:00:08,800 >>WELCOME EVERYBODY TO THE 2 00:00:08,800 --> 00:00:09,560 WALS LECTURE. 3 00:00:09,560 --> 00:00:12,760 IT'S MY VERY GREAT PLEASURE TO 4 00:00:12,760 --> 00:00:20,840 INTRODUCE TO YOU DR. 5 00:00:20,840 --> 00:00:27,760 LUNA DIATCHENKO, AND SHE 6 00:00:27,760 --> 00:00:30,680 HAS APPOINTMENTS ON THE FACULTY 7 00:00:30,680 --> 00:00:32,560 OF MEDICINE AND WITHIN THE 8 00:00:32,560 --> 00:00:35,640 FACULTY OF DENTISTRY AT 9 00:00:35,640 --> 00:00:41,440 McGILL UNIVERSITY IN 10 00:00:41,440 --> 00:00:42,000 MONTREAL. DOCTOR 11 00:00:42,000 --> 00:00:43,160 DIATCHENKO AND I FIRST MET WHEN 12 00:00:43,160 --> 00:00:46,320 SHE BECAME A GRANTEE OF NIDCR 13 00:00:46,320 --> 00:00:47,560 DURING MY TENURE AS DIRECTOR 14 00:00:47,560 --> 00:00:49,480 THERE AND I THINK THAT MIGHT 15 00:00:49,480 --> 00:00:53,800 HAVE BEEN HER FIRST NIH GRANTS 16 00:00:53,800 --> 00:00:56,040 BUT I'LL LET HER CORRECT ME IF I 17 00:00:56,040 --> 00:00:59,200 MISSPOKE AND I WILL TELL YOU AT 18 00:00:59,200 --> 00:01:02,440 THAT TIME, HER GROUND BREAKING 19 00:01:02,440 --> 00:01:04,520 WORK REALLY OFFERED NOVEL 20 00:01:04,520 --> 00:01:06,600 MECHANISTIC AND GENETIC INSIGHTS 21 00:01:06,600 --> 00:01:08,880 INTO CHRONIC PAIN AND REALLY 22 00:01:08,880 --> 00:01:11,360 REPRESENTED A MUCH WELCOME 23 00:01:11,360 --> 00:01:14,000 DEPARTURE FROM THE EXISTING 24 00:01:14,000 --> 00:01:16,040 PORTFOLIO THAT THE INSTITUTE HAD 25 00:01:16,040 --> 00:01:20,920 AT THE TIME AND I HAVE TO SAY, 26 00:01:20,920 --> 00:01:23,320 IN MANY WAYS, HER WORK CATALYZED 27 00:01:23,320 --> 00:01:26,800 A REAL SHIFT INTO THE FUTURE 28 00:01:26,800 --> 00:01:29,000 DIRECTIONS OF PAIN RESEARCH AT 29 00:01:29,000 --> 00:01:30,560 NIDCR AND BEYOND AND SO FOR THAT 30 00:01:30,560 --> 00:01:33,960 WE ARE VERY GRATEFUL TO YOU. 31 00:01:33,960 --> 00:01:36,080 NOW, I COULD SAKE A LOT OF THE 32 00:01:36,080 --> 00:01:38,520 REST OF THE TIME ALLOTTED FOR 33 00:01:38,520 --> 00:01:42,960 THIS PRESENTATION TO OUTLINE THE 34 00:01:42,960 --> 00:01:47,120 MANY HONORS THAT L UDA HAS 35 00:01:47,120 --> 00:01:49,760 GAINED BUT LET ME JUST NAME A 36 00:01:49,760 --> 00:01:50,200 FEW. 37 00:01:50,200 --> 00:01:53,560 FOR EXAMPLE N2019 SHE RECEIVED 38 00:01:53,560 --> 00:01:55,160 THE FUTURE OF PAIN SCIENCE AWARD 39 00:01:55,160 --> 00:01:57,240 FROM THE AMERICAN PAIN SOCIETY, 40 00:01:57,240 --> 00:02:08,680 SHE'S AN HONORARY PROFESSOR AT 41 00:02:08,680 --> 00:02:09,320 [INDISCERNIBLE] UNIVERSITY--AND 42 00:02:09,320 --> 00:02:10,560 FOR THOSE OF YOU NOT FAMILIAR 43 00:02:10,560 --> 00:02:15,360 WITH THE CANADIAN SYSTEM, THAT'S 44 00:02:15,360 --> 00:02:17,120 A BIG DEAL SO CONGRATULATIONS ON 45 00:02:17,120 --> 00:02:17,320 THAT. 46 00:02:17,320 --> 00:02:21,280 SO WITH THAT I, I WILL LIKE TO 47 00:02:21,280 --> 00:02:25,760 WELCOME EVERYBODY AND WELCOME 48 00:02:25,760 --> 00:02:27,600 DR. DIATCHENKO 49 00:02:27,600 --> 00:02:34,520 AND THE FLOOR IS YOURS. 50 00:02:34,520 --> 00:02:37,840 >> THANK YOU SO MUCH, I REMEMBER 51 00:02:37,840 --> 00:02:40,320 VIVIDLY OUR FIRST INTERACTION, 52 00:02:40,320 --> 00:02:44,120 TOO AND SO THAT WAS THE FIRST 53 00:02:44,120 --> 00:02:51,080 GRANT FOR GENETIC OF PAIN NIDCR 54 00:02:51,080 --> 00:02:53,200 STUDYING THE GENE WHICH WAS THE 55 00:02:53,200 --> 00:02:54,280 [INDISCERNIBLE] TRANSFER ACE, 56 00:02:54,280 --> 00:02:55,600 AND I THINK WILL BE INTERESTING 57 00:02:55,600 --> 00:02:59,040 FOR YOU TO KNOW, LARRY THAT 58 00:02:59,040 --> 00:03:04,120 TODAY IT IS THE MOST STUDIED 59 00:03:04,120 --> 00:03:04,320 GENE. 60 00:03:04,320 --> 00:03:07,840 SO WE DO ALL THIS WORK AND MANY, 61 00:03:07,840 --> 00:03:11,400 MANY PEOPLE USE OUR RESULTS AND 62 00:03:11,400 --> 00:03:14,400 IT'S A MOST SCIENTIFIC HUMAN 63 00:03:14,400 --> 00:03:14,640 IMAGING. 64 00:03:14,640 --> 00:03:17,080 SO THANK YOU VERY MUCH FOR THIS 65 00:03:17,080 --> 00:03:28,520 OPPORTUNITY TO PRESENT MY 66 00:03:28,520 --> 00:03:29,920 RESEARCH TODAY. 67 00:03:29,920 --> 00:03:34,160 I WILL START TO SHARE WITH YOU 68 00:03:34,160 --> 00:03:35,520 THE MOST EXCITING LINE I HAVE 69 00:03:35,520 --> 00:03:44,920 RIGHT NOW IN MY PROGRAM. 70 00:03:44,920 --> 00:03:49,000 OH AND I WILL START WITH THE 71 00:03:49,000 --> 00:03:51,200 OPENING REMARK THAT PAIN IS THE 72 00:03:51,200 --> 00:03:52,280 MOST PREVALENT DISEASE, YOU CAN 73 00:03:52,280 --> 00:03:54,800 SEE IT HERE, IT'S A SOCIETAL 74 00:03:54,800 --> 00:03:56,280 COST OF THE CHRONIC PAIN AND 75 00:03:56,280 --> 00:03:59,520 THOSE WHO ARE NOT IN THE PAIN 76 00:03:59,520 --> 00:04:03,760 FIELD OFTEN FIND THIS SURPRISING 77 00:04:03,760 --> 00:04:07,840 THAT THE CAUSE OF THE PAIN IS 78 00:04:07,840 --> 00:04:09,280 HIGHER THAN CANCER AND DIABETES 79 00:04:09,280 --> 00:04:11,400 COMBINED AND IF YOU CAN SEE BY 80 00:04:11,400 --> 00:04:16,120 THE GRAY BAR HERE, NIH FUNDING 81 00:04:16,120 --> 00:04:19,280 IS STILL NOT CATCHING UP WITH 82 00:04:19,280 --> 00:04:20,640 THE SOCIETAL CAUSE, ESPECIALLY 83 00:04:20,640 --> 00:04:24,480 IF YOU COMPARE WITH THEM IN THE 84 00:04:24,480 --> 00:04:27,000 FIELD IN THE SIZE OF THE FIELD, 85 00:04:27,000 --> 00:04:33,720 THE SEARCH FIELD OF THE PAIN. 86 00:04:33,720 --> 00:04:41,400 SO IT IS BEYOND OUR--ALL OF US 87 00:04:41,400 --> 00:04:43,000 FEEL THIS WAY FOR SLOW 88 00:04:43,000 --> 00:04:51,760 PROGRESSION IN THE PAIN FIELD 89 00:04:51,760 --> 00:04:55,160 THE PROGRAM I WOULD SAY IS PAIN 90 00:04:55,160 --> 00:04:57,240 IS RISING ADDICTION IN AMERICA, 91 00:04:57,240 --> 00:05:00,240 SO UNDERSTANDING OF 92 00:05:00,240 --> 00:05:00,960 PATHOPHYSIOLOGY OF THE CHRONIC 93 00:05:00,960 --> 00:05:10,640 PAIN WILL ALSO HELP US TO FIGHT 94 00:05:10,640 --> 00:05:12,920 ADDICTION. 95 00:05:12,920 --> 00:05:15,800 SO SAYING THAT PATHOPHYSIOLOGY 96 00:05:15,800 --> 00:05:19,640 OF CHRONIC PAIN IS NOT WELL IN 97 00:05:19,640 --> 00:05:21,200 THIS BOOK. 98 00:05:21,200 --> 00:05:28,600 SO WE DO KNOW THAT AFTER INJURY, 99 00:05:28,600 --> 00:05:31,800 WE HAVE PERIPHERAL ACTIVITY AND 100 00:05:31,800 --> 00:05:34,160 PERIPHERAL SENSITIZATION LEADING 101 00:05:34,160 --> 00:05:34,920 TO CENTRAL SENSITIZATION WHICH 102 00:05:34,920 --> 00:05:41,200 LEADS TO THE SYMPTOMS OF CHRONIC 103 00:05:41,200 --> 00:05:41,480 PAIN. 104 00:05:41,480 --> 00:05:42,040 BUT [INDISCERNIBLE] 105 00:05:42,040 --> 00:05:43,520 PATHOPHYSIOLOGY OF CHRONIC PAIN 106 00:05:43,520 --> 00:05:45,400 IS LARGELY UNKNOWN. 107 00:05:45,400 --> 00:05:47,000 SO THOSE RIGHT NOW IN THOSE FROM 108 00:05:47,000 --> 00:05:48,320 THE PAIN FIELD, THEY WILL TELL 109 00:05:48,320 --> 00:05:55,040 ME, THEY KNOW A LOT ABOUT 110 00:05:55,040 --> 00:05:56,200 MOLECULAR PATHOPHYSIOLOGY OF 111 00:05:56,200 --> 00:05:58,440 PAIN ABOUT BUT WE WOULD ARGUE WE 112 00:05:58,440 --> 00:06:05,440 KNOW A LOT ABOUT HYPER 113 00:06:05,440 --> 00:06:05,880 SENSITIVITY. 114 00:06:05,880 --> 00:06:11,000 BUT NOT WITH HUMAN CHRONIC PAIN. 115 00:06:11,000 --> 00:06:13,400 AND WHAT I DO IN MY LAB AND I 116 00:06:13,400 --> 00:06:20,320 DID FROM THE BEGINNING IS I 117 00:06:20,320 --> 00:06:22,600 STUDY A HUMAN PATHOPHYSIOLOGY 118 00:06:22,600 --> 00:06:24,360 THROUGH RUMAN GENETIC STUDY AND 119 00:06:24,360 --> 00:06:26,600 I WILL TELL YOU THAT YOU KNOW 120 00:06:26,600 --> 00:06:29,760 WHY I BELIEVE IT'S VERY 121 00:06:29,760 --> 00:06:35,240 PRODUCTIVE FRUIT, THIS IS 122 00:06:35,240 --> 00:06:36,280 BECAUSE [INDISCERNIBLE] THE 123 00:06:36,280 --> 00:06:38,000 PATHOPHYSIOLOGY OF CHRONIC PAIN, 124 00:06:38,000 --> 00:06:41,120 IT'S VERY DIFFICULT TO MAKE THE 125 00:06:41,120 --> 00:06:48,200 ANIMAL MODEL OF SUCH, RIGHT? 126 00:06:48,200 --> 00:06:51,560 SO, MY GROUP WAS PRODUCTIVE AND 127 00:06:51,560 --> 00:06:52,960 SUCCESSFUL IS TO TAKE 128 00:06:52,960 --> 00:07:01,280 INFORMATION FROM HUMAN STUDIES 129 00:07:01,280 --> 00:07:09,120 AND THEN KIND OF--BIOLOGY, YOU 130 00:07:09,120 --> 00:07:11,800 KNOW WE HAVE THE DNA AND RNA 131 00:07:11,800 --> 00:07:17,160 PROTEIN WHICH THEN TRANSLATED TO 132 00:07:17,160 --> 00:07:17,400 PHENOTYPE. 133 00:07:17,400 --> 00:07:24,200 SO IN ALL THE STAGES, WE CAN 134 00:07:24,200 --> 00:07:26,200 LOOK FOR BIOMARKER AND WE ALSO 135 00:07:26,200 --> 00:07:28,920 CAN LOOK FOR THIS INFORMATION 136 00:07:28,920 --> 00:07:36,400 ABOUT WHAT'S ACTUALLY HAPPENED 137 00:07:36,400 --> 00:07:37,160 WITH THE BODY. 138 00:07:37,160 --> 00:07:40,400 YEAH AND FOR EXAMPLE, ASSOCIATED 139 00:07:40,400 --> 00:07:44,520 MOLECULES, WE CAN USE IT VERY 140 00:07:44,520 --> 00:07:45,800 PRODUCTIVELY IN THE PERSONALIZED 141 00:07:45,800 --> 00:07:48,520 MEDICINE BUT ALSO JUST FOR THE 142 00:07:48,520 --> 00:07:54,600 ROLE OF BIOLOGICAL INSIGHTS. 143 00:07:54,600 --> 00:07:55,840 NOW I WILL START WITH GENETIC 144 00:07:55,840 --> 00:07:57,680 AND I WILL GIVE YOU A FEW 145 00:07:57,680 --> 00:08:00,040 EXAMPLES, SO I WILL START WITH 146 00:08:00,040 --> 00:08:06,400 GENETIC AND WHEN WE TALK ABOUT 147 00:08:06,400 --> 00:08:07,560 VARIABILITY, GENETIC 148 00:08:07,560 --> 00:08:12,600 VARIABILITY, WE KNOW THERE IS 149 00:08:12,600 --> 00:08:13,920 FAMILIARIAL, IN THOSE IT IS 150 00:08:13,920 --> 00:08:16,760 [INDISCERNIBLE] WHICH IS COMMON 151 00:08:16,760 --> 00:08:19,040 IN POPULATION. 152 00:08:19,040 --> 00:08:20,920 IN TERMS OF MONOGENIC DISORDERS, 153 00:08:20,920 --> 00:08:23,720 THERE ARE A NUMBER OF GENE HAS 154 00:08:23,720 --> 00:08:28,520 BEEN IDENTIFIED WHICH IS 155 00:08:28,520 --> 00:08:29,960 RESPONSIBLE FOR SOME VERY SEVERE 156 00:08:29,960 --> 00:08:33,080 CHRONIC PAIN CONDITION AND THE 1 157 00:08:33,080 --> 00:08:42,040 IN WHICH PEOPLE OFTEN RECOGNIZE 158 00:08:42,040 --> 00:08:43,560 IS CONGENITAL INSENSITIVITY TO 159 00:08:43,560 --> 00:08:46,200 PAIN, WHEN PEOPLE ARE UNABLE TO 160 00:08:46,200 --> 00:08:47,520 FEEL PAIN, AND THE HIGHEST 161 00:08:47,520 --> 00:08:52,240 ATTENTION HAS BEEN DRAWN TO SO 162 00:08:52,240 --> 00:08:55,640 THE SODIUM CHANNEL OF NAV1.7 163 00:08:55,640 --> 00:08:57,200 BECAUSE WHAT HAS BEEN IDENTIFIED 164 00:08:57,200 --> 00:09:05,000 IS THE NEW MUTATION, WHICH 165 00:09:05,000 --> 00:09:06,800 PEOPLE TO HAVE THE INABILITY TO 166 00:09:06,800 --> 00:09:09,200 FEEL PAIN BUT ALSO THE MUTATION 167 00:09:09,200 --> 00:09:10,520 WHICH LEAD TO CONSTANT INCREASE 168 00:09:10,520 --> 00:09:15,920 OF THE RECEPTOR ACTIVITY IN 169 00:09:15,920 --> 00:09:17,600 WHICH TUNE [INDISCERNIBLE] PAIN. 170 00:09:17,600 --> 00:09:19,760 BUT STILL WE CAN DID SOMETHING 171 00:09:19,760 --> 00:09:20,560 ABOUT PATHOPHYSIOLOGY OF CHRONIC 172 00:09:20,560 --> 00:09:26,200 PAIN FROM THE LIST OF THE 173 00:09:26,200 --> 00:09:30,120 MANAGING DISORDERS BUT YOU KNOW 174 00:09:30,120 --> 00:09:32,000 I THINK WE CAN LEARN MUCH MORE 175 00:09:32,000 --> 00:09:36,640 LOOKING FOR THE COMMON 176 00:09:36,640 --> 00:09:39,200 PERSISTENT PAIN CONDITION, LIKE 177 00:09:39,200 --> 00:09:42,480 FIBROMYALGIA, THOSE THAT AFFECT 178 00:09:42,480 --> 00:09:46,800 OFTIO ARTHRITIS, THOSE HAD WHICH 179 00:09:46,800 --> 00:09:49,200 ARE HIT REALLY HIGH PERCENT OF 180 00:09:49,200 --> 00:09:52,320 THE POPULATION, IN FACT 20% OF 181 00:09:52,320 --> 00:09:54,920 AMERICANS REPORT CHRONIC PAIN 182 00:09:54,920 --> 00:09:57,880 AND OF COURSE THEY CAN STUDY 183 00:09:57,880 --> 00:10:07,280 THIS FROM GENETIC MARKERS. 184 00:10:07,280 --> 00:10:13,040 AND WE SEE THIS RIGHT NOW WHEN 185 00:10:13,040 --> 00:10:14,840 WE DEVELOP ALGORITHMS OF HUMAN 186 00:10:14,840 --> 00:10:16,240 GENETICS, IF WE CAN INTEGRATE 187 00:10:16,240 --> 00:10:18,640 THIS KNOWLEDGE ON ALL DIFFERENT 188 00:10:18,640 --> 00:10:19,800 LEVEL OF [INDISCERNIBLE] EXISTS 189 00:10:19,800 --> 00:10:25,760 THIS, IS WHERE WE CAN COME TO 190 00:10:25,760 --> 00:10:28,800 THE MOST MULTIDIMENSIONAL 191 00:10:28,800 --> 00:10:32,120 FEATURE BASED ON THIS PAIN AND 192 00:10:32,120 --> 00:10:35,120 THE PROCESSES LIKE WHAT'S BEEN 193 00:10:35,120 --> 00:10:38,280 HAPPENING IN ONCOLOGY WHICH IS 194 00:10:38,280 --> 00:10:45,400 PROBABLY RELATED FIELD IN THIS 195 00:10:45,400 --> 00:10:45,800 APPROACH. 196 00:10:45,800 --> 00:10:46,720 SO [INDISCERNIBLE], SO FIRST I 197 00:10:46,720 --> 00:10:49,760 HOPE I CONVINCE YOU THAT WE 198 00:10:49,760 --> 00:10:53,560 DON'T KNOW MUCH ABOUT 199 00:10:53,560 --> 00:10:58,600 PATHOPHYSIOLOGY OF CHRONIC PAIN 200 00:10:58,600 --> 00:11:00,400 AND THE OMICS-WIDE APPROACH IS A 201 00:11:00,400 --> 00:11:01,040 NEW DEVELOPMENT. 202 00:11:01,040 --> 00:11:07,120 SO I WILL TELL YOU A FEW 203 00:11:07,120 --> 00:11:08,480 STORIES, AND 1 IS ON THE LEVEL 204 00:11:08,480 --> 00:11:11,920 OF GENOME AND THIS IS GENOME 205 00:11:11,920 --> 00:11:16,960 WIDE ANALYSIS WHICH IDENTIFIED 206 00:11:16,960 --> 00:11:21,320 AXO-GENESIS IN CHRONIC 207 00:11:21,320 --> 00:11:22,160 OVERLAPPING PAIN CONDITIONS. 208 00:11:22,160 --> 00:11:23,920 SO THIS STUDY AS JUST BEEN 209 00:11:23,920 --> 00:11:31,080 PUBLISHED IN BRAIN, IN THE FIRST 210 00:11:31,080 --> 00:11:35,000 AND SO THIS BOOK HAS BEEN 211 00:11:35,000 --> 00:11:36,520 PUBLISHED BY [INDISCERNIBLE], BY 212 00:11:36,520 --> 00:11:41,600 THE WAY, I WON'T HAVE THE FINAL 213 00:11:41,600 --> 00:11:44,800 THANK YOU SLIDE WHERE I WILL 214 00:11:44,800 --> 00:11:45,680 PUT--ATTEMPT TO RECOGNIZED ALL 215 00:11:45,680 --> 00:11:47,680 THE PEOPLE WHO HELPED ME WITH MY 216 00:11:47,680 --> 00:11:50,200 PROJECT DURING MY TALK. 217 00:11:50,200 --> 00:11:57,280 SO HERE'S THE PROJECT PAPER THAT 218 00:11:57,280 --> 00:11:59,320 HAS BEEN PUBLISHED 219 00:11:59,320 --> 00:12:04,520 [INDISCERNIBLE] AND STUDIED IN 220 00:12:04,520 --> 00:12:10,600 THIS CASE, PAIN IN UK BIOBANK. 221 00:12:10,600 --> 00:12:18,880 SO THE UK BIOBANK IS THIS 222 00:12:18,880 --> 00:12:21,320 UNBELIEVABLE BIOBANK--MULTIPLE, 223 00:12:21,320 --> 00:12:24,400 MULTIPLE PHENOTYPES INCLUDING 224 00:12:24,400 --> 00:12:27,600 PAIN PHENOTYPE AND GWASS AND 225 00:12:27,600 --> 00:12:31,520 MANY OTHER CLINICAL PHENOTYPES, 226 00:12:31,520 --> 00:12:33,600 AND MORE COMMON. 227 00:12:33,600 --> 00:12:37,360 SO IN UK BIOBANK WE USE 228 00:12:37,360 --> 00:12:38,480 QUESTIONNAIRE WHICH ASKED PEOPLE 229 00:12:38,480 --> 00:12:41,280 DID HAVE YOU PAIN IN THE LAST 230 00:12:41,280 --> 00:12:43,320 MONTHS THAT IMPAIRED YOUR USUAL 231 00:12:43,320 --> 00:12:44,040 DAILY ACTIVITY? 232 00:12:44,040 --> 00:12:45,800 AND IF PEOPLE SAID YES, THE 233 00:12:45,800 --> 00:12:47,160 SECOND QUESTION WAS HAVE YOU HAD 234 00:12:47,160 --> 00:12:50,720 THIS PAIN FOR MORE THAN 3 235 00:12:50,720 --> 00:12:51,080 MONTHS? 236 00:12:51,080 --> 00:12:55,600 SO YOU CAN SEE, PEOPLE CAN 237 00:12:55,600 --> 00:12:56,760 REPORT PAIN IN DIFFERENT BODY 238 00:12:56,760 --> 00:12:57,000 SITE. 239 00:12:57,000 --> 00:13:03,080 THIS IS NUMBER OF CASES WE HAVE. 240 00:13:03,080 --> 00:13:11,600 SO FIRST WE DID THIS GENETIC 241 00:13:11,600 --> 00:13:12,200 CORRELATION BETWEEN DIFFERENT 242 00:13:12,200 --> 00:13:15,120 BODY TYPE AND WE ALSO KNOW FROM 243 00:13:15,120 --> 00:13:16,840 THE EPIDEMIOLOGICAL STUDY WHICH 244 00:13:16,840 --> 00:13:21,520 WAS REPRODUCED HERE IN THE 245 00:13:21,520 --> 00:13:25,000 [INDISCERNIBLE], THAT IT IS A 246 00:13:25,000 --> 00:13:26,400 HUGE OVERLAP BETWEEN DIFFERENT 247 00:13:26,400 --> 00:13:30,800 CHRONIC PAIN CONDITION. 248 00:13:30,800 --> 00:13:33,040 SO IN FACT HAVING 1 PAIN 249 00:13:33,040 --> 00:13:35,440 CONDITION, IS THE RISK PREDICTOR 250 00:13:35,440 --> 00:13:37,040 TO HAVE OTHER PAIN CONDITION. 251 00:13:37,040 --> 00:13:39,600 SO HERE IN THE ORANGE WE SEE 252 00:13:39,600 --> 00:13:42,680 VERY SIGNIFICANT GENETIC 253 00:13:42,680 --> 00:13:45,720 RELATION, ALSO BETWEEN DIFFERENT 254 00:13:45,720 --> 00:13:46,800 CHRONIC PAIN CONDITION, SOME OF 255 00:13:46,800 --> 00:13:50,520 WHICH IS A RISING QUESTION, WHY 256 00:13:50,520 --> 00:13:50,760 SO? 257 00:13:50,760 --> 00:13:53,840 IS IS IT THIS OVERLAPPING 258 00:13:53,840 --> 00:13:56,560 CHRONIC PAIN CONDITION IS A 259 00:13:56,560 --> 00:13:59,400 SEPARATE BEAST, MAYBE IT'S A 260 00:13:59,400 --> 00:14:05,800 SEPARATE DISEASE WHICH WE CAN 261 00:14:05,800 --> 00:14:07,000 STUDY. 262 00:14:07,000 --> 00:14:09,320 IN THIS GENETIC OF PEOPLE WITH 263 00:14:09,320 --> 00:14:10,600 OVERLAPPING PAIN CONDITION, CAN 264 00:14:10,600 --> 00:14:14,400 LEAD US TO UNDERSTAND THIS 265 00:14:14,400 --> 00:14:14,760 PATHOPHYSIOLOGY. 266 00:14:14,760 --> 00:14:18,880 SO FIRST WE DID THIS 267 00:14:18,880 --> 00:14:19,840 [INDISCERNIBLE], WHAT WE MIGHT 268 00:14:19,840 --> 00:14:23,640 ESTABLISH RIGHT NOW IN GWAS, SO 269 00:14:23,640 --> 00:14:25,120 THIS IS MANAT AN PLOT, ACTUALLY 270 00:14:25,120 --> 00:14:26,720 THIS IS SO CALLED 271 00:14:26,720 --> 00:14:27,640 [INDISCERNIBLE] PLOT BECAUSE YOU 272 00:14:27,640 --> 00:14:31,200 CAN SEE BOTH UP AND DOWN AND 273 00:14:31,200 --> 00:14:35,880 HERE IS ALL THE SINGLE VARIANTS, 274 00:14:35,880 --> 00:14:37,280 EVERYTHING WHICH IS THE 275 00:14:37,280 --> 00:14:37,920 [INDISCERNIBLE], THE LINE, I 276 00:14:37,920 --> 00:14:40,800 DON'T KNOW IF YOU CAN JOIN THIS, 277 00:14:40,800 --> 00:14:48,440 AND HERE WE HAVE SAME SCAN FOR 278 00:14:48,440 --> 00:14:50,440 THE GENE, SO YOU SEE 1 SINGLE 279 00:14:50,440 --> 00:14:53,920 SIDE, THIS IS NOT MUCH GENETIC, 280 00:14:53,920 --> 00:14:58,200 OKAY, THERE WAS 1 LOCITE WHICH 281 00:14:58,200 --> 00:15:00,400 WAS SIGNIFICANT EPIGENOME WIDE 282 00:15:00,400 --> 00:15:02,200 LEVEL, BUT IF WE KNEW THAT 283 00:15:02,200 --> 00:15:05,080 MULTISITE PAIN, WHEN PEOPLE 284 00:15:05,080 --> 00:15:08,400 REPORT 2 OR MORE CHRONIC PAIN 285 00:15:08,400 --> 00:15:09,840 SITE, VERSUS PEOPLE WHO DON'T 286 00:15:09,840 --> 00:15:11,560 REPORT ANY PAIN, CAN YOU SEE NOW 287 00:15:11,560 --> 00:15:13,800 THERE IS VERY SUBSTANTIAL AND 288 00:15:13,800 --> 00:15:15,680 GENETIC COMPONENT ON THE LEVEL 289 00:15:15,680 --> 00:15:21,000 OF SNPs, AND EVEN MORE ON THE 290 00:15:21,000 --> 00:15:21,760 LEVEL OF GENES. 291 00:15:21,760 --> 00:15:24,200 SO THE NEXT ASKED QUESTION, IF 292 00:15:24,200 --> 00:15:26,400 WE CAN IDENTIFY THIS GENETIC 293 00:15:26,400 --> 00:15:38,160 VARIANT, WHICH IS UNIQUE FOR 294 00:15:38,160 --> 00:15:39,000 MULTISITE PAIN, PLEIOTROPIC, 295 00:15:39,000 --> 00:15:40,480 MEANS MAYBE THERE IS MORE SIDES 296 00:15:40,480 --> 00:15:43,360 BAWSES THE SAME GENE YOU KNOW MY 297 00:15:43,360 --> 00:15:51,840 FAVORITE TMT IS AT LEAST FOR 298 00:15:51,840 --> 00:15:54,440 [INDISCERNIBLE] PAIN AND FOR 299 00:15:54,440 --> 00:15:58,600 HEADACHE AND SO IN THE SINGLE 300 00:15:58,600 --> 00:16:00,480 ROW THERE'S NOT ENOUGH FOR US TO 301 00:16:00,480 --> 00:16:02,560 SEE BUT WHEN IT COMES TOGETHER, 302 00:16:02,560 --> 00:16:05,400 WE START TO SEE MORE 303 00:16:05,400 --> 00:16:06,680 SIGNIFICANCE. 304 00:16:06,680 --> 00:16:11,800 WE HAVE SUCH UNIQUE THAT WE SEE 305 00:16:11,800 --> 00:16:12,960 SOME VARIANT UNIQUE ONLY FOR ALL 306 00:16:12,960 --> 00:16:14,040 OF THE PAIN CONDITION BUT YOU 307 00:16:14,040 --> 00:16:17,320 DON'T SEE ANY OF THIS FOR THE 308 00:16:17,320 --> 00:16:17,760 SINGLE SITE PAIN. 309 00:16:17,760 --> 00:16:22,200 AND IT WAS MAINLY--IT WAS MAINLY 310 00:16:22,200 --> 00:16:27,360 PLEIOTROAPIC BUT IT WAS VERY 311 00:16:27,360 --> 00:16:27,960 UNIQUE. 312 00:16:27,960 --> 00:16:30,160 THE MOST VARIANTS WE HAD FROM 313 00:16:30,160 --> 00:16:33,600 THIS GENE CALLED DCC WHICH IS 314 00:16:33,600 --> 00:16:34,520 [INDISCERNIBLE] AND WILL BE 315 00:16:34,520 --> 00:16:36,000 IMPORTANT A LITTLE BIT LATER IN 316 00:16:36,000 --> 00:16:37,080 MY TALK. 317 00:16:37,080 --> 00:16:39,720 SO BECAUSE NEXT AFTER WE DID THE 318 00:16:39,720 --> 00:16:46,520 GWAS, WE DID AFTER THIS, WE HAD 319 00:16:46,520 --> 00:16:47,560 THE [INDISCERNIBLE], MEANS WE 320 00:16:47,560 --> 00:16:50,600 TOOK ALL OF THIS FOR THE 321 00:16:50,600 --> 00:16:52,800 INFORMATION FOR GENOME WIDE 322 00:16:52,800 --> 00:16:57,160 ASSOCIATION STUDIES AND WE MAP 323 00:16:57,160 --> 00:17:00,000 IT TO EXPRESSION TO DIFFERENT 324 00:17:00,000 --> 00:17:00,360 HUMAN TISSUES. 325 00:17:00,360 --> 00:17:04,160 SO HERE YOU CAN SEE, 326 00:17:04,160 --> 00:17:06,080 ACTUALLY--IT'S NOT ALL OF THEM, 327 00:17:06,080 --> 00:17:11,040 MAP IT TO ALL PUBLICLY AVAILABLE 328 00:17:11,040 --> 00:17:12,880 TRANSCRIPT O--METABOLIZEDDICS OF 329 00:17:12,880 --> 00:17:13,800 TISSUES, AND SURPRISINGLY OR NOT 330 00:17:13,800 --> 00:17:19,280 ISSUES THE ONLY DIG 95 CANC, - 331 00:17:19,280 --> 00:17:26,160 -SIGNIFICANCE, SO FIRST WE 332 00:17:26,160 --> 00:17:30,280 FOLLOW THE SINGLE SIDE IN 333 00:17:30,280 --> 00:17:31,440 FORWARD LAPPING CONDITION, AND 334 00:17:31,440 --> 00:17:33,400 THE CENTRAL NERVOUS SYSTEM IS 335 00:17:33,400 --> 00:17:38,000 THE 1, BUT VERY ROBUSTLY, TO 336 00:17:38,000 --> 00:17:59,400 THIS GWAS, SO, WOULD WE SEE IS 337 00:17:59,400 --> 00:18:00,080 UNIQUE--BECAUSE WE DIDN'T HAVE 338 00:18:00,080 --> 00:18:01,080 THE TISSUE ON THIS. 339 00:18:01,080 --> 00:18:07,720 SO NEXT WHAT WE DID WAS THE TOP 340 00:18:07,720 --> 00:18:09,000 SNP-BASED PATHWAYS OF MULTISITE 341 00:18:09,000 --> 00:18:09,760 PAIN FROM GWAS STUDY. 342 00:18:09,760 --> 00:18:14,320 SO YOU CAN SEE THE PATHWAY WAS 343 00:18:14,320 --> 00:18:16,040 OVERLAYING, BIOLOGICALLY IT WAS 344 00:18:16,040 --> 00:18:17,720 CELL PROJECTION WITHIN ACTIVATED 345 00:18:17,720 --> 00:18:23,720 SIGNALING PATHWAY IN REGULATION 346 00:18:23,720 --> 00:18:25,240 EVER NEUROGENESIS. 347 00:18:25,240 --> 00:18:27,200 SO THIS WAS ALL DRIVEN BY THE 348 00:18:27,200 --> 00:18:34,520 ACTIVATION OF THE SIGNALING 349 00:18:34,520 --> 00:18:37,040 PATHWAY. 350 00:18:37,040 --> 00:18:39,680 WHAT IS THE AXONAL GUIDANCE, 351 00:18:39,680 --> 00:18:42,200 WELL, DURING NEURONAL 352 00:18:42,200 --> 00:18:48,480 DEVELOPMENT, AXONS ARE GUIDED BY 353 00:18:48,480 --> 00:18:51,840 AND HERE WE CAN SEE THE 354 00:18:51,840 --> 00:18:54,600 MOLECULES WHICH INVOLVED IN THIS 355 00:18:54,600 --> 00:19:00,520 SO YOU CAN SEE THAT THIS 356 00:19:00,520 --> 00:19:07,600 POSITIVE ATTRACT ANT FOR 357 00:19:07,600 --> 00:19:09,600 MUTATING. 358 00:19:09,600 --> 00:19:10,240 FOR AXONAL GUIDANCE USUALLY 359 00:19:10,240 --> 00:19:13,240 SOUGHT IN THE BRAIN DEVELOPMENT, 360 00:19:13,240 --> 00:19:15,840 AXONAL GUIDANCE HAVE ALSO HAVE 361 00:19:15,840 --> 00:19:17,760 BEEN MINERALS BEYOND AXONAL 362 00:19:17,760 --> 00:19:24,440 GUIDANCE, SO, FOR EXAMPLE, FOR 363 00:19:24,440 --> 00:19:25,600 SYNAPTIC PLASTICITY, AXONAL 364 00:19:25,600 --> 00:19:30,840 GUIDANCE WAS ALSO IMPLEMENTED 365 00:19:30,840 --> 00:19:33,920 GREATLY IN THE CONTINUATION--WAS 366 00:19:33,920 --> 00:19:36,760 IMPLEMENTED IN THE LATE ONSET 367 00:19:36,760 --> 00:19:40,400 BRAIN DISORDER SUCH AS 368 00:19:40,400 --> 00:19:41,720 NEURODEGENERATIVE DISEASES. 369 00:19:41,720 --> 00:19:47,440 SO, OKAY, BRAIN, YES, SO THIS IS 370 00:19:47,440 --> 00:19:48,440 AXONAL GUIDANCE. 371 00:19:48,440 --> 00:19:55,040 SO DCC, SO WE WANTED TO MOVE IN 372 00:19:55,040 --> 00:19:58,960 THE BRAIN OF THE PEOPLE WITH THE 373 00:19:58,960 --> 00:20:00,600 CHRONIC PAIN CONDITION, IN THIS 374 00:20:00,600 --> 00:20:10,040 STUDY HASN'T BEEN DONE BY 375 00:20:10,040 --> 00:20:11,840 [INDISCERNIBLE] AT Mc GILL, 376 00:20:11,840 --> 00:20:16,000 AND WE USE AGAIN BIOBANK, IT'S 377 00:20:16,000 --> 00:20:17,280 UNBELIEVABLE HOW MUCH RESOURCES 378 00:20:17,280 --> 00:20:20,560 WE HAVE FOR BRAIN IMAGING IN UK 379 00:20:20,560 --> 00:20:20,800 BIOBANK. 380 00:20:20,800 --> 00:20:27,640 SO FIRST WHAT WE DID HERE IS WE 381 00:20:27,640 --> 00:20:30,440 LOOK FOR EXPRESSION OF DCC IN 382 00:20:30,440 --> 00:20:32,320 HUMAN BRAIN AND YOU CAN SEE THAT 383 00:20:32,320 --> 00:20:35,400 IT IS ABSOLUTELY THE HIGHEST 384 00:20:35,400 --> 00:20:37,400 EXPRESS IN SUBCORTICAL REGION OF 385 00:20:37,400 --> 00:20:38,960 THE SUBACCOUNTS AND HIPAA 386 00:20:38,960 --> 00:20:40,080 COUNTS. 387 00:20:40,080 --> 00:20:44,440 IN THIS REGION, IS THAT 1 WHICH 388 00:20:44,440 --> 00:20:45,960 IS USUALLY KNOWN FOR CORTICAL 389 00:20:45,960 --> 00:20:53,240 INDEX SYSTEM WHICH IS INVOLVED 390 00:20:53,240 --> 00:20:54,200 IN MOTIVATION BUT ALSO 391 00:20:54,200 --> 00:21:02,440 INDICATION OF GROWING PAIN. 392 00:21:02,440 --> 00:21:03,760 SOY THEN WE WERE THINKING ABOUT 393 00:21:03,760 --> 00:21:07,560 WHAT WE CAN MOVE TO AXONAL 394 00:21:07,560 --> 00:21:12,360 GEPMENT AND IF --DEVELOPMENT. 395 00:21:12,360 --> 00:21:15,560 AND IF YOU LOOK AT THE WHITE 396 00:21:15,560 --> 00:21:17,800 MATTER, ALSO BECAUSE WE COULD DO 397 00:21:17,800 --> 00:21:22,600 THIS IN UK BIOBANK IN USING THIS 398 00:21:22,600 --> 00:21:24,360 [INDISCERNIBLE] PATIENT. 399 00:21:24,360 --> 00:21:26,320 SO THIS SPECIAL ORIENTATION IS A 400 00:21:26,320 --> 00:21:31,200 KIND OF A MIX OF SPECIAL 401 00:21:31,200 --> 00:21:35,320 ORGANIZATION OF MATRIX, OF 402 00:21:35,320 --> 00:21:35,600 AXONS. 403 00:21:35,600 --> 00:21:43,200 AND THEY LOOK TO SEVERAL OF THEM 404 00:21:43,200 --> 00:21:52,040 WHICH IS CONNECTING THE 405 00:21:52,040 --> 00:21:55,400 SUBCORTICAL LIMBIC REGION CORTEX 406 00:21:55,400 --> 00:22:00,440 AND WE SAW THAT UNCINATE 407 00:22:00,440 --> 00:22:02,680 FASCICULUS IS CONNECT TO THE 408 00:22:02,680 --> 00:22:09,080 STRUCTURES WAS REALLY GREATLY 409 00:22:09,080 --> 00:22:12,160 DIFFERENT IN THEIR O. D., 410 00:22:12,160 --> 00:22:14,200 BETWEEN PEOPLE WHO HAVE NO PAIN 411 00:22:14,200 --> 00:22:17,200 AT ALL AND HAVE MULTISITE PAIN 412 00:22:17,200 --> 00:22:19,160 OR HAVE ONLY SINGLE SITE PAIN 413 00:22:19,160 --> 00:22:23,440 AND YOU SEE THERE'S THIS POINT 414 00:22:23,440 --> 00:22:23,960 IN THE RELATIONSHIP. 415 00:22:23,960 --> 00:22:41,880 SO AS A CONCLUSION 1 TO MY FIRST 416 00:22:41,880 --> 00:22:43,400 STORY, THERE IS--SO THEY KNOW 417 00:22:43,400 --> 00:22:51,800 ALL CONFUSION, THE RESULT OF 418 00:22:51,800 --> 00:22:54,960 GWAS, STUDIES CAN BE USED FOR 419 00:22:54,960 --> 00:22:56,080 UNDERSTANDING OF MOLECULAR 420 00:22:56,080 --> 00:22:58,600 PATHOPHYSIOLOGY OF CHRONIC PAIN. 421 00:22:58,600 --> 00:23:01,520 WE CAN USE THIS TO DECIDE THE 422 00:23:01,520 --> 00:23:01,800 IMPAIRMENT. 423 00:23:01,800 --> 00:23:03,200 BY THE WAY, MAYBE I SHOULD SAY 424 00:23:03,200 --> 00:23:06,760 HERE THAT IT'S NOT ONLY THAT O. 425 00:23:06,760 --> 00:23:08,840 D. WAS DIFFERENT BETWEEN PAIN 426 00:23:08,840 --> 00:23:10,280 AND MULTISITE, BUT WHAT THIS 427 00:23:10,280 --> 00:23:12,200 MEANS IS HIGHER, IT DOESN'T MEAN 428 00:23:12,200 --> 00:23:16,760 IT'S HIGHER, IT MEANS THEY'RE 429 00:23:16,760 --> 00:23:17,800 NOT [INDISCERNIBLE], SO THERE 430 00:23:17,800 --> 00:23:23,520 HAS NOT BEEN GROWING IN THE NICE 431 00:23:23,520 --> 00:23:27,200 ORGANIZED PART. 432 00:23:27,200 --> 00:23:30,080 AND SO, WHAT WE SEE HERE THAT 433 00:23:30,080 --> 00:23:31,200 ALTHOUGH AXONAL GUIDANCE CAN BE 434 00:23:31,200 --> 00:23:42,600 OF COURSE AFFECTED DURING OUR 435 00:23:42,600 --> 00:23:43,720 LIFE [INDISCERNIBLE], PEOPLE CAN 436 00:23:43,720 --> 00:23:45,400 ALSO HAVE OPTIMAL AXONAL 437 00:23:45,400 --> 00:23:50,240 GUIDANCE ROLES, SO PEOPLE HAVE 438 00:23:50,240 --> 00:23:51,160 [INDISCERNIBLE] FOR 439 00:23:51,160 --> 00:23:52,200 PREDEVELOPING PAIN CONDITION. 440 00:23:52,200 --> 00:23:56,720 SO NOW THAT BRINGS US TO THE 441 00:23:56,720 --> 00:23:59,160 SECOND EXAMPLE ABOUT THE OMICS 442 00:23:59,160 --> 00:23:59,880 EPITHELIALIGRATION AND THIS TIME 443 00:23:59,880 --> 00:24:04,480 I WILL TELL YOU STORY ABOUT THE 444 00:24:04,480 --> 00:24:07,200 UNBIAS IMMUNE PROFILING THAT 445 00:24:07,200 --> 00:24:12,960 REVEALS A NATURAL KILLER CELL 446 00:24:12,960 --> 00:24:17,600 PERIPHERAL NERVE AXIS IN 447 00:24:17,600 --> 00:24:18,240 FIBROMYALGIA PATIENTS. 448 00:24:18,240 --> 00:24:22,000 SO IN THIS STUDY, WE RECORDED 449 00:24:22,000 --> 00:24:23,280 FIBRO MYALGIA PATIENTS AND 450 00:24:23,280 --> 00:24:25,000 STUDIED BLOOD AND FINDING 451 00:24:25,000 --> 00:24:27,240 FUNCTIONAL SAVING AND GENETIC 452 00:24:27,240 --> 00:24:27,600 AND TRANSCRIPT 453 00:24:27,600 --> 00:24:28,400 O--METABOLIZEDDICS IN THE SYSTEM 454 00:24:28,400 --> 00:24:32,200 AND THEN ALSO ANALYZED IN 455 00:24:32,200 --> 00:24:33,920 ANOTHER INDEPENDENT COHORT AND 456 00:24:33,920 --> 00:24:34,800 SKIN BIOPSY. 457 00:24:34,800 --> 00:24:36,840 THIS HAS ALSO BEEN JUST 458 00:24:36,840 --> 00:24:42,400 PUBLISHED AND I THINK IT'S JUST 459 00:24:42,400 --> 00:24:45,680 ACCEPTED IN PAIN AND HAS BEEN 460 00:24:45,680 --> 00:24:51,240 [INDISCERNIBLE] AND GRADUATE 461 00:24:51,240 --> 00:24:51,800 STUDENT [INDISCERNIBLE]. 462 00:24:51,800 --> 00:24:58,040 SO FIRST JUST THE RESULT OF THE 463 00:24:58,040 --> 00:24:59,320 EFFORT WE FOUND 2 CELL TYPES 464 00:24:59,320 --> 00:25:01,680 THAT WERE DIFFERENT BETWEEN 465 00:25:01,680 --> 00:25:02,440 CASES IN CONTROL. 466 00:25:02,440 --> 00:25:08,560 IT WAS A B-CELLS AND NK CELLS. 467 00:25:08,560 --> 00:25:10,200 THE MOST SIGNIFICANT--IN THE WAY 468 00:25:10,200 --> 00:25:13,120 THAT B-CELLS WAS PLACED IN FIBRO 469 00:25:13,120 --> 00:25:17,240 MYALGIA PATIENTS AND NK CELLS 470 00:25:17,240 --> 00:25:17,920 WAS BASICALLY DEPLETED. 471 00:25:17,920 --> 00:25:19,880 AND WE FOUND THIS DIFFERENCE 472 00:25:19,880 --> 00:25:21,160 REALLY CAME FROM NK CELLS AND 473 00:25:21,160 --> 00:25:23,760 THIS IS WHAT WE FOLLOW. 474 00:25:23,760 --> 00:25:28,360 AND IN FACT MOST NK CELLS AND 475 00:25:28,360 --> 00:25:30,000 B-CELLS CONTRIBUTION TO FIBRO 476 00:25:30,000 --> 00:25:32,320 MYALGIA WAS PROBABLY NOT THE 477 00:25:32,320 --> 00:25:36,360 PRIMARY HYPOTHESIS OF OURS OR WE 478 00:25:36,360 --> 00:25:38,000 NEED PEOPLE TO STUDY PAIN AND 479 00:25:38,000 --> 00:25:41,000 ESPECIALLY IN NK CELLS SO THIS 480 00:25:41,000 --> 00:25:42,760 IS WHY THERE WAS GREAT INTEREST 481 00:25:42,760 --> 00:25:47,360 IN THIS CELL TYPE. 482 00:25:47,360 --> 00:25:54,000 SO NEXT WE CHARACTERIZE THIS NK 483 00:25:54,000 --> 00:25:57,320 CELLS AND WHAT WE SAW IN IT NK 484 00:25:57,320 --> 00:26:01,000 CELLS, THAT THEY HAD DECREASED, 485 00:26:01,000 --> 00:26:02,760 SO FIRST EXPRESSION OVER NK 486 00:26:02,760 --> 00:26:09,720 CELLS, YOU KNOW AS YOU CAN SEE 487 00:26:09,720 --> 00:26:14,280 BY CD16, CD8-6 AND CD96 SURFACE 488 00:26:14,280 --> 00:26:14,600 MARKER. 489 00:26:14,600 --> 00:26:18,520 BUT, WE HAVE INCREASED SOME FREE 490 00:26:18,520 --> 00:26:29,440 EXPRESSION OF THE EVALUATION 491 00:26:29,440 --> 00:26:32,800 MARKER, CD107A AND THEN THE 492 00:26:32,800 --> 00:26:36,240 [INDISCERNIBLE] MARKER. 493 00:26:36,240 --> 00:26:39,200 SO BASICALLY IT'S A VERY TYPICAL 494 00:26:39,200 --> 00:26:45,200 MARKER, THIS IS VERY TYPICAL 495 00:26:45,200 --> 00:26:47,280 PICTURE OF CELL EXHAUSTION 496 00:26:47,280 --> 00:26:47,960 PHENOTYPE. 497 00:26:47,960 --> 00:26:50,920 SO WE COMPUTED THE DOWNWARD 498 00:26:50,920 --> 00:26:53,400 CELLS BY EXHAUSTED IF FIBRO 499 00:26:53,400 --> 00:27:00,280 MYALGIA PATIENTS. 500 00:27:00,280 --> 00:27:03,000 SO REMEMBER THEY--YEAH, THEY 501 00:27:03,000 --> 00:27:04,120 ACTIVATE. 502 00:27:04,120 --> 00:27:07,480 SO THERE IS SOME--THEY'VE BEEN 503 00:27:07,480 --> 00:27:12,120 DEGRANNULATED SO THEY HAVE HIGH 504 00:27:12,120 --> 00:27:13,200 REGULATION VIA ABSORPTION. 505 00:27:13,200 --> 00:27:20,200 SO DEEP NK ACTIVATION IS STUDIED 506 00:27:20,200 --> 00:27:24,360 AND THEN WE USE 2 DIFFERENT 507 00:27:24,360 --> 00:27:26,600 [INDISCERNIBLE], SO HLA MINUS 508 00:27:26,600 --> 00:27:28,760 ASSAY WHICH ACTUALLY OR WHICH 509 00:27:28,760 --> 00:27:30,960 STUDY DID FUNCTIONAL CYTOTOXIC 510 00:27:30,960 --> 00:27:35,920 POTENTIAL OF THE NK CELLS AND SO 511 00:27:35,920 --> 00:27:50,040 WE ALSO DID THE ADNKA ASSAY, 512 00:27:50,040 --> 00:27:51,640 WHICH--BECAUSE OUR CELLS ARE 513 00:27:51,640 --> 00:27:53,160 EXHAUSTED THEY WILL NOT BE 514 00:27:53,160 --> 00:27:53,400 ACTIVE. 515 00:27:53,400 --> 00:27:56,400 BUT IN FACT IT WAS HAPPY 516 00:27:56,400 --> 00:27:59,280 RESPONSIVE, THERE WAS HAPPIER 517 00:27:59,280 --> 00:28:03,080 RESPONSIVE IN HLA, ASSAY, FOR 518 00:28:03,080 --> 00:28:10,680 THIS CCL4, WHICH IS ALSO 519 00:28:10,680 --> 00:28:11,960 MACROPHAGE INFLAMMATORY PROTEIN 520 00:28:11,960 --> 00:28:16,800 1 BETTER, HAS BEEN MUCH MORE--BY 521 00:28:16,800 --> 00:28:19,720 THE WAY, THE BASE LINE FIBRO 522 00:28:19,720 --> 00:28:21,200 MYALGIA IN CONTROL, THEY WERE 523 00:28:21,200 --> 00:28:22,040 NOT DIFFERENT, RIGHT? 524 00:28:22,040 --> 00:28:24,640 SO ONLY AFTER ACTIVATION, YOU 525 00:28:24,640 --> 00:28:28,760 KNOW QUITE A BIG DIFFERENCE IN 526 00:28:28,760 --> 00:28:30,240 ALPHA WHICH FIBRO MYALGIA 527 00:28:30,240 --> 00:28:36,800 PATIENT HAS BROUGHT MUCH MORE 528 00:28:36,800 --> 00:28:42,240 NUMEROUSLY, SECRETING BUT ALSO 529 00:28:42,240 --> 00:28:49,960 CD17 WHICH IS ALSO HYPER 530 00:28:49,960 --> 00:28:50,360 RESPONSIVE MARKER. 531 00:28:50,360 --> 00:28:54,800 SO AS YOU SEE THE NK, DID IT 532 00:28:54,800 --> 00:28:58,400 PRACTICES DUCE ANY DIFFERENCE IN 533 00:28:58,400 --> 00:28:58,600 CELLS? 534 00:28:58,600 --> 00:29:01,240 BUT SAYING IT WELL, IT'S 535 00:29:01,240 --> 00:29:03,440 PROBABLY BECAUSE WE SAW THAT 536 00:29:03,440 --> 00:29:10,360 CD16 ARE NK CELL IN FIBRO 537 00:29:10,360 --> 00:29:13,120 MYALGIA CASES, HAVE MORE 538 00:29:13,120 --> 00:29:16,200 EXPRESSION OF CD16, CD16 WAS 539 00:29:16,200 --> 00:29:18,600 PORTION OF ANTIBODY IS CRUCIAL 540 00:29:18,600 --> 00:29:20,800 IN MEDIATING ANTIBODY DEPENDENT 541 00:29:20,800 --> 00:29:22,560 NK CELL ACTIVATION, SO YES, 542 00:29:22,560 --> 00:29:26,520 THERE WASN'T REALLY ABLE TO 543 00:29:26,520 --> 00:29:34,920 RESPOND TO ANTIBODY DEPENDENT 544 00:29:34,920 --> 00:29:35,720 ASSAY. 545 00:29:35,720 --> 00:29:38,320 BUT AGAIN, [INDISCERNIBLE] WAS 546 00:29:38,320 --> 00:29:40,320 MUCH MORE TOXIC AND WAS HYPER 547 00:29:40,320 --> 00:29:41,960 RESPONSIVE, SO THE NEXT CAME 548 00:29:41,960 --> 00:29:45,800 FROM FOOD GENETICS AND FOOD 549 00:29:45,800 --> 00:29:49,960 TRANSCRIPT OMICS, WHEN WE DID 550 00:29:49,960 --> 00:29:51,520 FULL RNASEQ, OF FIBRO MYALGIA 551 00:29:51,520 --> 00:29:55,080 PATIENTS BUT WE ALSO DID GENOME 552 00:29:55,080 --> 00:29:57,160 WIDE ANALYSIS OF FIBRO MYALGIA 553 00:29:57,160 --> 00:30:01,200 PATIENT, IN FACT IN BOTH BACK IN 554 00:30:01,200 --> 00:30:03,920 THE UK BIOBANK AND SO IN THIS 555 00:30:03,920 --> 00:30:06,000 CASE, WE DID ANALYSIS, AND WHEN 556 00:30:06,000 --> 00:30:10,320 WE DID THE [INDISCERNIBLE] 557 00:30:10,320 --> 00:30:12,880 IMMUNE CELLS IN CELL ACTIVATION 558 00:30:12,880 --> 00:30:14,240 AND REGULATION. 559 00:30:14,240 --> 00:30:18,560 YOU CAN SEE MOST TRANSCRIPT 560 00:30:18,560 --> 00:30:20,040 OMICS ARE GENETIC. 561 00:30:20,040 --> 00:30:22,120 THE ONLY SOLUTION YOU CAN HEAT 562 00:30:22,120 --> 00:30:24,840 IF YOU HAD IN WORSE CASE WAS 563 00:30:24,840 --> 00:30:26,720 ABOUT SELECT NK CELL ACTIVATION 564 00:30:26,720 --> 00:30:30,480 AND REGULATION OF NK CELLS. 565 00:30:30,480 --> 00:30:34,360 AGAIN, NOT SOMETHING WHICH WE 566 00:30:34,360 --> 00:30:34,600 EXPECT. 567 00:30:34,600 --> 00:30:41,560 SO THEN WE WERE THINKING LIKE, 568 00:30:41,560 --> 00:30:44,240 WHAT NK CELLS CAN DO IN FIBRO 569 00:30:44,240 --> 00:30:46,560 MYALGIA, SO THEN THE HYPOTHESIS 570 00:30:46,560 --> 00:30:50,400 COME FROM 2 LINES, SO 1 571 00:30:50,400 --> 00:30:53,160 IS--ACTUALLY SEMINOLE 572 00:30:53,160 --> 00:30:55,240 PUBLICATION FROM CANNED WHAT WHO 573 00:30:55,240 --> 00:31:01,360 OBSERVE IN AND REPORTED BI 574 00:31:01,360 --> 00:31:03,120 SEVERAL OTHERS WERE FIRST IN 575 00:31:03,120 --> 00:31:06,760 THIS 1, THE FIBRO MYALGIA 576 00:31:06,760 --> 00:31:08,800 PATIENT HAD DISPLACED MORE FIBRO 577 00:31:08,800 --> 00:31:09,640 NEUROPATHY. 578 00:31:09,640 --> 00:31:13,280 YOU CAN SEE THE SMALL FIBER 579 00:31:13,280 --> 00:31:13,920 NEUROPATHY, RIGHT? 580 00:31:13,920 --> 00:31:21,360 IT'S THE DERMAL AND SUBDERMAL 581 00:31:21,360 --> 00:31:23,400 AND THEY DISAPPEAR AND THEY'RE 582 00:31:23,400 --> 00:31:30,400 SHORT AND NOT FORT RIGHT SHAPE. 583 00:31:30,400 --> 00:31:32,120 IN THE SECOND PUBLICATION WHICH 584 00:31:32,120 --> 00:31:33,920 MAKE YOU THINK ABOUT WHAT NK 585 00:31:33,920 --> 00:31:36,520 CELLS CAN DO, CAME FROM A 586 00:31:36,520 --> 00:31:40,800 PUBLICATION OF ALEX DAVIS IN 587 00:31:40,800 --> 00:31:42,800 CELL 2019 WHEN SHE SHOWED THAT 588 00:31:42,800 --> 00:31:52,360 MAKE SURE KILLER CELLS 589 00:31:52,360 --> 00:31:53,480 REGENERATE SENSORY AFERENT AFTER 590 00:31:53,480 --> 00:31:53,880 NERVE INJURY. 591 00:31:53,880 --> 00:31:56,800 SO BASICALLY HE WAS SAYING IF 592 00:31:56,800 --> 00:31:58,920 THE NERVE WAS DAMAGED, THE NERVE 593 00:31:58,920 --> 00:32:00,880 STARTS TO EXPRESS RECEPTOR FOR 594 00:32:00,880 --> 00:32:02,320 NK CELLS AND IF THEY DON'T 595 00:32:02,320 --> 00:32:05,600 REMOVE IT, IT'S A PROBLEM. 596 00:32:05,600 --> 00:32:09,520 SO WHAT WE DID, WE INCORPORATED 597 00:32:09,520 --> 00:32:11,360 THIS AND TOOK THE SKIN AND WORK 598 00:32:11,360 --> 00:32:14,280 WITH THEM ON THE SKIN BIOPSY OF 599 00:32:14,280 --> 00:32:24,120 FIBRO MYALGIA OF PATIENTS WE 600 00:32:24,120 --> 00:32:26,640 MENTIONED IN STUDIES, THEN WE 601 00:32:26,640 --> 00:32:28,240 SEE EXPRESSION IS MUCH MORE FOR 602 00:32:28,240 --> 00:32:32,120 THE RECEPTOR FOR THE NK CELL, SO 603 00:32:32,120 --> 00:32:33,880 THE NORMAL NERVE NEVER EXPRESS 604 00:32:33,880 --> 00:32:37,200 [INDISCERNIBLE] FOR NK CELLS OR 605 00:32:37,200 --> 00:32:37,840 EXPRESS VERY LOAD. 606 00:32:37,840 --> 00:32:44,360 SO EVERY TIME WHEN THERE IS A NK 607 00:32:44,360 --> 00:33:00,480 CELL RECEPTOR ON, YOU KNOW MAYBE 608 00:33:00,480 --> 00:33:03,640 ANY CELLS--ENRICHMENT FOR THE 609 00:33:03,640 --> 00:33:05,760 NERVE WHICH EXPRESSES IN NK 610 00:33:05,760 --> 00:33:07,760 CELLS BUT ALSO NOT SIGNIFICANT 611 00:33:07,760 --> 00:33:09,320 BUT DEFINITELY INCREASE OR VERY 612 00:33:09,320 --> 00:33:12,680 CLOSE TO THIS INCREASE NUMBER OF 613 00:33:12,680 --> 00:33:14,720 NK CELLS. 614 00:33:14,720 --> 00:33:17,400 AND SO WHAT ALSO WANT IMPORTANT 615 00:33:17,400 --> 00:33:20,600 THAT MOST NUMBER OF NK CELLS 616 00:33:20,600 --> 00:33:23,160 AROUND THE NERVE AND THERE IS 617 00:33:23,160 --> 00:33:29,280 RECEPTOR NK CELLS WAS 618 00:33:29,280 --> 00:33:30,200 SIGNIFICANTLY HIGHLY CORRELATED 619 00:33:30,200 --> 00:33:32,320 AND MOST RECEPTOR FOR NK CELLS 620 00:33:32,320 --> 00:33:35,400 AND NK CELLS THEMSELVES, AROUND 621 00:33:35,400 --> 00:33:39,560 THE NERVE WAS VERY SIGNIFICANTLY 622 00:33:39,560 --> 00:33:41,080 CORRELATED, RISK FIBRO MYALGIA 623 00:33:41,080 --> 00:33:44,400 PAIN SCORE. 624 00:33:44,400 --> 00:33:51,000 SO, OKAY, TOGETHER WOULD WE CAME 625 00:33:51,000 --> 00:33:55,960 WITH THE PROPOSAL FROM THE THIS 626 00:33:55,960 --> 00:33:57,120 HEURISTIC MODEL, WE COULD SEE 627 00:33:57,120 --> 00:34:03,440 WHAT HAPPENED IN FIBRO MYALGIA 628 00:34:03,440 --> 00:34:05,400 IS THE NERVE EXPRESS AREY 629 00:34:05,400 --> 00:34:07,600 RECEPTOR FOR NK CELLS, THEY 630 00:34:07,600 --> 00:34:12,160 CONSTANTLY ATTRACT NK CELLS, AND 631 00:34:12,160 --> 00:34:13,920 NK CELLS OVERTIME BECOME 632 00:34:13,920 --> 00:34:16,200 EXHAUSTED, BUT IT'S ALSO LEAD TO 633 00:34:16,200 --> 00:34:21,400 THE DISTRIBUTION OF NK CELLS TO 634 00:34:21,400 --> 00:34:23,800 [INDISCERNIBLE]. 635 00:34:23,800 --> 00:34:25,280 SO IN CONCLUSION 2, CONCLUSION 636 00:34:25,280 --> 00:34:27,200 TO MY SECOND STORY, WHAT WE 637 00:34:27,200 --> 00:34:31,600 LEARN FROM THIS UNBIASED 638 00:34:31,600 --> 00:34:33,200 [INDISCERNIBLE] THERE IS A 639 00:34:33,200 --> 00:34:38,800 REDISTRIBUTION OF NK CELLS FROM 640 00:34:38,800 --> 00:34:41,400 PERIPHERAL BLOOD TO THE INTRA 641 00:34:41,400 --> 00:34:43,400 DERMAL NERVE FIBERS IN FMS 642 00:34:43,400 --> 00:34:46,120 PATIENTS, BUT THESE NK CELL 643 00:34:46,120 --> 00:34:48,200 EXHIBITED ACTIVATED BUT 644 00:34:48,200 --> 00:34:50,200 EXHAUSTED PHENOTYPES AND INTRA 645 00:34:50,200 --> 00:34:52,880 DERMAL NERVE FIBERS IN FMS 646 00:34:52,880 --> 00:34:54,360 PATIENTS EXPRESS RECEPTOR FOR NK 647 00:34:54,360 --> 00:34:54,600 CELLS. 648 00:34:54,600 --> 00:35:00,760 SO THE NEXT BIG QUESTION, I 649 00:35:00,760 --> 00:35:04,000 WOULD SAY IS WHY THE INTRA 650 00:35:04,000 --> 00:35:06,080 DERMAL NERVE FIBERS ATTRACT 651 00:35:06,080 --> 00:35:07,200 PERIPHERAL NK CELLS, WHY ARE 652 00:35:07,200 --> 00:35:09,800 THEY MARKING THEMSELVES TO BE 653 00:35:09,800 --> 00:35:10,080 REMOVED? 654 00:35:10,080 --> 00:35:14,800 AND THIS SEEMS TO BE THE CHRONIC 655 00:35:14,800 --> 00:35:15,040 PROCESS. 656 00:35:15,040 --> 00:35:19,560 SO THIS NOW WILL BE THE END OF 657 00:35:19,560 --> 00:35:20,800 MY SECOND STORY WITH THE 658 00:35:20,800 --> 00:35:27,600 FINDINGS AND I WILL TELL YOU 659 00:35:27,600 --> 00:35:31,880 LAST STORY, LAST UNDERSTANDING 660 00:35:31,880 --> 00:35:33,400 THAT WAS REVEALED ABOUT 661 00:35:33,400 --> 00:35:34,600 PATHOPHYSIOLOGY OF CHRONIC PAIN, 662 00:35:34,600 --> 00:35:39,960 FOR THE ACUTE INFLAMMATORY 663 00:35:39,960 --> 00:35:42,360 RESPONSE VIA NEUTROPHIL 664 00:35:42,360 --> 00:35:43,760 ACTIVATION PROTECTS AGENCY 665 00:35:43,760 --> 00:35:47,120 KRONIFICATION, SO IN ACUTE 666 00:35:47,120 --> 00:35:49,200 INFLAMMATORY RESPONSE, DURING 667 00:35:49,200 --> 00:35:57,000 NUTRIFILL ACTIVATION PROTECTS 668 00:35:57,000 --> 00:35:58,160 AGAINST PAIN CLONIFICATION, AND 669 00:35:58,160 --> 00:36:01,240 I WILL SHOW YOU RESULTS AND I 670 00:36:01,240 --> 00:36:04,160 HOPE YOU WILL EXCITED WITH ME 671 00:36:04,160 --> 00:36:08,560 ABOUT MORE THIS NEW INSIGHTS. 672 00:36:08,560 --> 00:36:14,080 SO THIS PAPER RIGHT NOW IN 673 00:36:14,080 --> 00:36:14,720 SUBMISSION STAGE. 674 00:36:14,720 --> 00:36:22,600 IN THIS STORY, WE STARTED WITH 675 00:36:22,600 --> 00:36:25,120 HUMAN TRAN SCRIPT ORDER OF 676 00:36:25,120 --> 00:36:28,200 MICRONSICS SO THE SAMPLES CAME 677 00:36:28,200 --> 00:36:29,880 FROM ITALY FROM [INDISCERNIBLE] 678 00:36:29,880 --> 00:36:32,360 AND WE HAD PEOPLE WHOSE LOW BACK 679 00:36:32,360 --> 00:36:36,560 PAIN, IT WAS ACUTE PAIN ABOUT 6 680 00:36:36,560 --> 00:36:37,880 WEEKS OF ACUTE [INDISCERNIBLE] 681 00:36:37,880 --> 00:36:39,880 AND WE HAD BLOOD OF THE PATIENTS 682 00:36:39,880 --> 00:36:41,920 AND WE ALSO HAD BLOOD OF THOSE 683 00:36:41,920 --> 00:36:45,680 PATIENTS 3 MONTHS LATER AND SO, 684 00:36:45,680 --> 00:36:47,680 HALF OF THESE PEOPLE RESOLVED 685 00:36:47,680 --> 00:36:50,000 PAIN AFTER 3 MONTHS, AND HALF OF 686 00:36:50,000 --> 00:36:55,160 THEM STILL WAS HAVING PAIN. 687 00:36:55,160 --> 00:36:57,640 SO WE DID NOTICE THE TRAN CRYPT 688 00:36:57,640 --> 00:37:00,000 ORDER OF MICRONSICS IN 4 689 00:37:00,000 --> 00:37:01,720 DIFFERENT WAYS, SO FIRST WHAT WE 690 00:37:01,720 --> 00:37:02,240 ALMOST, ALMOST, ALMOST, 691 00:37:02,240 --> 00:37:04,960 INTERESTING, WHAT IS THE 692 00:37:04,960 --> 00:37:06,120 DIFFERENCE BETWEEN THOSE WHO 693 00:37:06,120 --> 00:37:08,760 HAVE PERSIST PAIN AND THOSE 694 00:37:08,760 --> 00:37:11,240 AREAS OF PAIN INDICATE STAGE, 695 00:37:11,240 --> 00:37:11,440 RIGHT. 696 00:37:11,440 --> 00:37:14,280 SO THEY ALL WOULD LIKE TO MOVE 697 00:37:14,280 --> 00:37:16,520 THE BIOMARKER FOR THIS PAIN, BUT 698 00:37:16,520 --> 00:37:21,600 BY THE WAY, THE FIRST ANSWER IN 699 00:37:21,600 --> 00:37:22,760 THIS STUDY IS NOT 700 00:37:22,760 --> 00:37:28,400 [INDISCERNIBLE] IN MY LAB. 701 00:37:28,400 --> 00:37:31,640 SO HERE'S THE PLOT, UPREGULATED 702 00:37:31,640 --> 00:37:34,000 GENES, DOWN REGULATED GENES AND 703 00:37:34,000 --> 00:37:35,440 EVERYTHING BELOW THE PINK LINE 704 00:37:35,440 --> 00:37:36,640 IS NOT SIGNIFICANT SO WE 705 00:37:36,640 --> 00:37:41,080 ACTUALLY DIDN'T SEE ANY 706 00:37:41,080 --> 00:37:42,280 SIGNIFICANT GENES IN THE STAGE, 707 00:37:42,280 --> 00:37:43,640 THEY WERE ALL ACUTE. 708 00:37:43,640 --> 00:37:46,400 BUT IN 3 MONTHS WE COMPARED 709 00:37:46,400 --> 00:37:49,400 THOSE WITH RESULT PAIN, 710 00:37:49,400 --> 00:37:50,680 [INDISCERNIBLE] GENES WE SAW 711 00:37:50,680 --> 00:37:56,800 ALMOST 2000 GENES UP AND DOWN 712 00:37:56,800 --> 00:37:58,320 REGULATED, DIFFERENT BETWEEN 713 00:37:58,320 --> 00:37:59,600 PEOPLE [INDISCERNIBLE] OF PAIN 714 00:37:59,600 --> 00:38:11,400 AND [INDISCERNIBLE] OF PAIN. 715 00:38:11,400 --> 00:38:13,000 UPON FOR PEOPLE IN THEM, FOR 716 00:38:13,000 --> 00:38:14,920 THOSE RESULTS. 717 00:38:14,920 --> 00:38:17,280 AND THIS IS WHAT EXPLOSION IS 718 00:38:17,280 --> 00:38:19,880 REALLY HAPPENED IS WHEN YOU LOOK 719 00:38:19,880 --> 00:38:21,760 AT THE PEOPLE WHO OBSERVE PAIN 720 00:38:21,760 --> 00:38:22,400 OVER TIME, YOU SLEEP APNEA AND 721 00:38:22,400 --> 00:38:27,280 OBESITYY THERE'S HALF OF THE 722 00:38:27,280 --> 00:38:32,080 GENOME DIFFERENTIALLY EXPRESSED 723 00:38:32,080 --> 00:38:33,560 AT GENOME WIDE [INDISCERNIBLE] 724 00:38:33,560 --> 00:38:35,360 SO IT'S LIKE UNBELIEVABLE 725 00:38:35,360 --> 00:38:39,120 RESPONSE, IN THOSE WHO RESOLVE 726 00:38:39,120 --> 00:38:39,320 PAIN. 727 00:38:39,320 --> 00:38:41,880 IN THOSE WHO DON'T RESOLVE PAIN, 728 00:38:41,880 --> 00:38:42,880 WHAT HAS HAPPENED? 729 00:38:42,880 --> 00:38:50,840 ABSOLUTELY NOTHING. 730 00:38:50,840 --> 00:38:57,200 IT ABSOLUTELY COLLAPSE 731 00:38:57,200 --> 00:38:57,920 TRANSCRIPTION RESPONSE. 732 00:38:57,920 --> 00:39:01,560 SO WE ALSO RECONSTRUCT FROM 733 00:39:01,560 --> 00:39:02,480 TRANSCRIPT OMICS FROM THE 734 00:39:02,480 --> 00:39:05,200 DIFFERENT CELLS AND WHERE WE SAW 735 00:39:05,200 --> 00:39:08,240 THE DIFFERENCE IS AGAIN WHEN WE 736 00:39:08,240 --> 00:39:09,520 FOLLOW THE RESOLVERS OVERTIME, 737 00:39:09,520 --> 00:39:13,200 IN THIS CASE, WE THE MOST 738 00:39:13,200 --> 00:39:15,680 SOLUTION IS THE DOWN REGULATION 739 00:39:15,680 --> 00:39:18,840 OF NUTRIFILLS OVER TIME AND DOWN 740 00:39:18,840 --> 00:39:21,240 REGULATION OF MASS CELLS 741 00:39:21,240 --> 00:39:23,240 OVERTIME BUT UPREGULATION OF 742 00:39:23,240 --> 00:39:25,680 T-CELLS AND UPREGULATION OF NK 743 00:39:25,680 --> 00:39:34,480 CELLS OVER TIME AND THOSE WERE 744 00:39:34,480 --> 00:39:34,840 THE RESULTS. 745 00:39:34,840 --> 00:39:36,880 SOY NEXT WE ASK THE QUESTION, 746 00:39:36,880 --> 00:39:39,840 OKAY, WELL, STILL SOMETHING MUST 747 00:39:39,840 --> 00:39:41,520 HAPPEN AT ACUTE STAGE THAT LEADS 748 00:39:41,520 --> 00:39:48,600 TO ALL THIS MASSIVE 749 00:39:48,600 --> 00:39:49,600 TRANSCRIPTION CHANGES IN THESE 750 00:39:49,600 --> 00:39:50,960 STUDIES SO MAYBE WE CAN USE 751 00:39:50,960 --> 00:39:52,840 OTHER TOOLS WHICH WILL BE MORE 752 00:39:52,840 --> 00:39:53,520 STATISTICALLY POWERFUL AND WHAT 753 00:39:53,520 --> 00:39:56,360 WE DID WAS THE PATHWAY ANALYSIS. 754 00:39:56,360 --> 00:39:59,160 SO WHEN WE DID PATHWAY ANALYSIS, 755 00:39:59,160 --> 00:40:02,720 MANY, MANY PATHWAY WAS 756 00:40:02,720 --> 00:40:05,560 SIGNIFICANT AT TIME 0 757 00:40:05,560 --> 00:40:08,720 [INDISCERNIBLE], BUT THE 2 758 00:40:08,720 --> 00:40:12,160 [INDISCERNIBLE] WAS INFLAMMATORY 759 00:40:12,160 --> 00:40:12,840 RESPONSE. 760 00:40:12,840 --> 00:40:17,000 NEARER FROM THE RESPONSE FOR THE 761 00:40:17,000 --> 00:40:19,960 ACUTE INFLAMMATORY RESPONSE. 762 00:40:19,960 --> 00:40:21,280 THE SURPRISE THOSE WHO RESOLVED 763 00:40:21,280 --> 00:40:25,480 PAIN HAVE MUCH HIGHER 764 00:40:25,480 --> 00:40:27,240 INFLAMMATORY RESPONSE, WHICH IN 765 00:40:27,240 --> 00:40:29,680 THIS INFLAMMATORY RESPONSE WAS 766 00:40:29,680 --> 00:40:31,200 SIGNIFICANTLY DOWN REGULATED 767 00:40:31,200 --> 00:40:34,160 OVER TIME SO THEY HAVE IT VERY 768 00:40:34,160 --> 00:40:36,920 HIGH FOR THIS STAGE DOWN 769 00:40:36,920 --> 00:40:37,200 REGULATED. 770 00:40:37,200 --> 00:40:43,280 SO, IT'S--IT'S ALSO KIND OF 771 00:40:43,280 --> 00:40:46,120 CONSISTENT WHICH WAS 772 00:40:46,120 --> 00:40:46,680 DIFFERENTIATED FOR 773 00:40:46,680 --> 00:40:48,200 [INDISCERNIBLE] AND 774 00:40:48,200 --> 00:40:48,880 NON[INDISCERNIBLE], AND 775 00:40:48,880 --> 00:40:50,160 LEUCOCYTE ACTIVATION, AND FROM 776 00:40:50,160 --> 00:40:52,440 LEUCOCYTE ACTIVATION IT WAS 777 00:40:52,440 --> 00:40:53,800 NUTRIFILL WHICH WAS 778 00:40:53,800 --> 00:40:54,920 SIGNIFICANTLY MORE DIFFERENT. 779 00:40:54,920 --> 00:40:58,200 SO IT WAS NUTRIFILL ACTIVATION 780 00:40:58,200 --> 00:40:59,440 AND NUTRIFILL GRANULATION WHICH 781 00:40:59,440 --> 00:41:01,880 WAS MUCH HIGHER AGAIN IN PEOPLE 782 00:41:01,880 --> 00:41:03,960 WHO VIEWED THIS PAIN, IN THIS 783 00:41:03,960 --> 00:41:06,600 RESPONSE WAS DONE REGULATED AND 784 00:41:06,600 --> 00:41:11,800 THE RESULT WAS VERY SIGNIFICANT 785 00:41:11,800 --> 00:41:16,560 OVER 3 MONTHS. 786 00:41:16,560 --> 00:41:22,600 AND SO, ALSO WE LOOK AT OVERALL 787 00:41:22,600 --> 00:41:23,920 RESPONSE ESPECIALLY BECAUSE I 788 00:41:23,920 --> 00:41:28,960 COULDN'T FIRST UNDERSTAND THE 789 00:41:28,960 --> 00:41:29,960 DIFFERENCE BETWEEN--SO HOW COME 790 00:41:29,960 --> 00:41:35,000 WE HAVE ONLY LIKE 2000 GENE 791 00:41:35,000 --> 00:41:35,840 BETWEEN [INDISCERNIBLE] AND 792 00:41:35,840 --> 00:41:38,640 RESOLVERS IN 3 MONTHS BUT SUCH 793 00:41:38,640 --> 00:41:39,800 EXPLOSION ON DIFFERENTIAL 794 00:41:39,800 --> 00:41:41,000 EXPRESSION IN PEOPLE WHO RESOLVE 795 00:41:41,000 --> 00:41:43,640 PAIN AND THE ANSWER IS, WELL, 796 00:41:43,640 --> 00:41:47,520 THE MOST RESOLVED PAIN AND 797 00:41:47,520 --> 00:41:49,680 UNRESOLVED PAIN, THE TRANSCRIPT 798 00:41:49,680 --> 00:41:51,280 OMICS CORRELATE OVER TIME, SO 799 00:41:51,280 --> 00:41:56,360 HERE'S THE GOLDEN LINE, IT'S THE 800 00:41:56,360 --> 00:41:56,880 PERFECT CORRELATION. 801 00:41:56,880 --> 00:42:01,000 BUT YOU SEE WE HAVE THIS MA 802 00:42:01,000 --> 00:42:03,840 JEBTA LINE, VERY SIGNIFICANT, 803 00:42:03,840 --> 00:42:06,600 YEAH, BUT THIS DIFFERENCE 804 00:42:06,600 --> 00:42:08,160 PROVIDE US 30% DIFFERENCE, SO 805 00:42:08,160 --> 00:42:10,200 THOSE WHO DON'T RESOLVE PAIN 806 00:42:10,200 --> 00:42:13,200 THEY KIND OF TRIED TO MOVE THE 807 00:42:13,200 --> 00:42:15,240 SAME THINGS, THEY TRIED TO 808 00:42:15,240 --> 00:42:19,120 UPREGULATE THE SAME PATHWAY, BUT 809 00:42:19,120 --> 00:42:28,240 THIS RESPONSE IS VERY, 810 00:42:28,240 --> 00:42:29,440 VERY--VERY BLUNTED, YOU KNOW 811 00:42:29,440 --> 00:42:29,800 [INDISCERNIBLE]. 812 00:42:29,800 --> 00:42:31,440 SO FINALLY THIS IS WHAT WAS 813 00:42:31,440 --> 00:42:36,000 SUGGESTED ON THE HUMAN STUDY, 814 00:42:36,000 --> 00:42:40,400 WHAT'S HAPPENING, AT ACUTE STAGE 815 00:42:40,400 --> 00:42:42,920 WE HAVE HIGH INFLUENCER RESPONSE 816 00:42:42,920 --> 00:42:46,400 IN HIS AREAS, BUT THIS 817 00:42:46,400 --> 00:42:47,400 INFLAMMATORY RESPONSE GOES DOWN, 818 00:42:47,400 --> 00:42:49,600 BUT WHAT I DIDN'T HAVE TIME TO 819 00:42:49,600 --> 00:42:52,000 FOCUS, THE REPLICATE THIS 820 00:42:52,000 --> 00:42:55,400 RESOLVE, IN 2 OTHER COHORT SO 1 821 00:42:55,400 --> 00:42:58,880 OF THEM WAS IN [INDISCERNIBLE], 822 00:42:58,880 --> 00:43:01,200 IT'S A FACIAL PAIN, ALSO WE HAD 823 00:43:01,200 --> 00:43:03,120 ACUTE ASK CHRONIC AND OTHER 824 00:43:03,120 --> 00:43:05,400 SYSTEM AND IT WAS THE SAME. 825 00:43:05,400 --> 00:43:07,560 SO INFLAMMATORY RESPONSE IS HIGH 826 00:43:07,560 --> 00:43:23,720 IN THOSE AREAS OF PAIN--ACUTE 827 00:43:23,720 --> 00:43:25,400 STAGE, THERE IT IS WORSE EVEN, 828 00:43:25,400 --> 00:43:26,800 YOU KNOW CONTINUE TO GO UP AND 829 00:43:26,800 --> 00:43:29,240 UP AND UP AND UP AND THIS IS 830 00:43:29,240 --> 00:43:30,640 WHAT WOULD EXPLAIN, THIS WOULD 831 00:43:30,640 --> 00:43:32,840 EXPLAIN WHAT WE SEE THAT IN 832 00:43:32,840 --> 00:43:35,480 CHRONIC PAIN PATIENT, THERE IS 833 00:43:35,480 --> 00:43:37,600 MORE GREAT INFLAMMATION, IT IS 834 00:43:37,600 --> 00:43:39,640 MORE GREAT INFLAMMATION IN 835 00:43:39,640 --> 00:43:41,880 PERSISTENT PATIENTS BECAUSE, 836 00:43:41,880 --> 00:43:44,840 YEAH, THEY DIDN'T DO THE CORRECT 837 00:43:44,840 --> 00:43:46,160 UPREGULATION AND DOWN REGULATION 838 00:43:46,160 --> 00:43:48,680 YOU KNOW IN THE ACUTE STAGE. 839 00:43:48,680 --> 00:43:53,400 AND SO ALSO FROM OTHER CORPORATE 840 00:43:53,400 --> 00:43:55,280 CONSTRUCT WHAT HAPPENED, BEFORE 841 00:43:55,280 --> 00:44:01,560 EVEN IF ACUTE STAGE IN THE BASE 842 00:44:01,560 --> 00:44:06,280 LINE IS PEOPLE WHO WILL HAVE THE 843 00:44:06,280 --> 00:44:08,200 HIGH INHIBITORY RESPONSE, ALSO 844 00:44:08,200 --> 00:44:10,800 THEY INCLUDE THE INHIBITORY 845 00:44:10,800 --> 00:44:13,600 RESPONSE BEFORE THEY RESOLVE. 846 00:44:13,600 --> 00:44:15,560 IN THOSE WHO HAVE NO RESPONSE, 847 00:44:15,560 --> 00:44:18,320 THEY WERE ALREADY HIGH. 848 00:44:18,320 --> 00:44:23,400 SO IT'S THIS [INDISCERNIBLE] 849 00:44:23,400 --> 00:44:25,720 RESPONSE INTO THIS 850 00:44:25,720 --> 00:44:26,840 [INDISCERNIBLE] Q-RESPONSE, SO 851 00:44:26,840 --> 00:44:28,200 THEN WE STARTED ANIMAL STUDIES 852 00:44:28,200 --> 00:44:31,600 AND WE STUDIED THIS IN THE LAB 853 00:44:31,600 --> 00:44:33,560 OF JEFF [INDISCERNIBLE] IN HIS 854 00:44:33,560 --> 00:44:35,800 POST DOC LUCAS AND SO JEFF 855 00:44:35,800 --> 00:44:38,040 ORIGINALLY HE SAID, YOU KNOW IT 856 00:44:38,040 --> 00:44:40,800 CANNOT BE BECAUSE WHAT YOU'RE 857 00:44:40,800 --> 00:44:44,080 SAYING THAT THE INFLAMMATION IS 858 00:44:44,080 --> 00:44:47,560 GOOD BUT WE ALL KNOW THAT 859 00:44:47,560 --> 00:44:49,480 INFLAMMATORY DRUG INDUCE PAIN. 860 00:44:49,480 --> 00:44:51,360 AND THEN WE TALK MORE AND HE 861 00:44:51,360 --> 00:44:52,760 SAID, WELL, PEOPLE PROBABLY 862 00:44:52,760 --> 00:44:57,040 NEVER LOOK OVER TIME, SO LET'S 863 00:44:57,040 --> 00:45:00,360 SEE WHAT'S HAPPENED OVER TIME. 864 00:45:00,360 --> 00:45:03,360 SO JEFF AND LUCAS CAME IN AND 865 00:45:03,360 --> 00:45:06,200 THEY TOOK MICE, THEY DID SEVERAL 866 00:45:06,200 --> 00:45:08,840 ANIMAL PAIN MODEL BUT HERE WE'RE 867 00:45:08,840 --> 00:45:14,440 TALKING PRESENT IT'S A C-FRAME 868 00:45:14,440 --> 00:45:15,080 INFLAMMATORY--CFA INFLAMMATORY 869 00:45:15,080 --> 00:45:19,000 MODEL SO WE SEE THE MICE AND 870 00:45:19,000 --> 00:45:21,400 THEY INJECT TO MICE DEXAMETHA 871 00:45:21,400 --> 00:45:26,800 SEWN FOR A FEW DAYS, FOR 3 DAYS, 872 00:45:26,800 --> 00:45:29,200 ASK THEN THEY WAY AND THEN LOOK 873 00:45:29,200 --> 00:45:34,720 AT PAIN BEHAVIOR OF THE MICE. 874 00:45:34,720 --> 00:45:36,600 AND YOU SEE THIS MOVE IS 875 00:45:36,600 --> 00:45:39,160 HAPPENING AT ACUTE STAGE AND AT 876 00:45:39,160 --> 00:45:43,000 ACUTE STAGE MICE THAT RECEIVED 877 00:45:43,000 --> 00:45:44,440 DEXAMETHASONE, IT'S HIGH AND THE 878 00:45:44,440 --> 00:45:49,000 WORK IS ALAN GEEZIC AND MICE WHO 879 00:45:49,000 --> 00:45:51,120 RECEIVE SALIVA--SALIVAINE, THEY 880 00:45:51,120 --> 00:45:53,400 WILL HAVE ANALGESIC, BUT IF YOU 881 00:45:53,400 --> 00:45:57,680 FOLLOW THEM OVER TIME, IT'S A 882 00:45:57,680 --> 00:46:02,800 CLOSE SWITCH BECAUSE AT DAY 15, 883 00:46:02,800 --> 00:46:04,720 THE MICE WAS [INDISCERNIBLE] 884 00:46:04,720 --> 00:46:10,960 ALREADY BUT MICE WHO RECEIVE THE 885 00:46:10,960 --> 00:46:12,680 DEXAMETHASONE, THEY BECAME HYPER 886 00:46:12,680 --> 00:46:14,000 ANALGESIC AND THESE NUMBERS ARE 887 00:46:14,000 --> 00:46:15,680 VERY SIMILAR WHEN IT WAS 888 00:46:15,680 --> 00:46:19,040 RESOLVED VERY QUICKLY, SO YOU 889 00:46:19,040 --> 00:46:27,240 SEE THIS MAY CERTIFY MICE WHO 890 00:46:27,240 --> 00:46:29,400 RECEIVED DEXAMETHASONE, IT TOOK 891 00:46:29,400 --> 00:46:33,320 THEM 140 DAYS, I MEAN IT'S LIKE 892 00:46:33,320 --> 00:46:38,720 A HALF--HALF LIFE JUST FOR 2 893 00:46:38,720 --> 00:46:41,040 SHORT OF DEXAMETHA SEWN AT A 894 00:46:41,040 --> 00:46:45,480 VERY ACUTE STAGE. 895 00:46:45,480 --> 00:46:53,200 AND WE THEN CHECK OTHER DOCS, 896 00:46:53,200 --> 00:47:00,440 AND WE CHECK ON GABBAPENTINE 897 00:47:00,440 --> 00:47:01,560 REGIMENIN AND LIDOCAINE AND 898 00:47:01,560 --> 00:47:02,600 [INDISCERNIBLE], AND DOING THE 899 00:47:02,600 --> 00:47:05,480 SAME THING, SO FIRST OF ALL, 900 00:47:05,480 --> 00:47:07,240 USUALLY ALL THIS ANALGESIC 901 00:47:07,240 --> 00:47:10,000 DRUGS, THEY ARE ANALGESIC SO AT 902 00:47:10,000 --> 00:47:12,000 ACUTE STAGE, THEY ARE ANALGESIC, 903 00:47:12,000 --> 00:47:14,880 THEY HAVE MICE BUT WHAT'S 904 00:47:14,880 --> 00:47:17,680 HAPPENED THIS MICE WHO RECEIVED 905 00:47:17,680 --> 00:47:18,840 THE [INDISCERNIBLE], THEY 906 00:47:18,840 --> 00:47:20,720 DEVELOP THEIR OWN HYPER 907 00:47:20,720 --> 00:47:25,680 ANALGESIC STAYS FOR A VERY, VERY 908 00:47:25,680 --> 00:47:29,600 LONG TIME. 909 00:47:29,600 --> 00:47:34,640 SO FINALLY, WE DECIDED TO CHECK, 910 00:47:34,640 --> 00:47:36,600 YOU KNOW NUTRIFILL, REMEMBER IN 911 00:47:36,600 --> 00:47:38,480 HUMANS IT WAS PATHWAY ANALYSIS 912 00:47:38,480 --> 00:47:41,520 IN THE CELL COMPOSITION, IT WAS 913 00:47:41,520 --> 00:47:44,200 SUGGEST THAD ROOTS NEUTROPHIL 914 00:47:44,200 --> 00:47:46,400 THAT IS CRITICAL FOR THE 915 00:47:46,400 --> 00:47:48,280 CONTRIBUTORS TO PAIN 916 00:47:48,280 --> 00:47:55,280 KRONIFICATION OF PAIN, SO THEN 917 00:47:55,280 --> 00:48:00,080 WE REMOVE THIS ANTIBODY WHICH 918 00:48:00,080 --> 00:48:00,840 REMOVE NEUTROPHIL WHICH IS 919 00:48:00,840 --> 00:48:05,400 EXACTLY THE SAME PICTURE AS 920 00:48:05,400 --> 00:48:08,000 USING DEXAMETHASONE, SO IT'S 921 00:48:08,000 --> 00:48:10,560 CREATE THIS, MAYBE A LITTLE BIT 922 00:48:10,560 --> 00:48:12,200 ANALGESIC PHENOTYPE IN THE 923 00:48:12,200 --> 00:48:29,560 BEGINNING BUT LONG, LONG, LONG 924 00:48:29,560 --> 00:48:31,280 HYPER [INDISCERNIBLE]. 925 00:48:31,280 --> 00:48:36,200 TO OUR DEXAMETHA SEWN STUDY, SO, 926 00:48:36,200 --> 00:48:39,320 THE DEXAMETHA SEWN YOU SEE THE 927 00:48:39,320 --> 00:48:42,400 DEXAMETHA SEWN, AND THEY DEVELOP 928 00:48:42,400 --> 00:48:46,720 LONG TIME HYPER ALGEESIA, BUT IF 929 00:48:46,720 --> 00:48:51,680 YOU GIVE MICE IN THE NEUTROPHILS 930 00:48:51,680 --> 00:48:57,440 OR, SO PROTEIN WHICH IS ACE 931 00:48:57,440 --> 00:49:00,280 HUNDRED 8 OR 9 WHICH IS THE 932 00:49:00,280 --> 00:49:03,000 SIGNALING THAT MANY RECEIVE IN 933 00:49:03,000 --> 00:49:06,200 MOLECULES OF NEUTROPHILS, YOU 934 00:49:06,200 --> 00:49:11,400 COMPLETELY ELIMINATE THIS HYPER 935 00:49:11,400 --> 00:49:11,760 ALGEESIA. 936 00:49:11,760 --> 00:49:14,560 SO FINALLY FOR THIS STORY FROM 937 00:49:14,560 --> 00:49:16,400 MY FAVORITE UK BIOBANK IS 938 00:49:16,400 --> 00:49:23,800 REMEMBER IN UK BIOBANK, WE HAD 939 00:49:23,800 --> 00:49:25,800 THIS PAIN SITE BUT WE ALSO HAVE 940 00:49:25,800 --> 00:49:27,080 LIKE AMARKER OF ACUTE PAIN 941 00:49:27,080 --> 00:49:27,960 BECAUSE THE FIRST QUESTION YOU 942 00:49:27,960 --> 00:49:30,520 REMEMBER WAS IN THE LAST MONTHS, 943 00:49:30,520 --> 00:49:32,800 HAVE YOU EXPERIENCED ANY OF THE 944 00:49:32,800 --> 00:49:34,760 FOLLOWING PAIN WHICH INTERFERED 945 00:49:34,760 --> 00:49:36,600 WITH YOUR USUAL ACTIVITY. 946 00:49:36,600 --> 00:49:38,760 SO, PEOPLE CAN SAY, YES IN THE 947 00:49:38,760 --> 00:49:41,400 LAST MONTH BUT SAY NO IT HASN'T 948 00:49:41,400 --> 00:49:44,680 BEEN FOR 3 MONTHS. 949 00:49:44,680 --> 00:49:48,320 SO WHAT WE DID, WE LOOK AT THE 950 00:49:48,320 --> 00:49:50,240 BASE LINE FOR ACUTE PAIN FOR 951 00:49:50,240 --> 00:49:52,240 BIOBANK, PEOPLE SAY YES, I HAVE 952 00:49:52,240 --> 00:49:55,800 PAIN BUT NO, IT'S NOT 3 MONTHS 953 00:49:55,800 --> 00:49:57,960 AND THEN WE SO MOVE THEM, WE 954 00:49:57,960 --> 00:49:59,360 HAVE DRUG USAGE FOR THESE 955 00:49:59,360 --> 00:50:02,080 PEOPLE, ALL OF THEM DEVELOP 956 00:50:02,080 --> 00:50:05,200 CHRONIC PAIN AT THE SECOND VISIT 957 00:50:05,200 --> 00:50:07,760 WHICH WAS 2-6 YEARS LECTURE. 958 00:50:07,760 --> 00:50:10,240 AND AGAIN, SURPRISE, SURPRISE, 959 00:50:10,240 --> 00:50:12,200 LOOK AT THE ALL DRUG AVAILABLE, 960 00:50:12,200 --> 00:50:16,400 YOU LOOK AT ALL DRUGS AVAILABLE 961 00:50:16,400 --> 00:50:18,440 WHEN AT LEAST 10 PEOPLE THAT 962 00:50:18,440 --> 00:50:20,000 WOULD TAKE A DRUG AT THAT STAGE 963 00:50:20,000 --> 00:50:24,000 AND SO HERE WE END UP HAVING 964 00:50:24,000 --> 00:50:27,720 NSAID AND ANTI[INDISCERNIBLE], 965 00:50:27,720 --> 00:50:29,400 AND YOU SEE ONLY SIGNIFICANT IN 966 00:50:29,400 --> 00:50:31,800 A DIFFERENT MODEL IN THE WAY 967 00:50:31,800 --> 00:50:34,200 THAT PEOPLE WHO TAKE NSAIDS WHEN 968 00:50:34,200 --> 00:50:37,960 THEY HAD ACUTE EPISODE, THEY 969 00:50:37,960 --> 00:50:43,160 WERE 1.7 TIMES MORE LIKELY TO 970 00:50:43,160 --> 00:50:44,480 DEVELOP CHRONIC--TO HAVE CHRONIC 971 00:50:44,480 --> 00:50:52,520 PAIN AT THE SECOND VISIT. 972 00:50:52,520 --> 00:51:08,560 INCLUDING CORRECTION FOR ALL 973 00:51:08,560 --> 00:51:08,760 DRUGS. 974 00:51:08,760 --> 00:51:11,000 YES THERE IS AN ADAPTIVE 975 00:51:11,000 --> 00:51:12,920 COMPONENT IN THE IMMUNE SYSTEM, 976 00:51:12,920 --> 00:51:15,200 IN ACUTE GROWING TRANSITION IN 977 00:51:15,200 --> 00:51:19,080 THE LIKE THE OTHER CHRONIC PAIN 978 00:51:19,080 --> 00:51:20,280 CONDITION. 979 00:51:20,280 --> 00:51:24,840 AND SO THERE'S IMMEDIATE ACTIVE 980 00:51:24,840 --> 00:51:26,520 IMMUNE RESPONSE IN HUMAN, THIS 981 00:51:26,520 --> 00:51:34,200 PHYSICAL INJURY MAY LEAD TO PAIN 982 00:51:34,200 --> 00:51:36,120 CHRONIFICATION. 983 00:51:36,120 --> 00:51:41,560 SO THE CONCLUSION OF THIS THEN, 984 00:51:41,560 --> 00:51:43,560 THERE'S DESPITE HIGHER EFFICACY 985 00:51:43,560 --> 00:51:44,360 AT EARLY TIME POINT THE INHIB 986 00:51:44,360 --> 00:51:47,520 THORS INCREASE IN BODYITION OF 987 00:51:47,520 --> 00:51:48,360 ACUTE INFLAMMATORY RESPONSE 988 00:51:48,360 --> 00:51:49,840 MANAGEMENT MAY BE COUNTER 989 00:51:49,840 --> 00:51:52,720 PRODUCTIVE FOR LONG-TERM OF 990 00:51:52,720 --> 00:51:56,600 OUTCOME OF [INDISCERNIBLE] PAIN 991 00:51:56,600 --> 00:51:57,600 SUFFERS. 992 00:51:57,600 --> 00:52:03,640 SO WITH THIS, I WANT TO THANK 993 00:52:03,640 --> 00:52:04,840 YOU VERY MUCH FOR YOUR 994 00:52:04,840 --> 00:52:05,120 ATTENTION. 995 00:52:05,120 --> 00:52:07,440 I WANT TO SAY THANK TO YOU OUR 996 00:52:07,440 --> 00:52:09,360 GROWING PAIN GENETICS GROUP 997 00:52:09,360 --> 00:52:14,160 WHICH IS A BIG GROUP OF 998 00:52:14,160 --> 00:52:15,200 [INDISCERNIBLE] STUDENTS AND I 999 00:52:15,200 --> 00:52:17,800 WANT TO SAY THANK YOU FOR ALL 1000 00:52:17,800 --> 00:52:20,240 FUNDING AGENCY UPON STARTING AT 1001 00:52:20,240 --> 00:52:21,480 NIH, AND OF COURSE Mc GILL 1002 00:52:21,480 --> 00:52:22,480 UNIVERSITY TO DO ALL THE 1003 00:52:22,480 --> 00:52:23,120 RESEARCH. 1004 00:52:23,120 --> 00:52:24,920 THANK YOU VERY MUCH. 1005 00:52:24,920 --> 00:52:26,440 >> I AM A SCIENTISTS FOR 1006 00:52:26,440 --> 00:52:30,520 NATIONAL CENTER FOR 1007 00:52:30,520 --> 00:52:32,360 BIOTECHNOLOGY AND INFORMATION, 1008 00:52:32,360 --> 00:52:35,880 FROM NCBI AND I AM 1009 00:52:35,880 --> 00:52:38,240 INVOLVED IN THE ACUTE 1010 00:52:38,240 --> 00:52:38,840 [INDISCERNIBLE] SESSION TODAY, 1011 00:52:38,840 --> 00:52:41,040 THANK YOU VERY MUCH DOCTOR FOR 1012 00:52:41,040 --> 00:52:41,680 YOUR WONDERFUL TALK. 1013 00:52:41,680 --> 00:52:45,560 YOU HAVE SEVERAL QUESTIONS FOR 1014 00:52:45,560 --> 00:52:50,000 YOU AND WE DON'T HAVE TIME FOR 1015 00:52:50,000 --> 00:52:52,200 ALL THESE QUESTIONS AND FIRST OF 1016 00:52:52,200 --> 00:52:55,960 ALL IT WAS TO CONTINUE MEDICAL 1017 00:52:55,960 --> 00:52:57,840 EDUCATION, THEY SEE 1018 00:52:57,840 --> 00:53:05,240 [INDISCERNIBLE] FOR IT IS 37933. 1019 00:53:05,240 --> 00:53:21,720 I WILL REPEAT IT. 1020 00:53:21,720 --> 00:53:23,600 37933. 1021 00:53:23,600 --> 00:53:26,080 I WILL USE MY [INDISCERNIBLE] TO 1022 00:53:26,080 --> 00:53:32,120 USE FOR Q&A SESSION AND I WILL 1023 00:53:32,120 --> 00:53:33,320 ASK FIRST, DOCTOR, DURING YOUR 1024 00:53:33,320 --> 00:53:35,520 TALK YOU STATED A POTENTIALLY 1025 00:53:35,520 --> 00:53:39,840 LONG EFFECT TO FIND INFLAMMATORY 1026 00:53:39,840 --> 00:53:41,040 DRUGS FOR DIFFERENT PAIN 1027 00:53:41,040 --> 00:53:42,560 CONDITIONS AND WHAT WOULD YOU 1028 00:53:42,560 --> 00:53:44,120 SUGGEST TO USE? 1029 00:53:44,120 --> 00:53:45,400 WE ARE HAVING THOUGHTS ABOUT 1030 00:53:45,400 --> 00:53:50,720 DEVELOPING A NEW THERAPY FOR 1031 00:53:50,720 --> 00:53:54,440 CHRONIC PAIN. 1032 00:53:54,440 --> 00:53:57,680 >> YES, WE SPEND A LOT OF TIME 1033 00:53:57,680 --> 00:54:00,280 THINKING IF WE CAN'T USE NSAID, 1034 00:54:00,280 --> 00:54:02,960 WHAT CAN WE USE? 1035 00:54:02,960 --> 00:54:05,840 AND I THINK WHAT IS IMPORTANT IF 1036 00:54:05,840 --> 00:54:13,480 WE THINK ABOUT OUR RESULTS IS 1037 00:54:13,480 --> 00:54:16,200 THAT--THE UNUSUAL OR UNEXPECTED 1038 00:54:16,200 --> 00:54:23,600 KIND OF ANGLES OF OUR DISCOVERY 1039 00:54:23,600 --> 00:54:25,120 IS THAT IT'S NOT WHAT WE USUALLY 1040 00:54:25,120 --> 00:54:28,000 THINK ABOUT THAT IT'S NOT 1 1041 00:54:28,000 --> 00:54:33,160 MOLECULE AND IT'S NOT LINEAR 1042 00:54:33,160 --> 00:54:33,400 RESPONSE. 1043 00:54:33,400 --> 00:54:34,680 SO WE OFTEN THINK ABOUT PROCESS 1044 00:54:34,680 --> 00:54:38,000 AND THE PAIN PROCESS THAT THERE 1045 00:54:38,000 --> 00:54:40,840 IS 1 GENE SHOULD CONTINUE AND 1046 00:54:40,840 --> 00:54:45,040 THE FURTHER IT GOES, THE MORE 1047 00:54:45,040 --> 00:54:46,160 YEAH IT CONTINUES TO THE 1048 00:54:46,160 --> 00:54:52,520 PROCESS, BUT WHAT WE SAW FROM 1049 00:54:52,520 --> 00:54:55,200 OUR DATA, NO, UPON IT'S 1050 00:54:55,200 --> 00:54:57,280 [INDISCERNIBLE] AND IT'S ALSO 1051 00:54:57,280 --> 00:54:59,440 HUGE ACTIVITY WHICH IS 1052 00:54:59,440 --> 00:55:03,920 ASSOCIATED WITH THE PROCESS OF 1053 00:55:03,920 --> 00:55:04,760 CAN [INDISCERNIBLE], OKAY? 1054 00:55:04,760 --> 00:55:09,400 SO ANOTHER THOUGHT PROCESS IS 1055 00:55:09,400 --> 00:55:11,200 THAT WE ONLY STUDY PEOPLE WHO 1056 00:55:11,200 --> 00:55:12,600 DEVELOP CHRONIC PAIN. 1057 00:55:12,600 --> 00:55:16,640 BUT, IF YOU REMEMBER, MY, YOU 1058 00:55:16,640 --> 00:55:27,560 KNOW VERY FIRST SLIDE, REALLY 1059 00:55:27,560 --> 00:55:28,640 THOSE WHO RESOLVE PAIN, THIS IS 1060 00:55:28,640 --> 00:55:32,000 WHERE THE ACTION IS. 1061 00:55:32,000 --> 00:55:34,440 THOSE WHO DON'T RESOLVE PAIN, 1062 00:55:34,440 --> 00:55:34,800 NOTHING HAPPEN. 1063 00:55:34,800 --> 00:55:37,760 IT IS VERY DIFFICULT TO FIND 1064 00:55:37,760 --> 00:55:39,200 BLACK CAT IN BLACK ROOM, RIGHT? 1065 00:55:39,200 --> 00:55:40,160 IT'S VERY DIFFICULT TO 1066 00:55:40,160 --> 00:55:43,560 UNDERSTAND WHAT DIDN'T HAPPEN TO 1067 00:55:43,560 --> 00:55:43,920 THESE PEOPLE. 1068 00:55:43,920 --> 00:55:47,120 SO FIRST OF ALL WE NEED TO STUDY 1069 00:55:47,120 --> 00:55:48,320 WHAT'S HAPPENED IN PEOPLE WHEN 1070 00:55:48,320 --> 00:55:50,560 ON RESOLVE PAIN AND SECOND, YOU 1071 00:55:50,560 --> 00:55:53,960 KNOW IN ACCORDANCE WITH THIS 1072 00:55:53,960 --> 00:55:56,720 DATA, I UPON SAW THAT THEN MAYBE 1073 00:55:56,720 --> 00:56:01,040 SHOULD WORK IS THE THERAPY WHICH 1074 00:56:01,040 --> 00:56:03,480 WOULD INHIBIT SOME PROCESSES, 1075 00:56:03,480 --> 00:56:07,840 BUT UPREGULATE SOME PROCESSES, 1076 00:56:07,840 --> 00:56:08,920 UPREGULATE OUR IMMUNE RESPONSE. 1077 00:56:08,920 --> 00:56:12,000 AND THEN WHAT WE KNOW, LOOKING 1078 00:56:12,000 --> 00:56:14,440 FOR PAIN, WELL WE KNOW PHYSICAL 1079 00:56:14,440 --> 00:56:24,800 THERAPY IS WORKING, EXERCISE IS 1080 00:56:24,800 --> 00:56:27,320 WORKING, ACCUPUNCTURE, ACTIVATED 1081 00:56:27,320 --> 00:56:27,840 [INDISCERNIBLE], ACTIVATED 1082 00:56:27,840 --> 00:56:29,720 THROMBOW SIGHTS SO I THINK IT'S 1083 00:56:29,720 --> 00:56:31,200 CONSISTENT, SO STEM CELLS, SO 1084 00:56:31,200 --> 00:56:35,920 IT'S THERAPY WHICH LEADS TO 1085 00:56:35,920 --> 00:56:38,720 UPREGULATION OF OUR RESPONSE, 1086 00:56:38,720 --> 00:56:39,160 OUR IMMUNE RESPONSE. 1087 00:56:39,160 --> 00:56:41,680 AND YOU KNOW I WOULD LIKE, YEAH, 1088 00:56:41,680 --> 00:56:46,280 I WOULD LIKE MY NEXT STEPS WILL 1089 00:56:46,280 --> 00:56:48,120 BE TO STUDY HOW THESE THERAPIES 1090 00:56:48,120 --> 00:56:53,240 ARE WORKING BUT IT REALLY WORKS 1091 00:56:53,240 --> 00:56:55,560 THROUGH UPREGULATION OF OUR 1092 00:56:55,560 --> 00:56:56,720 NATURAL ADAPTIVE RESPONSE AND 1093 00:56:56,720 --> 00:56:58,560 YOU KNOW SO WHICH PATHWAY THIS 1094 00:56:58,560 --> 00:57:02,080 HAPPEN AND WHAT IS THE 1095 00:57:02,080 --> 00:57:07,320 CONSEQUENCE OF THESE PATHWAYS. 1096 00:57:07,320 --> 00:57:07,680 >> THANK YOU. 1097 00:57:07,680 --> 00:57:08,280 THANK YOU VERY MUCH. 1098 00:57:08,280 --> 00:57:12,440 IT SOUNDS INTERESTING AND IT 1099 00:57:12,440 --> 00:57:15,480 SOUNDS LIKE [INDISCERNIBLE] NOT 1100 00:57:15,480 --> 00:57:16,560 SO ADDITIONAL, ESPECIALLY IN THE 1101 00:57:16,560 --> 00:57:20,160 USA MEDICINE RIGHT NOW. 1102 00:57:20,160 --> 00:57:21,280 OKAY, OUR NEXT QUESTION, NEXT 1103 00:57:21,280 --> 00:57:26,200 QUESTION I HAVE FROM DR. TABAK, 1104 00:57:26,200 --> 00:57:30,640 AND DO YOU THINK THAT MODULATION 1105 00:57:30,640 --> 00:57:35,320 OF NK CELLS IN FIBRO MYALGIA 1106 00:57:35,320 --> 00:57:38,920 PATIENTS REDUCE DISEASE 1107 00:57:38,920 --> 00:57:39,840 PROGRESSION? 1108 00:57:39,840 --> 00:57:40,400 AMELIORATE THE SYMPTOMS? 1109 00:57:40,400 --> 00:57:43,200 >> IT'S A VERY GOOD QUESTION. 1110 00:57:43,200 --> 00:57:45,320 SO WE WERE ALSO THINKING ABOUT 1111 00:57:45,320 --> 00:57:46,800 THIS AND SO ORIGINALLY WE 1112 00:57:46,800 --> 00:57:52,400 THOUGHT THIS IS HOW WE NEED TO 1113 00:57:52,400 --> 00:57:54,160 TREAT CHRONIC PAIN BECAUSE WE 1114 00:57:54,160 --> 00:57:59,000 NEED TO ENHANCE NK CELLS. 1115 00:57:59,000 --> 00:58:05,000 AND MAYBE IT IS BUT THE PROBLEM 1116 00:58:05,000 --> 00:58:09,200 IS, LIKE, WHY NERVES MARK 1117 00:58:09,200 --> 00:58:11,720 THEMSELVES WITH THE NK CELL 1118 00:58:11,720 --> 00:58:12,000 RECEPTOR. 1119 00:58:12,000 --> 00:58:13,800 WHY NERVE SIGNAL TO NK CELLS 1120 00:58:13,800 --> 00:58:28,480 THAT THEY NEED TO BE REMOVED? 1121 00:58:28,480 --> 00:58:30,440 BECAUSE NK CELLS SUPPOSEDLY DO 1122 00:58:30,440 --> 00:58:32,280 THEIR JOB, THEY HAVE BEEN ASKED 1123 00:58:32,280 --> 00:58:35,480 TO COME AND THEY COME AND THEY 1124 00:58:35,480 --> 00:58:36,680 KILL THE NERVES RIGHT? 1125 00:58:36,680 --> 00:58:39,320 SO RIGHT NOW, I AM NO THINKING 1126 00:58:39,320 --> 00:58:44,440 THAT WE NEED TO FIGURE OUT WHY 1127 00:58:44,440 --> 00:58:47,840 SERVES EXPRESS RECEPTOR FOR NK 1128 00:58:47,840 --> 00:58:50,000 CELLS, SO RIGHT NOW, OUR THOUGHT 1129 00:58:50,000 --> 00:58:52,480 IS DEVELOPING ALONG WITH THIS 1130 00:58:52,480 --> 00:58:53,680 OTHER WHICH WE FIRST DIDN'T, YOU 1131 00:58:53,680 --> 00:58:56,400 KNOW DIDN'T HAVE TIME AND DIDN'T 1132 00:58:56,400 --> 00:58:58,440 PAY SO MUCH ATTENTION WITH THE 1133 00:58:58,440 --> 00:59:00,840 B-CELLS, INCREASE IN B-CELLS AND 1134 00:59:00,840 --> 00:59:06,400 INCREASE OF THE OUTING AND THIS 1135 00:59:06,400 --> 00:59:10,400 RECENT PAPER, IN NCI WITH A BIG 1136 00:59:10,400 --> 00:59:12,160 RESEARCHERS WHICH SHOWED THAT 1137 00:59:12,160 --> 00:59:14,680 FIBRO MYALGIA PATIENT HAVE 1138 00:59:14,680 --> 00:59:16,400 [INDISCERNIBLE] CELLS IN DRGs 1139 00:59:16,400 --> 00:59:19,600 SO YOU KNOW IN WHAT WE WOULD 1140 00:59:19,600 --> 00:59:24,800 LIKE TO SEE IF THIS IS THE 1141 00:59:24,800 --> 00:59:27,200 REASON WHY THE NERVE DEVELOP 1142 00:59:27,200 --> 00:59:29,840 EXPRESS RECEPTOR FOR NK CELLS 1143 00:59:29,840 --> 00:59:32,720 BECAUSE THERE IS SOMEHOW 1144 00:59:32,720 --> 00:59:38,200 ACTIVATED, THEY GENERATED BY 1145 00:59:38,200 --> 00:59:39,800 THIS SATELLITE CELLS, SENSING 1146 00:59:39,800 --> 00:59:42,240 NEURONS SO I'M SORRY, IT'S A 1147 00:59:42,240 --> 00:59:43,600 LONG ANSWER BUT I GUESS THE 1148 00:59:43,600 --> 00:59:44,040 SHORT 1. 1149 00:59:44,040 --> 00:59:44,520 IESM NOT SURE. 1150 00:59:44,520 --> 00:59:45,480 I DON'T THINK SO. 1151 00:59:45,480 --> 00:59:47,960 I THINK WE NEED TO LOOK UPSTREAM 1152 00:59:47,960 --> 00:59:50,040 OF THE NK CELLS. 1153 00:59:50,040 --> 00:59:50,480 >> THANK YOU. 1154 00:59:50,480 --> 00:59:57,480 NEXT 2 QUESTIONS I HAVE FROM OUR 1155 00:59:57,480 --> 00:59:58,800 AUDIENCE, FIRST 1, UPON 1156 00:59:58,800 --> 01:00:01,440 [INDISCERNIBLE] FOR OTHER 1157 01:00:01,440 --> 01:00:02,080 NEUROLOGICAL DISEASES? 1158 01:00:02,080 --> 01:00:05,600 IT'S WELL KNOWN THAT CHRONIC 1159 01:00:05,600 --> 01:00:08,800 PAIN IS CO MORBIDITY DEPRESSION, 1160 01:00:08,800 --> 01:00:12,000 WHAT HAPPENS IN FMS THAT LEADS 1161 01:00:12,000 --> 01:00:17,160 TO [INDISCERNIBLE] NK CELLS? 1162 01:00:17,160 --> 01:00:23,160 >> SO THE NK CELLS OR 1163 01:00:23,160 --> 01:00:25,280 [INDISCERNIBLE]? 1164 01:00:25,280 --> 01:00:25,920 >> ACTIVATED NK CELLS. 1165 01:00:25,920 --> 01:00:27,400 >> IN THE BEGINNING OF THE 1166 01:00:27,400 --> 01:00:27,680 QUESTION? 1167 01:00:27,680 --> 01:00:33,200 >> BEGINNING OF THE QUESTION, 1168 01:00:33,200 --> 01:00:35,160 ARE SNPs RECEPTOR FOUND FOR 1169 01:00:35,160 --> 01:00:36,000 OTHER NEUROLOGICAL DISEASES? 1170 01:00:36,000 --> 01:00:37,520 >> OKAY, OKAY, SO LET'S STOP 1171 01:00:37,520 --> 01:00:39,160 HERE BECAUSE IT'S 2 DIFFERENT 1172 01:00:39,160 --> 01:00:40,840 QUESTION, RIGHT? 1173 01:00:40,840 --> 01:00:45,480 SO THERE'S NK AND--THEY ACTUALLY 1174 01:00:45,480 --> 01:00:45,800 NOT RELATED. 1175 01:00:45,800 --> 01:00:48,000 YEAH, SO BECAUSE I PROBABLY 1176 01:00:48,000 --> 01:00:50,480 SHOULD HAVE, YOU KNOW TELL 1177 01:00:50,480 --> 01:00:52,160 EVERYBODY, WELL, I'M NOT YET CAN 1178 01:00:52,160 --> 01:00:54,240 CONNECT ALL THE DOTS BUT YOU 1179 01:00:54,240 --> 01:01:02,160 KNOW I CAN FIND-- 1180 01:01:02,160 --> 01:01:04,280 >> YEAH, OKAY. 1181 01:01:04,280 --> 01:01:05,560 >> SO YEAH, [INDISCERNIBLE] 1182 01:01:05,560 --> 01:01:06,840 RECEPTOR JUST AS WE'VE SEEN 1183 01:01:06,840 --> 01:01:08,920 RECENTLY HAS BEEN IN THE 1184 01:01:08,920 --> 01:01:12,000 [INDISCERNIBLE] THE LAST 2 YEARS 1185 01:01:12,000 --> 01:01:14,520 BIG TIME TO DEPRESSION, 1186 01:01:14,520 --> 01:01:17,880 SCHIZOPHRENIA AND MANY OTHER 1187 01:01:17,880 --> 01:01:20,200 NEUROLOGICAL DISEASES, SO YEAH, 1188 01:01:20,200 --> 01:01:22,080 IT WOULD EXPLAIN AND 1189 01:01:22,080 --> 01:01:24,960 OTHER--ACTUALLY NEAR THE 1190 01:01:24,960 --> 01:01:26,720 DEGENERATIVE DISEASES. 1191 01:01:26,720 --> 01:01:28,280 SO IT'S DEFINITELY--DEFINITELY 1192 01:01:28,280 --> 01:01:30,920 WILL BE IN LINE WITH CO 1193 01:01:30,920 --> 01:01:39,560 MORBIDITY BETWEEN CHRONIC PAIN 1194 01:01:39,560 --> 01:01:41,600 AND NEUROLOGICAL 1195 01:01:41,600 --> 01:01:43,120 [INDISCERNIBLE]. 1196 01:01:43,120 --> 01:01:43,520 >> OKAY. 1197 01:01:43,520 --> 01:01:44,800 >> AND THE SECOND QUESTION WAS 1198 01:01:44,800 --> 01:01:52,080 ABOUT NK CELLS, RIGHT? 1199 01:01:52,080 --> 01:01:55,400 >> YES, UNLESS THERE NEEDS TO BE 1200 01:01:55,400 --> 01:01:56,440 ACTIVATED ARE NK CELLS? 1201 01:01:56,440 --> 01:01:57,120 >> YEAH, YEAH, EXCELLENT 1202 01:01:57,120 --> 01:01:57,400 QUESTION. 1203 01:01:57,400 --> 01:01:58,200 I DO NOT KNOW. 1204 01:01:58,200 --> 01:02:01,320 I DO NOT KNOW. 1205 01:02:01,320 --> 01:02:02,840 I WISH--AND SO, THAT'S WHY WE 1206 01:02:02,840 --> 01:02:04,680 PUBLISH IT IN PAIN BECAUSE WE 1207 01:02:04,680 --> 01:02:06,600 SPENT A LOT OF TIME TRYING TO 1208 01:02:06,600 --> 01:02:14,360 FIGURE OUT WHAT'S HAPPENED IN 1209 01:02:14,360 --> 01:02:16,800 FIBRO MYALGIA PATIENTS WHY THEY 1210 01:02:16,800 --> 01:02:17,320 ATTRACT NK CELLS. 1211 01:02:17,320 --> 01:02:19,280 YEAH. 1212 01:02:19,280 --> 01:02:20,480 WE DON'T KNOW. 1213 01:02:20,480 --> 01:02:22,400 , OKAY. 1214 01:02:22,400 --> 01:02:26,360 NEXT QUESTION IS FOR 1215 01:02:26,360 --> 01:02:27,000 DR. [INDISCERNIBLE], MESSAGE IS 1216 01:02:27,000 --> 01:02:33,520 DID YOU LOOK FOR SIGNS OF 1217 01:02:33,520 --> 01:02:35,480 MICROBIOTA IN [INDISCERNIBLE] 1218 01:02:35,480 --> 01:02:37,400 FOR EXAMPLE, DNA IN THE BLOOD, 1219 01:02:37,400 --> 01:02:40,720 SAMPLES OF PEOPLE WITH CHRONIC 1220 01:02:40,720 --> 01:02:41,400 PAIN? 1221 01:02:41,400 --> 01:02:42,960 >> NO, I'M WONDERING, MAYBE WE 1222 01:02:42,960 --> 01:02:46,040 CAN TALK LATER, I AM WOBDERRING 1223 01:02:46,040 --> 01:02:48,000 WHY YOU ASK [INDISCERNIBLE], 1224 01:02:48,000 --> 01:02:51,280 WAWE TRY TO LOOK IS FOR THE 1225 01:02:51,280 --> 01:02:51,560 VIRUSES. 1226 01:02:51,560 --> 01:02:55,040 WE TRY TO LOOK FOR THE VIRUSES 1227 01:02:55,040 --> 01:02:55,680 ESPECIALLY BETWEEN--BECAUSE OF 1228 01:02:55,680 --> 01:02:59,600 THE RESPONSE TO THE VIRUS IN OUR 1229 01:02:59,600 --> 01:03:04,920 RNA, FULL RNA SEQ DATA SET WAS 1230 01:03:04,920 --> 01:03:07,280 ALSO TOP SO WE MUST--THIS WILL 1231 01:03:07,280 --> 01:03:09,640 EXPLAIN OKAY, THERE IS A VIRAL 1232 01:03:09,640 --> 01:03:11,480 INFECTION IN SENSORY NEURONS AND 1233 01:03:11,480 --> 01:03:13,360 IN SENSORY NEURON EXPRESSED 1234 01:03:13,360 --> 01:03:15,040 RECEPTOR NEAR NK CELLS AND NK 1235 01:03:15,040 --> 01:03:20,640 CELLS COMES IN [INDISCERNIBLE], 1236 01:03:20,640 --> 01:03:23,520 BUT THE PROBLEM IS IN THE BLOT 1237 01:03:23,520 --> 01:03:37,000 WE DIDN'T FIND VIRUSES, LIKE NK 1238 01:03:37,000 --> 01:03:37,600 RESPONSE--GO CHECK. 1239 01:03:37,600 --> 01:03:39,920 BUT, YEAH THIS WILL BE 1240 01:03:39,920 --> 01:03:42,400 CONSISTENT WITH VIRAL APPROACHES 1241 01:03:42,400 --> 01:03:45,040 TO FIBRO MYALGIA WHICH HAS BEEN 1242 01:03:45,040 --> 01:03:46,600 PROPOSED FROM DIFFERENT ANGLES 1243 01:03:46,600 --> 01:03:52,040 IN THE LAST 20 YEARS. 1244 01:03:52,040 --> 01:03:54,640 >> AND 1 MORE QUESTION IS HERE 1245 01:03:54,640 --> 01:03:59,000 FOR YOU, IT LOOKS LIKE MORE 1246 01:03:59,000 --> 01:03:59,960 TECHNICAL, DURING SOME PART OF 1247 01:03:59,960 --> 01:04:03,600 THE TALK, MAYBE I MISS THIS BUT 1248 01:04:03,600 --> 01:04:04,520 WHERE ARE PATIENTS 1249 01:04:04,520 --> 01:04:06,320 [INDISCERNIBLE] ON THE SAME 1250 01:04:06,320 --> 01:04:07,520 TREATMENT? 1251 01:04:07,520 --> 01:04:09,200 YOU SAY [INDISCERNIBLE] WHERE'S 1252 01:04:09,200 --> 01:04:12,400 THE TREATMENT CORRELATES THESE 1253 01:04:12,400 --> 01:04:12,640 OUTCOME? 1254 01:04:12,640 --> 01:04:18,080 AND WHERE WILL THE TREATMENTS 1255 01:04:18,080 --> 01:04:20,600 INVOLVE IMMUNE REGULATION? 1256 01:04:20,600 --> 01:04:23,000 >> EXCELLENT QUESTION. 1257 01:04:23,000 --> 01:04:25,040 I WOULD REVIEWER DEFINITELY ASK 1258 01:04:25,040 --> 01:04:26,800 THE SAME QUESTION, THE ANSWER IS 1259 01:04:26,800 --> 01:04:30,000 THIS, SO IT WASN'T CLINICAL 1260 01:04:30,000 --> 01:04:35,160 TRIAL, SO THE PATIENT WAS UNDER 1261 01:04:35,160 --> 01:04:37,000 STANDARD OF CARE TREATMENT AND 1262 01:04:37,000 --> 01:04:38,960 MODEL CITIZEN JORRITY OF THE 1263 01:04:38,960 --> 01:04:41,680 PATIENT WOULD GET NSAID OR 1264 01:04:41,680 --> 01:04:44,960 STEROIDS BUT NOT ALL OF THEM. 1265 01:04:44,960 --> 01:04:48,600 MANY PATIENTS ALSO GIVE OPIOIDS 1266 01:04:48,600 --> 01:04:50,480 AND ALL OTHER ANALGESIC BUT 1267 01:04:50,480 --> 01:04:52,240 USUALLY PEOPLE WITH ACUTE BACK 1268 01:04:52,240 --> 01:04:55,400 PAIN GET IT. 1269 01:04:55,400 --> 01:04:57,000 HOWEVER, YOU GET--WE LOOK AT 1270 01:04:57,000 --> 01:05:01,640 DATA ON THE DRUG USE FOR EACH 1271 01:05:01,640 --> 01:05:04,080 PATIENT BUT IT WAS NO 1272 01:05:04,080 --> 01:05:07,120 SIGNIFICANT ASSOCIATION WITH THE 1273 01:05:07,120 --> 01:05:13,360 DRUG USE IN THIS PATIENT AND IT 1274 01:05:13,360 --> 01:05:15,520 WAS NO ASSOCIATION REALLY WITH 1275 01:05:15,520 --> 01:05:16,800 THE INFLAMMATORY RESPONSE IN 1276 01:05:16,800 --> 01:05:19,680 THIS PATIENT AND SO, WHICH LEADS 1277 01:05:19,680 --> 01:05:26,160 ME TO THINK THAT ALTHOUGH LIKE 1278 01:05:26,160 --> 01:05:27,360 SEQ AND STEROID, LEAD TO 1279 01:05:27,360 --> 01:05:28,400 IMPAIRMENT OF THE IMMUNE 1280 01:05:28,400 --> 01:05:30,440 RESPONSE, THERE IS ALSO 1281 01:05:30,440 --> 01:05:33,440 INTRINSIC INABILITY OF SOME 1282 01:05:33,440 --> 01:05:37,000 PEOPLE TO UPREGULATE ADAPTIVE 1283 01:05:37,000 --> 01:05:37,840 RESPONSE. 1284 01:05:37,840 --> 01:05:40,560 AND IT'S ALSO LED TO ME THINK, 1285 01:05:40,560 --> 01:05:43,880 OKAY, SOME PEOPLE WHO TAKE AND 1286 01:05:43,880 --> 01:05:46,320 SEQ THEY DON'T COMPLETELY DOWN 1287 01:05:46,320 --> 01:05:48,720 REGULATE IMMUNE RESPONSE, THIS 1288 01:05:48,720 --> 01:05:53,480 WILL BE [INDISCERNIBLE] 1289 01:05:53,480 --> 01:05:54,280 REPUTATION [INDISCERNIBLE]. 1290 01:05:54,280 --> 01:05:55,320 >> I THINK WE HAVE TIME FOR THE 1291 01:05:55,320 --> 01:05:56,520 LAST QUESTION. 1292 01:05:56,520 --> 01:06:00,720 THE LAST QUESTION IS PRACTICES 1293 01:06:00,720 --> 01:06:04,200 PROFESSOR DAVID WHI TCOMB AND 1294 01:06:04,200 --> 01:06:05,800 WHAT IS THE LAB [INDISCERNIBLE] 1295 01:06:05,800 --> 01:06:09,960 CHRONIC PAIN AND DEPRESSION, FOR 1296 01:06:09,960 --> 01:06:10,640 GENERAL ANXIETY DISORDERS? 1297 01:06:10,640 --> 01:06:11,040 >> REALLY HARD. 1298 01:06:11,040 --> 01:06:13,280 I DON'T REMEMBER ON THE TOP OF 1299 01:06:13,280 --> 01:06:16,240 MY HEAD, BUT BASICALLY 1300 01:06:16,240 --> 01:06:20,320 DEPRESSION IS 1 OF THE MAJOR 1301 01:06:20,320 --> 01:06:21,760 FACTOR AFTER PRESENCE OF 1302 01:06:21,760 --> 01:06:28,400 [INDISCERNIBLE] CHRONIC PAIN 1303 01:06:28,400 --> 01:06:28,960 CONDITION. 1304 01:06:28,960 --> 01:06:29,200 >> OKAY. 1305 01:06:29,200 --> 01:06:33,640 THEN THE MOST LAST QUESTION FOR 1306 01:06:33,640 --> 01:06:33,920 YOU. 1307 01:06:33,920 --> 01:06:35,400 YOU SHOW QUITE ROBUST WITH 1308 01:06:35,400 --> 01:06:36,400 INFLAMMATION AND PAIN 1309 01:06:36,400 --> 01:06:38,240 [INDISCERNIBLE] WHY DO YOU SEE 1310 01:06:38,240 --> 01:06:42,880 SCIENTISTS DID NOT OBSERVE IT 1311 01:06:42,880 --> 01:06:43,200 PREVIOUSLY? 1312 01:06:43,200 --> 01:06:44,800 >> YEAH, SO WE WERE THINKING 1313 01:06:44,800 --> 01:06:46,400 ABOUT THIS, TOO, LIKE HOW COME 1314 01:06:46,400 --> 01:06:48,600 YOU CAN MISS IT, RIGHT? 1315 01:06:48,600 --> 01:06:51,600 IT'S BLACK AND WHITE HOW YOU CAN 1316 01:06:51,600 --> 01:06:52,480 LIKE--SPECIFICALLY PUT THIS 1317 01:06:52,480 --> 01:06:56,400 SLIDE, YEAH, AND I THINK IT'S 1318 01:06:56,400 --> 01:07:05,840 BECAUSE THE WAY HOW WE STUDY THE 1319 01:07:05,840 --> 01:07:07,120 WAY WE BELIEF THE PAIN PROGRESS 1320 01:07:07,120 --> 01:07:09,760 BECAUSE I THINK I ALREADY 1321 01:07:09,760 --> 01:07:11,520 MENTIONED THIS, I THINK WE FIRST 1322 01:07:11,520 --> 01:07:14,120 OF ALL WE CONSTANTLY STUDIED 1323 01:07:14,120 --> 01:07:16,600 PEOPLE WHO HAVE PAIN, SO IN THIS 1324 01:07:16,600 --> 01:07:18,000 SLIDE IS THIS PEOPLE. 1325 01:07:18,000 --> 01:07:21,600 OKAY, IF YOU DON'T HAVE ANY 1326 01:07:21,600 --> 01:07:23,000 SIGNIFICANT DIFFERENCE, WE 1327 01:07:23,000 --> 01:07:24,320 CANNOT--IT'S DIFFICULT TO LEARN 1328 01:07:24,320 --> 01:07:25,400 SOMETHING FROM THIS. 1329 01:07:25,400 --> 01:07:30,720 YEAH, BECAUSE IT'S ABSENCE OF 1330 01:07:30,720 --> 01:07:31,600 THE FACT. 1331 01:07:31,600 --> 01:07:34,120 WE CONSTANTLY ARE LOOKING FOR 1332 01:07:34,120 --> 01:07:36,640 WHAT WENT WRONG IN THE PEOPLE 1333 01:07:36,640 --> 01:07:37,440 WITH CHRONIC PAIN. 1334 01:07:37,440 --> 01:07:40,760 AND IT'S, YEAH, SO FAR I DON'T 1335 01:07:40,760 --> 01:07:41,840 THINK PEOPLE'S VERY SUCCESSFUL 1336 01:07:41,840 --> 01:07:46,040 UPON BUT OUR STUDIES SHOW THAT 1337 01:07:46,040 --> 01:07:47,920 IF WE ASK A QUESTION, WHAT WENT 1338 01:07:47,920 --> 01:07:50,600 RIGHT IN THE PEOPLE WHO DID 1339 01:07:50,600 --> 01:07:53,560 RESOLVE PAIN, THERE IS SO MUCH 1340 01:07:53,560 --> 01:07:54,760 INFORMATION THAT, YOU WE 1341 01:07:54,760 --> 01:07:56,680 DEFINITELY CAN HAVE SOMETHING TO 1342 01:07:56,680 --> 01:07:57,520 CHEW ON. 1343 01:07:57,520 --> 01:07:59,440 >> OKAY, I SEE YOUR PINT. 1344 01:07:59,440 --> 01:08:00,000 THANK YOU. 1345 01:08:00,000 --> 01:08:00,440 THANK YOU VERY MUCH. 1346 01:08:00,440 --> 01:08:02,000 DOCTOR I WANT TO THANK YOU AGAIN 1347 01:08:02,000 --> 01:08:04,400 FOR YOUR WONDERFUL TALK AND I 1348 01:08:04,400 --> 01:08:06,480 ALSO WANT TO SAY HOW PROUD WE 1349 01:08:06,480 --> 01:08:11,000 ARE TO HAVE SPONSORED THIS 1350 01:08:11,000 --> 01:08:13,120 PRESENTATION HERE IN THE NIH 1351 01:08:13,120 --> 01:08:13,920 WEDNESDAY AFTERNOON LECTURE 1352 01:08:13,920 --> 01:08:15,120 SERIES AND WE WERE PLEASED TO 1353 01:08:15,120 --> 01:08:17,360 HEAR ABOUT THE GREAT ADVANCES 1354 01:08:17,360 --> 01:08:18,840 AND ESPECIALLY ABOUT YOUR 1355 01:08:18,840 --> 01:08:21,200 ACHIEVEMENTS IN THE SUCCESS OF 1356 01:08:21,200 --> 01:08:24,000 YOUR COLLEAGUES IN UNDERSTANDING 1357 01:08:24,000 --> 01:08:25,400 OF CHRONIC PAIN. 1358 01:08:25,400 --> 01:08:26,720 IT WAS ALSO A PLEASURE TO LEARN 1359 01:08:26,720 --> 01:08:29,600 MORE ABOUT THE MECHANISM IN THE 1360 01:08:29,600 --> 01:08:34,200 REGULATION OF CHRONIC PAIN AND 1361 01:08:34,200 --> 01:08:37,800 THE FUTURE [INDISCERNIBLE] THANK 1362 01:08:37,800 --> 00:00:00,000 YOU FOR JOINING US.