PMID- 16623937 OWN - NLM STAT- MEDLINE DCOM- 20061004 LR - 20211020 IS - 1744-8069 (Electronic) IS - 1744-8069 (Linking) VI - 2 DP - 2006 Apr 19 TI - A clinical genetic method to identify mechanisms by which pain causes depression and anxiety. PG - 14 AB - BACKGROUND: Pain patients are often depressed and anxious, and benefit less from psychotropic drugs than pain-free patients. We hypothesize that this partial resistance is due to the unique neurochemical contribution to mood by afferent pain projections through the spino-parabrachial-hypothalamic-amygdalar systems and their projections to other mood-mediating systems. New psychotropic drugs for pain patients might target molecules in such brain systems. We propose a method to prioritize molecular targets by studying polymorphic genes in cohorts of patients undergoing surgical procedures associated with a variable pain relief response. We seek molecules that show a significant statistical interaction between (1) the amount of surgical pain relief, and (2) the alleles of the gene, on depression and anxiety during the first postoperative year. RESULTS: We collected DNA from 280 patients with sciatica due to a lumbar disc herniation, 162 treated surgically and 118 non-surgically, who had been followed for 10 years in the Maine Lumbar Spine Study, a large, prospective, observational study. In patients whose pain was reduced >25% by surgery, symptoms of depression and anxiety, assessed with the SF-36 Mental Health Scale, improved briskly at the first postoperative measurement. In patients with little or no surgical pain reduction, mood scores stayed about the same on average. There was large inter-individual variability at each level of residual pain. Polymorphisms in three pre-specified pain-mood candidate genes, catechol-O-methyl transferase (COMT), serotonin transporter, and brain-derived neurotrophic factor (BDNF) were not associated with late postoperative mood or with a pain-gene interaction on mood. Although the sample size did not provide enough power to persuasively search through a larger number of genes, an exploratory survey of 25 other genes provides illustrations of pain-gene interactions on postoperative mood--the mu opioid receptor for short-term effects of acute sciatica on mood, and the galanin-2 receptor for effects of unrelieved post-discectomy pain on mood one year after surgery. CONCLUSION: Genomic analysis of longitudinal studies of pain, depression, and anxiety in patients undergoing pain-relieving surgery may help to identify molecules through which pain alters mood. Detection of alleles with modest-sized effects will require larger cohorts. FAU - Max, Mitchell B AU - Max MB AD - Clinical Pain Research Section, Division of Intramural Research, National Institute of Dental and Craniofacial Research, National Institutes of Health, DHHS, Bethesda, MD, USA. mm77k@nih.gov FAU - Wu, Tianxia AU - Wu T FAU - Atlas, Steven J AU - Atlas SJ FAU - Edwards, Robert R AU - Edwards RR FAU - Haythornthwaite, Jennifer A AU - Haythornthwaite JA FAU - Bollettino, Antonella F AU - Bollettino AF FAU - Hipp, Heather S AU - Hipp HS FAU - McKnight, Colin D AU - McKnight CD FAU - Osman, Inge A AU - Osman IA FAU - Crawford, Erin N AU - Crawford EN FAU - Pao, Maryland AU - Pao M FAU - Nejim, Jemiel AU - Nejim J FAU - Kingman, Albert AU - Kingman A FAU - Aisen, Daniel C AU - Aisen DC FAU - Scully, Michele A AU - Scully MA FAU - Keller, Robert B AU - Keller RB FAU - Goldman, David AU - Goldman D FAU - Belfer, Inna AU - Belfer I LA - eng GR - K24 NS02225/NS/NINDS NIH HHS/United States GR - K24 NS002225/NS/NINDS NIH HHS/United States GR - Z01 DE000366/ImNIH/Intramural NIH HHS/United States GR - K23 AR051315/AR/NIAMS NIH HHS/United States GR - Z01 AA000301/ImNIH/Intramural NIH HHS/United States GR - P60 AR048094/AR/NIAMS NIH HHS/United States GR - HS-08194/HS/AHRQ HHS/United States GR - R01 HS009804/HS/AHRQ HHS/United States GR - HS-09804/HS/AHRQ HHS/United States GR - HS-06344/HS/AHRQ HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, N.I.H., Intramural PT - Research Support, U.S. Gov't, P.H.S. DEP - 20060419 PL - United States TA - Mol Pain JT - Molecular pain JID - 101242662 RN - 0 (Psychotropic Drugs) RN - 0 (Receptor, Galanin, Type 2) RN - 0 (Receptors, Opioid, mu) SB - IM MH - Anxiety Disorders/*genetics/physiopathology/psychology MH - Cohort Studies MH - DNA Mutational Analysis/methods MH - Depressive Disorder/*genetics/physiopathology/psychology MH - Drug Resistance/*genetics MH - Gene Frequency/genetics MH - Genetic Predisposition to Disease/*genetics MH - Genetic Testing/methods MH - Genetic Variation/genetics MH - Genotype MH - Humans MH - Intervertebral Disc Displacement/genetics/physiopathology/psychology MH - Mutation/genetics MH - Pain/*complications/*genetics/psychology MH - Polymorphism, Genetic/genetics MH - Prospective Studies MH - Psychotropic Drugs/pharmacology MH - Receptor, Galanin, Type 2/genetics MH - Receptors, Opioid, mu/genetics MH - Sciatica/complications/genetics/psychology PMC - PMC1488826 EDAT- 2006/04/21 09:00 MHDA- 2006/10/05 09:00 PMCR- 2006/04/19 CRDT- 2006/04/21 09:00 PHST- 2006/03/06 00:00 [received] PHST- 2006/04/19 00:00 [accepted] PHST- 2006/04/21 09:00 [pubmed] PHST- 2006/10/05 09:00 [medline] PHST- 2006/04/21 09:00 [entrez] PHST- 2006/04/19 00:00 [pmc-release] AID - 1744-8069-2-14 [pii] AID - 10.1186/1744-8069-2-14 [doi] PST - epublish SO - Mol Pain. 2006 Apr 19;2:14. doi: 10.1186/1744-8069-2-14.