Mapping a gene for neuropathic pain-related behavior following peripheral neurectomy in the mouse.
Total hindpaw denervation in rodents elicits an abnormal behavior of licking, scratching and self-injury of the anesthetic limb ("autotomy"). Since the same denervation produces phantom limb pain and anesthesia dolorosa in humans, autotomy has been used as a model of human neuropathic pain. Autotomy is an inherited trait in rodents, attributable to a few genes of major effect. Here we used recombinant inbred (RI) mouse lines of the AXB-BXA RI set to map a gene for autotomy. Autotomy levels following unilateral sciatic and saphenous nerve section were scored daily for 36 days, using a standardized scale, in all 23 RI lines available for this set. We used a genetic map of 395 marker loci and a permutation-based statistical method for categorical data to assess the statistical significance of mapping results. We identified a marker on chromosome 15 with statistical support (P=0.0003) in the range considered significant for genome-wide scans in the mouse. Several genes located in this chromosomal region encode for neural functions related to neuropathic pain and may indicate targets for development of novel analgesics.
Seltzer
Ze'ev
Z
Department of Physiology, Faculties of Medicine and Dental Medicine, Hebrew University, P.O. Box 11720, 91120 Jerusalem, Israel Craniofacial Epidemiology and Genetics Branch, National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, USA Pain and Neurosensory Mechanisms Branch, National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, USA.
Wu
Tianxia
T
Max
Mitchell B
MB
Diehl
Scott R
SR
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001947:Breeding; D002874:Chromosome Mapping; D003714:Denervation; D005260:Female; D008040:Genetic Linkage; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D009437:Neuralgia / Q000235:genetics*; D010591:Phantom Limb / Q000235:genetics*; D012584:Sciatic Nerve / Q000502:physiology; D013045:Species Specificity