Mapping a gene for neuropathic pain-related behavior following peripheral neurectomy in the mouse

Total hindpaw denervation in rodents elicits an abnormal behavior of lickin g, scratching and self-injury of the anesthetic limb ('autotomy'). Since th e same denervation produces phantom limb pain and anesthesia dolorosa in hu mans, 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 eff ect. 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 a nd saphenous nerve section were scored daily for 36 days, using a standardi zed 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 categori cal data to assess the statistical significance of mapping results. We iden tified a marker on chromosome 15 with statistical support (P = 0.0003) in t he range considered significant for genome-wide scans in the mouse. Several genes located in this chromosomal region encode for neural functions relat ed to neuropathic pain and may indicate targets for development of novel an algesics. (C) 2001 Elsevier Science B.V. Published by Elsevier Science B.V. All rights reserved.