Heritability of nociception I: Responses of 11 inbred mouse strains on 12 measures of nociception

It is generally acknowledged that humans display highly variable sensitivit y to pain, including variable responses to identical injuries or pathologie s, The possible contribution of genetic factors has, however, been largely overlooked. An emerging rodent literature documents the importance of genot ype in mediating basal nociceptive sensitivity, in establishing a predispos ition to neuropathic pain following neural injury, and in determining sensi tivity to pharmacological agents and endogenous antinociception. One clear finding from these studies is that the effect of genotype is at least parti ally specific to the nociceptive assay being considered. In this report we begin to systematically describe and characterize genetic variability of no ciception in a mammalian species, Mus musculus. We tested 11 readily-availa ble inbred mouse strains (129/J, A/J, AKR/J, BALB/cJ, C3H/HeJ, C57BL/6J, C5 8/J, CBA/J, DBA/2J, RIIIS/J and SM/J) using 12 common measures of nocicepti on. These included assays for thermal nociception (hot plate, Hargreaves' t est, tail withdrawal), mechanical nociception (von Frey filaments), chemica l nociception (abdominal constriction, carrageenan, formalin), and neuropat hic pain (autotomy, Chung model peripheral nerve injury). We demonstrate th e existence of clear strain differences in each assay, with 1.2 to 54-fold ranges of sensitivity. All nociceptive assays display moderate-to-high heri tability (h(2) = 0.30-0.76) and mediation by a limited number of apparent g enetic loci. Data comparing inbred strains have considerable utility as a t ool for understanding the genetics of nociception, and a particular relevan ce to transgenic studies. (C) 1999 international Association for the Study of Pain. Published by Elsevier Science B.V.