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

Abstract

It is generally acknowledged that humans display highly variable sensitivity to pain, including variable responses to identical injuries or pathologies. The possible contribution of genetic factors has, however, been largely overlooked. An emerging rodent literature documents the importance of genotype in mediating basal nociceptive sensitivity, in establishing a predisposition to neuropathic pain following neural injury, and in determining sensitivity to pharmacological agents and endogenous antinociception. One clear finding from these studies is that the effect of genotype is at least partially specific to the nociceptive assay being considered. In this report we begin to systematically describe and characterize genetic variability of nociception in a mammalian species, Mus musculus. We tested 11 readily-available inbred mouse strains (129/J, A/J, AKR/J, BALB/cJ, C3H/HeJ, C57BL/6J, C58/J, CBA/J, DBA/2J, RIIIS/J and SM/J) using 12 common measures of nociception. These included assays for thermal nociception (hot plate, Hargreaves' test, tail withdrawal), mechanical nociception (von Frey filaments), chemical nociception (abdominal constriction, carrageenan, formalin), and neuropathic pain (autotomy, Chung model peripheral nerve injury). We demonstrate the existence of clear strain differences in each assay, with 1.2 to 54-fold ranges of sensitivity. All nociceptive assays display moderate-to-high heritability (h2 = 0.30-0.76) and mediation by a limited number of apparent genetic loci. Data comparing inbred strains have considerable utility as a tool for understanding the genetics of nociception, and a particular relevance to transgenic studies.

Concentration-detection functions for eye irritation evoked by homologous n-alcohols and acetates approaching a cut-off point

“…One explanation considers the existence of genetic diversity regarding the exact structure and dimension(s) of chemesthetic receptors. Studies in animals have shown that genetic variability explains differences among individuals in their ability to detect nociceptive stimuli (Elmer et al 1998;Mogil et al 1999). Human psychophysical experiments on detection of nasal chemesthesis from VOCs showed that individual subjects might vary by one or two carbon units in the exact position of the cut-off homolog along a series but, once a subject reaches his or her cut-off, he or she never comes back to detect a larger molecule again .…”

Nanoparticle clearance is governed by Th1/Th2 immunity and strain background

“…However, far less work has been done to study the effects of biology on nanoparticle PK than the effects of material properties on nanoparticle PK. It is perhaps not surprising that we see different results in different mouse strains for clearance, as mouse strain background has a significant impact on biological processes ranging from immune function (42), pain sensation (43), and cancer (44). Outbred WT mice show a large degree of heterogeneity in many measures of immune function, while inbred lab strains of mice show very little intrastrain variation (45).…”

ASIC3 in muscle mediates mechanical, but not heat, hyperalgesia associated with muscle inflammation

“…Mogil and colleagues attempted to test the effects of muscle insult in their dominantnegative ASIC3 transgenic mice; however, the wild-type controls for ASIC3 transgenic mice do not develop mechanical hyperalgesia to repeated intramuscular acid injections (Mogil et al, 2005), as we previously described (Sluka et al, 2004). Differences are likely related to the strain of the mouse since prior studies demonstrate strain differences in mechanical sensitivity and in different injury-induced animal models of pain (Mogil et al, 1999a;Mogil et al, 1999b). In the current study we utilize congenic mice on a C57BL/6J background, while Mogil and colleagues (2005) utilize mice on an FVB background.…”