Heritability of nociception I: Responses of 11 inbred mouse strains on 12 measures of nociception Jeffrey S. Mogil a, *, Sonya G. Wilson a , Karine Bon a , Seo Eun Lee b , Kyungsoon Chung b , Pnina Raber c , Jeanne O. Pieper d , Heather S. Hain e , John K. Belknap e , Lawrence Hubert a , Greg I. Elmer f , Jin Mo Chung b , Marshall Devor c a Department of Psychology and Neuroscience Program, University of Illinois at Urbana-Champaign, 603 East Daniel Street, Champaign, IL 61820, USA b Marine Biomedical Institute and Department of Anatomy and Neurosciences, University of Texas Medical Branch, Galveston, TX 77555, USA c Department of Cell and Animal Biology, Life Sciences Institute, Hebrew University of Jerusalem, 91904 Jerusalem, Israel d Behavioral Neuroscience Section, Intramural Research Program, NIDA, NIH, Baltimore, MD 21224, USA e Department of Behavioral Neuroscience and VA Medical Center, Oregon Health Sciences University, Portland, OR 97201, USA f Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228, USA Received 1 July 1998; received in revised form 1 September 1998; accepted 25 September 1998 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), mechan- ical 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 (h 2 = 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.  1999 International Association for the Study of Pain. Published by Elsevier Science B.V. Keywords: Algesiometry; Inbred strains; Mouse genetics; Pain models; Strain differences 1. Introduction A great deal of variability has been noted in pain responses among individual humans (e.g. Libman, 1934; Sherman, 1943; Beecher, 1946; Wolff et al., 1965; Chen et al., 1989), and across family and ethnic groups (e.g. Woodrow et al., 1972; Violon and Giurgea, 1984; Edwards et al., 1985; Bachiocco et al., 1993). Although this observa- tion is generally interpreted as reflecting shared socializa- tion rather than shared genes, it is also consistent with the possibility of genetic predisposition. It is particularly hazar- dous to ignore the possibility of constitutional effects on pain sensation in man in light of the emerging literature on the genetics of other complex psychosocial phenomena in humans, and of the growing body of information regard- ing pain genetics in animals. Pain 80 (1999) 67–82 0304-3959/99/$ - see front matter  1999 International Association for the Study of Pain. Published by Elsevier Science B.V. PII: S0304-3959(98)00197-3 * Corresponding author. Tel.: +1-217-333-6546; fax: +1-217-244-5876; e-mail: jmogil@s.psych.uiuc.edu