Heritability of nociception. III. Genetic relationships among commonly used assays of nociception and hypersensitivity

Abstract

We and others have previously demonstrated that nociception in the mouse is heritable. A genetic correlation analysis of 12 common measures of nociception among a common set of inbred strains revealed three major clusters (or 'types') of nociception in this species. In the present study, we re-evaluated the major types of nociception and their interrelatedness using ten additional assays of nociception and hypersensitivity, including: three thermal assays (tail withdrawal from 47.5 degrees C water or -15 degrees C ethanol; tail flick from radiant heat), two chemical assays of spontaneous nociception (bee venom test; capsaicin test) and their subsequent thermal hypersensitivity states (including contralateral hypersensitivity in the bee venom test), a mechanical nociceptive assay (tail-clip test), and a mechanical hypersensitivity assay (intrathecal dynorphin). Confirming our earlier findings, the results demonstrate distinct thermal and chemical nociceptive types. It is now clear that mechanical hypersensitivity and thermal hypersensitivity are genetically dissociable phenomena. Furthermore, we now see at least two distinct types of thermal hypersensitivity: afferent-dependent, featuring a preceding significant period of spontaneous nociceptive behavior associated with afferent neural activity, and non-afferent-dependent. In conclusion, our latest analysis suggests that there are at least five fundamental types of nociception and hypersensitivity: (1) baseline thermal nociception; (2) spontaneous responses to noxious chemical stimuli; (3) thermal hypersensitivity; (4) mechanical hypersensitivity; and (5) afferent input-dependent hypersensitivity.

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities

“…When compared to other strains, C57BL/6J ("J" for Jackson Laboratory) mice became a popular animal model for pain studies as they exhibit a high basal nociceptive sensitivity 17,18 and a moderate analgesic response to opiates 14,19 . Following chronic morphine treatment, they also develop significant analgesic tolerance 20,21 , hyperalgesia 21,22 and dependence 20,23 .…”

Haplotype structure of inflammatory cytokines genes (IL1B, IL6 and TNF/LTA) in US Caucasians and African Americans

“…3 In addition, they are implicated in the pathophysiology of several diseases, a selection of which includes neurodegenerative disorders, 4 cardiovascular disease, 5 depression, 6 addictions 7 and pain. 8 Since these and other immune-related disorders are heritable, [9][10][11][12][13] it can be speculated that part of their genetic background is explained by genetic variation in inflammatory genes producing changes in the amount or structure of these genes. Therefore, genes encoding IL1b, IL6 and TNFa were screened for common functional polymorphisms for association and linkage studies.…”

Haplotype-based analysis of alpha 2A, 2B, and 2C adrenergic receptor genes captures information on common functional loci at each gene

“…It can be speculated that some of the interindividual variation in responses is explained by genetic variation in the receptors producing changes in the amount or structure of the receptors. In support of a role for genetic variation, several physiologic parameters modulated by adrenergic function are heritable, e.g., blood pressure (Mathias et al 2003), nociception (Lariviere et al 2002), mood, and anxiety (Johansson et al 2001).…”