The Pain Genetics Lab is broadly interested in physiological mechanisms mediating the perception and inhibition of pain. Pain is a complex, subjective experience that displays considerable variability compared to other sensory modalities. In some instances and in some people, intensely noxious stimuli are not reported as causing pain, whereas others can experience excruciating pain from light touching of the skin. Some people are highly sensitive to pain relief from placebo administration, while others are insensitive to even high doses of morphine. Following nerve injury, only a small proportion of people go on to develop chronic, neuropathic pain.
Research in the Pain Genetics Lab revolves around a central question: why aren't we all alike in our sensitivity to pain, sensitivity to pain-killing drugs, and susceptibility to developing chronic pain? This inter-individual variability is, of course, a result of genetic factors (including biological sex), environmental factors, and the interaction of the two. Thus, the Lab performs studies of Pain Genetics, Sex Differences in Pain and Analgesia, and Environmental Factors Influencing Pain Sensitivity (especially laboratory stressors and social factors). Our studies are usually performed in the laboratory mouse, but increasingly we test the relevance of our findings in rats and humans as well. Since the findings are only as strong as the validity and clinical relevance of the animal models and measures will allow, another current focus of the laboratory involves the assessment of existing pain models and the development of new ones.
We use a multidisciplinary approach ranging from the molecular level (DNA-based gene mapping, RNA-based gene expression assays) to the cellular/systems level (immunohistochemistry, pharmacology) to the behavioural level (characterization of inbred mouse strains and transgenic knock-out mice). Recent experiments have implicated particular genes (e.g., Mc1r, encoding the melanocortin-1 receptor; Calca, encoding the calcitonin gene-related peptide; Atp1b3, encoding the beta-3 subunit of the sodium-potassium pump; Avpr1a, encoding the vasopressin-1A receptor; P2rx7, encoding the purinergic P2X7 receptor; Chrna6, encoding the alpha-6 subunit of the nicotinic receptor) and particular laboratory environmental factors (e.g., experimenter sex, order-of-testing, social interactions) in pain and analgesic variability. Of particular interest is the identification of sex-specific genes underlying pain sensitivity and analgesic sensitivity in mice. The laboratory has recently shown that in humans as in mice the two sexes possess qualitatively different neural mechanisms underlying the modulation of pain; much ongoing work is devoted to the characterization of this sex-specific neural circuitry.