Chronic musculoskeletal pain is a significant clinical problem that affects a large percent of the population and has a major economic impact on the health care system. Despite the clinical significance mechanisms underlying the development and maintenance of persistent pain conditions arising from deep tissue, and cellular mechanisms involved in the transition from acute to chronic pain conditions are not clearly understood. The overarching goal of my research is to elucidate cellular and molecular mechanisms of acute and persistent muscle and joint pain.

We are currently working on two major projects funded by NIH: (1) Investigate the role of peripheral receptor systems in overt muscle nociception and in mechanical hyperalgesia: Specifically, we have been investigating potential mechanisms that underlie the development of mechanical hyperalgesia with a particular emphasis on functional coupling between peripherally localized NMDA and metabotropic glutamate receptors and TRPV1 and TRPA1 channels. More recently, we introduced intriguing hypotheses that masseter inflammation induces alterations in DNA methylation, a prototype epigenetic mechanism, that lead to an increase in functional expression of multiple pro-nociceptive genes in trigeminal ganglia (TG), and that oxidative metabolites within TG is a key link between peripheral inflammation, psychophysical stress and the epigenetic modulation of pro-nociceptive genes. We implemented innovative experimental approaches, including gene specific modulation of DNA methylation using a CRISPR-dCAS9 based epigenome editing tool, to test our hypotheses in a rodent model of orofacial myositis.

(2) Study the factors that contribute to age- and sex-differences in molecular, cellular, and functional properties in antinociceptive systems that include opioid receptors, cannabinoid receptors and potassium channels: Specifically, we are investigating whether age-dependent changes in testosterone play a key role in regulating opioid receptor expression and function. We use a multidisciplinary experimental approach to investigate age-related changes in the efficacy of peripherally and centrally administered opioid in a rodent model of osteoarthritis with the goal of extending the use of peripherally administered opioids for pain management in the elderly.

We are also investigating androgen receptor and sex determining region Y, a male specific gene, as important factors mediating sex differences in endogenous pain modulation under inflammatory orofacial pain condition. The knowledge gained from this project will expand the basic research on hormonal, environmental, as well as genetic factors as the underlying mechanisms of sex differences on central pain modulation and promises to provide a rationale for the development of gender specific treatment strategies.

KEY WORDS
Muscle, Inflammation, Peripheral Sensitization, DNA Methylation, TRP Channels, Opioid Receptors, Cannabinoid Receptors, Androgen Receptor, Sex Hromones, Age, Osteoarthritis