Pain continues to be a major health problem with tremendous financial, social and psychological costs. Conservative estimates put the cost of pain to the US economy well into the hundreds of billions of dollars per year as a result of associated medical expenses and lost wages with a significant minority of Americans suffering from persistent or recurrent pain syndromes throughout the most productive years of their lives. Just one pain syndrome, migraine headache, directly impacts 20% of the adult population. Yet, there remain few if any effective therapies devoid of serious side effects that are currently available to treat pain, particularly persistent or recurrent pain associated with syndromes.
The clinical features of a number of pain syndromes serve as the organizing focus of research in the Gold laboratory. These observations include the following: 1) many pain syndromes are unique to a particular part of the body such as the head in migraine, the temporomandibular joint in temporomandibular disorder (TMD), or the colon in inflammatory bowel disease (IBD); 2) many pain syndromes such as migraine, TMD and IBD occur with a greater prevalence, severity and/or duration in women than in men; 3) many pain syndromes are associated with changes in the excitability of primary afferent neurons; 4) there are time dependent changes in the mechanisms underlying pain syndromes; and 5) the type of injury, (i.e., inflammation or nerve injury), are differentially sensitive to therapeutic interventions. These observations led to specific hypotheses that are tested in ongoing studies in the Gold laboratory. These include 1) characterizing the mechanisms underlying inflammation-induced changes in the evoked Ca2+ transients in sensory neurons, 2) characterizing the mechanisms underlying the initiation of migraine attacks, 3) characterizing the influence of estrogen on the excitability of spinal and trigeminal ganglion neurons, 4) characterizing the role of changes in inhibitory receptors, in particular GABA, in injury-induced increases in sensitivity, and 5) identification of ways to maximize the therapeutic utility of local anesthetics. The ultimate goal of these studies is to identify novel targets for the development of therapeutic interventions for the treatment of pain.
Liu Q and Gold MS (2016) Opioid Induced Loss of Local Anesthetic Potency in the Rat Sciatic Nerve. Anesthesiology. 125(4): 755-66 PMCID: PMC5030162
Saloman JL, Scheff NN, Snyder LM, Ross SE, Davis BM, and Gold MS (2016) Gi-DREADD expression in peripheral nerves produces ligand-dependent analgesia, as well as ligand-independent functional changes in sensory neurons. J Neurosci. 36(42): 10769-81 PMCID: PMC5083007
McIlvried LA, Cruz JA, Borghesi LA and Gold MS (2017) Sex-, stress-, and sympathetic post-ganglionic-dependent changes in identity and proportions of immune cells in the dura. Cephalagia. 37(1): 36-48. PMCID: PMC502350
Yilmaz E, Watkins S and Gold MS (2017) Paclitaxel-induced increase in mitochondrial volume mediates dysregulation of intracellular Ca2+ in putative nociceptive glabrous skin neurons from the rat. Cell Calcium. 62: 16-28. PMCID: PMC5365154
Shiwarski DJ, Tipton A, Schmidt BF, Giraldo MD, Gold MS, Pradhan AA, and Puthenveedu MA (2017) A phosphoinositide-regulated Golgi checkpoint regulates the bioavailability of delta opioid receptors. J Neurosci. 37(14): 3741-3752. PMCID: PMC5394893
Zhang XL, Priest BT, Belfer I and Gold MS (2017) Voltage-Gated Na+ Currents in Human Dorsal Root Ganglion Neurons. eLife. 16;6. PMCID: PMC5433841
Lim G, Farrell LM, Facco FL, Gold MS and Wasan A (2018) Labor Pain Relief Is a Predictor for Reduced Postpartum Depression Scores: Explaining the Relationship Between Labor Epidural Analgesia and Postpartum Depression Risk. Analgesia and Anesthesia. 126(5): 1598-1605
Hachisuka J, Omori Y, Chiang MC, Gold MS, Koerber HR, Ross SE (2018) Wind-up in lamina I spinoparabrachial neurons: a role for reverberatory circuits. PAIN. 159(8): 1484-1493
Snyder LM, Chiang MC, Loeza-Alcocer E, Omuri Y, Hachisuka J, Sheahan TD, Gale JR, Adelman PC, Sypek EI, Fulton SA, Friedman RL, Wright MC, Giraldo Duque M, Lee YS, Hu Z, Huang H, Cai X, Meerschaert KA, Nagarajan V, Hirai T, Scherrer G, Kaplan DH, Porreca F, Davis BM, Gold MS, Koerber HR, Ross SE (2018) Kappa Opioid Receptor Distribution and Function in Primary Afferents. Neuron. 99(6): 1274-88