The molecular mechanisms underlying the development of opioid tolerance and dependence and the interactions of pain and analgesic signaling.
The primary focus of our research is to understand the molecular mechanisms underlying the development of opioid tolerance and dependence and the interactions of pain and analgesic signaling. We employ a multidisciplinary approach to understand these problems using cutting-edge techniques. After demonstrating clinical and physiological relevance in animal behavioral studies, we dissect mechanisms underlying opioid tolerance, physical dependence, and pain. We also aim to translate our findings into clinical trials and ultimately, better treatment for cancer patients.
The overall goal of these projects is to develop more effective therapies for treating chronic pain without causing the devastating side effects of tolerance, dependence, and addiction. Trainees gain experience integrating molecular, genetic, neuroanatomic, biochemical, and behavioral techniques to explore important neurobiological questions from many perspectives. Close relations with clinical colleagues in the pain clinic provide opportunities to translate our basic findings into clinical practice and eventually see the direct application of our efforts. We have a close relationship with the Galko lab using drosophila melanogaster models of pain to generate new hypotheses for pain mechanisms. We also collaborate with the Bedford group in Molecular Carcinogenesis to look at epigenetic mechanisms underlying chronic pain.
Donica, CL, Cui, Y, Shi, S, and Gutstein, HB: PDGFR-ß antagonism restores morphine analgesic efficacy against neuropathic pain, PLoS ONE 9(5): e97105. doi:10.1371/journal.pone.0097105, 2014
Wang, Y, Barker, KE, Shi, S, Diaz, MF, Mo, B, and Gutstein, HB: Blockade of morphine-induced PDGFR-? activation eliminates morphine analgesic tolerance, Nature Medicine, 18:385, 2012
Morris, JS, Baladandayuthapani, V, Herrick, RC, Sanna, PP, and Gutstein, H: Automated Analysis of Quantitative Image Data using Isomorphic Functional Mixed Models, with Application to Proteomics Data, The Annals of Applied Statistics, 5:894, 2011
Babcock, DT, Shi, S, Shaw. M, Gutstein, HB and Galko, MJ: Hedgehog signaling regulates nociceptive sensitization, Current Biology, 27:1525, 2011