Morphine currently represents the best option for the management of severe pain and chronic pain states. Prolonged use of opiates often produces the need for ever- increasing doses to maintain pain relief, also known as analgesic tolerance. The mechanisms associated with analgesic tolerance are thought to due to morphine- induced cellular adaptations that produce a state of heightened pain or hyperalgesia. Recent studies suggest that opiates acting via the mu-opioid receptor can induce expression of chemokines and their receptors. Previous works from our laboratory demonstrate that some of these same chemokines/receptors have been shown to play central roles in chronic pain states. To uncover evidence of possible links between chronic morophine treatment, chemokine signaling and analgesic tolerance, we propose the hypothesis that opiate-induced chemokine signaling is central to analgesic tolerance.
Our specific aims i nclude 1) a characterization of the chronology of cellular/signaling events associated with opiate-induced hyperalgesia 2) explore mechanisms by which morphine induces chemokine/receptor expression in the dorsal root ganglia and 3) examine the cellular/molecular mechanisms by which chronic morphine treatment enhances chemokine signaling. Better understanding of these chemokine/receptor- mediated events may provide the necessary framework for the design of agents that counteract deleterious opiate-induced cellular adaptations and effectively reduce analgesic tolerance.
Morphine is a powerful pain reliever for cancer and non-cancer pain, but also a potent inducer of tolerance. Opiate tolerance refers to a phenomenon in which exposure to a opiate results in the diminution of an analgesic effect (pain relief). Tolerance to the analgesic effect of morphine is a poorly understood phenomenon and can clearly present major management difficulties in some patients. Better understanding of the events associated with the development of tolerance may provide the necessary framework for the design of agents effectively reduce analgesic tolerance.
|Due, Michael R; Yang, Xiao-Fang; Allette, Yohance M et al. (2014) Carbamazepine potentiates the effectiveness of morphine in a rodent model of neuropathic pain. PLoS One 9:e107399|
|Due, Michael R; Park, Jonghyuck; Zheng, Lingxing et al. (2014) Acrolein involvement in sensory and behavioral hypersensitivity following spinal cord injury in the rat. J Neurochem 128:776-86|
|Allette, Yohance M; Due, Michael R; Wilson, Sarah M et al. (2014) Identification of a functional interaction of HMGB1 with Receptor for Advanced Glycation End-products in a model of neuropathic pain. Brain Behav Immun 42:169-77|
|Ju, Weina; Li, Qi; Allette, Yohance M et al. (2013) Suppression of pain-related behavior in two distinct rodent models of peripheral neuropathy by a homopolyarginine-conjugated CRMP2 peptide. J Neurochem 124:869-79|
|Wang, Yuying; Khanna, Rajesh (2011) VOLTAGE-GATED CALCIUM CHANNELS ARE NOT AFFECTED BY THE NOVEL ANTI-EPILEPTIC DRUG LACOSAMIDE. Transl Neurosci 2:13-22|
|Brittain, Joel M; Duarte, Djane B; Wilson, Sarah M et al. (2011) Suppression of inflammatory and neuropathic pain by uncoupling CRMP-2 from the presynaptic Ca²? channel complex. Nat Med 17:822-9|
|Wilson, Natalie M; Jung, Hosung; Ripsch, Matthew S et al. (2011) CXCR4 signaling mediates morphine-induced tactile hyperalgesia. Brain Behav Immun 25:565-73|
|Wyatt, Debra; Malik, Rohit; Vesecky, Alissa C et al. (2011) Small ubiquitin-like modifier modification of arrestin-3 regulates receptor trafficking. J Biol Chem 286:3884-93|
|Foster, R; Jung, J; Farooq, A et al. (2011) Sciatic nerve injury induces functional pro-nociceptive chemokine receptors in bladder-associated primary afferent neurons in the rat. Neuroscience 183:230-7|
|Caballero, Adriana; Marchese, Adriano (2011) Ubiquitination of GPCRs. Methods Mol Biol 746:251-9|
Showing the most recent 10 out of 22 publications