title: The mechanism of μ-opioid receptor (MOR)-TRPV1 crosstalk in TRPV1 activation involves morphine anti-nociception, tolerance and dependence.
abstract: Initiated by the activation of various nociceptors, pain is a reaction to specific stimulus modalities. The μ-opioid receptor (MOR) agonists, including morphine, remain the most potent analgesics to treat patients with moderate to severe pain. However, the utility of MOR agonists is limited by the adverse effects associated with the use of these drugs, including analgesic tolerance and physical dependence. A strong connection has been suggested between the expression of the transient receptor potential vanilloid type 1 (TRPV1) ion channel and the development of inflammatory hyperalgesia. TRPV1 is important for thermal nociception induction, and is mainly expressed on sensory neurons. Recent reports suggest that opioid or TRPV1 receptor agonist exposure has contrasting consequences for anti-nociception, tolerance and dependence. Chronic morphine exposure modulates TRPV1 activation and induces the anti-nociception effects of morphine. The regulation of many downstream targets of TRPV1 plays a critical role in this process, including calcitonin gene-related peptide (CGRP) and substance P (SP). Additional factors also include capsaicin treatment blocking the anti-nociception effects of morphine in rats, as well as opioid modulation of TRPV1 responses through the cAMP-dependent PKA pathway and MAPK signaling pathways. Here, we review new insights concerning the mechanism underlying MOR-TRPV1 crosstalk and signaling pathways and discuss the potential mechanisms of morphine-induced anti-nociception, tolerance and dependence associated with the TRPV1 signaling pathway and highlight how understanding these mechanisms might help find therapeutic targets for the treatment of morphine induced antinociception, tolerance and dependence.
authors.affiliation: a Department of Oncology ; Guang'anmen Hospital, China Academy of Chinese Medical Sciences ; Beijing , P. R. China.
authors.forename: Yanju
authors.initials: Y
authors.lastname: Bao
authors.affiliation: a Department of Oncology ; Guang'anmen Hospital, China Academy of Chinese Medical Sciences ; Beijing , P. R. China.|b Beijing University of Chinese Medicine ; Beijing , P. R. China.
authors.forename: Yebo
authors.initials: Y
authors.lastname: Gao
authors.affiliation: c Department of Nephrology ; Guang'anmen Hospital, China Academy of Chinese Medical Sciences ; Beijing , P. R. China.
authors.forename: Liping
authors.initials: L
authors.lastname: Yang
authors.affiliation: d Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences ; Beijing , P. R. China.
authors.forename: Xiangying
authors.initials: X
authors.lastname: Kong
authors.affiliation: e Department of Oncology ; Beijing Friendship Hospital, Capital Medical University ; Beijing , China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.affiliation: a Department of Oncology ; Guang'anmen Hospital, China Academy of Chinese Medical Sciences ; Beijing , P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hou
authors.affiliation: a Department of Oncology ; Guang'anmen Hospital, China Academy of Chinese Medical Sciences ; Beijing , P. R. China.
authors.forename: Baojin
authors.initials: B
authors.lastname: Hua
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000378:metabolism*; D059225:Nociception; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu; D050916:TRPV Cation Channels; D009020:Morphine
keywords: calcitonin gene-related peptide (CGRP); ion channel; opioid tolerance; substance P (SP); transient receptor potential vanilloid type 1 (TRPV1); μ opioid receptor (MOR)