title: Spinal TRPC6 channels contributes to morphine-induced antinociceptive tolerance and hyperalgesia in rats.
abstract: The chronic administration of opioids results in the development of morphine analgesic tolerance and withdrawl-induced hyperalgesia, which limits their clinical utility in pain treatment. However, the cellular mechanisms underlying opioid-induced tolerance and hyperalgesia are not fully understood. The transient receptor potential canonical channel TRPC6 is important for brain development and function, as it regulates cytosolic, endoplasmic reticulum, and mitochondrial Ca2+levels in neural cells. Here, we report that TRPC6 expression in the spinal cord was up-regulated after chronic morphine treatment. Furthermore, inhibition of TRPC6 in the spinal cord blocked the induction of morphine tolerance and hyperalgesia without affecting basal pain perception. These effects were attributed to the attenuation of morphine-induced neuroimmune activation and increased levels of CaMKIIα and nNOS in the spinal cord. This data suggests that specific TRPC6 inhibitors could be utilized for the prevention of morphine-induced antinociceptive tolerance and hyperalgesia in chronic pain management.
authors.affiliation: Department of Anesthesiology, Kunhua Hospital, The First People's Hospital of Yunnan Province, Kunming 650032, China. Electronic address: jinghuakm@163.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Jin
authors.affiliation: Medical Faculty, Kunming University of Science and Technology, Kunming 650500, China.
authors.forename: Ying-Tong
authors.initials: YT
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology, Kunhua Hospital, The First People's Hospital of Yunnan Province, Kunming 650032, China.
authors.forename: Guang-Qiong
authors.initials: GQ
authors.lastname: Guo
authors.affiliation: Department of Anesthesiology, Kunhua Hospital, The First People's Hospital of Yunnan Province, Kunming 650032, China.
authors.forename: Da-Lin
authors.initials: DL
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Kunhua Hospital, The First People's Hospital of Yunnan Province, Kunming 650032, China.
authors.forename: Yu-Jin
authors.initials: YJ
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Kunhua Hospital, The First People's Hospital of Yunnan Province, Kunming 650032, China.
authors.forename: Gao-Peng
authors.initials: GP
authors.lastname: Xiao
authors.affiliation: Department of Anesthesiology, Kunhua Hospital, The First People's Hospital of Yunnan Province, Kunming 650032, China.
authors.forename: Xin-Nan
authors.initials: XN
authors.lastname: Li
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D004361:Drug Tolerance / Q000502:physiology; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010146:Pain / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D050052:TRPC Cation Channels / Q000378:metabolism*
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D050052:TRPC Cation Channels; C492145:Trpc6 protein, rat; D009020:Morphine
keywords: Hyperalgesia; Morphine; TRPC6; Tolerance