Opioid-induced redistribution of 6TM and 7TM μ opioid receptors: A hypothesized mechanistic facilitator model of opioid-induced hyperalgesia.
Opioids are still the most popular form of pain treatment, but many unavoidable side effects make opioids a big challenge in effective pain management. Opioid-induced hyperalgesia (OIH), a paradoxical phenomenon, portrays an increased sensitivity to harmful stimuli caused by opioid exposure. Changes in the neural modulation are considered a major contributor to the development of OIH. Activation of opioid receptors (ORs) and corresponding downstream molecules are the vital composition of functional performance of opioids. Increasing interests were proposed of the interaction between ORs and other neural transmitter systems such as glutamatergic, GABAergic and adrenergic ones to the genesis of OIH. G protein coupled μ-opioid receptor (MOR) was studied comprehensively on its role in the development of OIH. In addition to the relationship between MOR and other neurotransmitter receptors, a new intracellular MOR that has six transmembrane (6TM) domains was identified, and found to perform a pro-nociceptive task in contrast to the counterpart 7TM isoform. A mechanistic model of OIH in which both 6TM and 7TM MORs undergoing membrane redistribution upon opioid exposure is proposed which eventually facilitates the neurons more sensitive to nociceptive stimulation than that of the preceding opioid exposure.
Department of Anesthesiology, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China.
Wei
W
Wang
Department of Anesthesiology, Affiliated Chaohu Hospital, Anhui Medical University, Chaohu, Anhui, China.
Yan
Y
Wang
Department of Anesthesiology, Nanjing T.C.M. Hospital, Nanjing, China.
Wei
W
Zhang
The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China.
Xiaoju
X
Jin
Department of Anesthesiology, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China.
Yusheng
Y
Liu
Department of Anesthesiology, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China.
Shiqin
S
Xu
Department of Anesthesiology, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China.
Liming
L
Lei
Department of Anesthesiology, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China.
Xiaofeng
X
Shen
Pediatric Institute, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China.
Xirong
X
Guo
Department of Anesthesiology, Affiliated Chaohu Hospital, Anhui Medical University, Chaohu, Anhui, China. Electronic address: 2366833@sina.com.
Xiaoqiong
X
Xia
Department of Anesthesiology, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China; Division of Neuroscience, The Bonoi Academy of Science and Education, Chapel Hill, NC, USA. Electronic address: zfwang50@njmu.edu.cn.
Fuzhou
F
Wang
D000701:Analgesics, Opioid / Q000494:pharmacology*; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000187:drug effects* / Q000378:metabolism*
D000701:Analgesics, Opioid; D020033:Protein Isoforms; D017450:Receptors, Opioid, mu
G-protein coupled receptor; Hyperalgesia; Opioids; Receptor redistribution; μ-opioid receptor