Constitutive μ-Opioid Receptor Activity Leads to Long-Term Endogenous Analgesia and Dependence

被引：198

作者：

Corder, G. ^{[1
]}

Doolen, S. ^{[1
]}

Donahue, R. R. ^{[1
]}

Winter, M. K. ^{[2
]}

Jutras, B. L. ^{[3
]}

He, Y. ^{[4
]}

Hu, X. ^{[4
]}

Wieskopf, J. S. ^{[5
,6
]}

Mogil, J. S. ^{[5
,6
]}

Storm, D. R. ^{[7
]}

Wang, Z. J. ^{[4
]}

McCarson, K. E. ^{[2
]}

Taylor, B. K. ^{[1
]}

机构：

[1] Univ Kentucky, Dept Physiol, Lexington, KY 40536 USA

[2] Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66160 USA

[3] Univ Kentucky, Dept Microbiol Immunol & Mol Genet, Lexington, KY 40536 USA

[4] Univ Illinois, Dept Biopharmaceut Sci, Chicago, IL 60612 USA

[5] McGill Univ, Dept Psychol, Montreal, PQ H3A 1B1, Canada

[6] McGill Univ, Alan Edwards Ctr Res Pain, Montreal, PQ H3A 1B1, Canada

[7] Univ Washington, Sch Med, Dept Pharmacol, Seattle, WA 98195 USA

来源：

SCIENCE | 2013年 / 341卷 / 6152期

关键词：

ADENYLYL-CYCLASE; CENTRAL SENSITIZATION; INFLAMMATORY PAIN; POTENTIATION; HYPERALGESIA; ACTIVATION; WITHDRAWAL; INCREASES; NALOXONE; PROTEIN;

D O I：

10.1126/science.1239403

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Opioid receptor antagonists increase hyperalgesia in humans and animals, which indicates that endogenous activation of opioid receptors provides relief from acute pain; however, the mechanisms of long-term opioid inhibition of pathological pain have remained elusive. We found that tissue injury produced mu-opioid receptor (MOR) constitutive activity (MORCA) that repressed spinal nociceptive signaling for months. Pharmacological blockade during the posthyperalgesia state with MOR inverse agonists reinstated central pain sensitization and precipitated hallmarks of opioid withdrawal (including adenosine 3',5'-monophosphate overshoot and hyperalgesia) that required N-methyl-D-aspartate receptor activation of adenylyl cyclase type 1. Thus, MORCA initiates both analgesic signaling and a compensatory opponent process that generates endogenous opioid dependence. Tonic MORCA suppression of withdrawal hyperalgesia may prevent the transition from acute to chronic pain.

引用

页码：1394 / 1399

页数：6

共 51 条

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