Constitutive μ-opioid receptor activity leads to long-term endogenous analgesia and dependence

G. Corder, S. Doolen, R. R. Donahue, M. K. Winter, B. L. Jutras, Y. He, X. Hu, J. S. Wieskopf, J. S. Mogil, D. R. Storm, Z. J. Wang, K. E. McCarson, B. K. Taylor

Research output: Contribution to journalArticle

108 Scopus citations

Abstract

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 μ-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 MOR CA suppression of withdrawal hyperalgesia may prevent the transition from acute to chronic pain.

Original languageEnglish (US)
Pages (from-to)1394-1399
Number of pages6
JournalScience
Volume341
Issue number6152
DOIs
StatePublished - Jan 1 2013

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    Corder, G., Doolen, S., Donahue, R. R., Winter, M. K., Jutras, B. L., He, Y., Hu, X., Wieskopf, J. S., Mogil, J. S., Storm, D. R., Wang, Z. J., McCarson, K. E., & Taylor, B. K. (2013). Constitutive μ-opioid receptor activity leads to long-term endogenous analgesia and dependence. Science, 341(6152), 1394-1399. https://doi.org/10.1126/science.1239403