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Supplemental Data for Science 2013 Corder et al. Constitutive mu-opioid receptor activity leads to long-term endogenous analgesia and dependence
(2013)
  • Renee R. Donahue, University of Kentucky
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 m-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.

Keywords
  • mu opioid receptor,
  • hyperalgesia,
  • allodynia,
  • CFA,
  • naltrexone,
  • latent sensitization,
  • NB001,
  • cAMP,
  • 6B naltrexol,
  • post-surgical pain,
  • forskolin,
  • NMDA
Publication Date
2013
Citation Information
Renee R. Donahue. "Supplemental Data for Science 2013 Corder et al. Constitutive mu-opioid receptor activity leads to long-term endogenous analgesia and dependence" (2013)
Available at: http://works.bepress.com/renee_donahue/10/