The opioid placebo analgesia is mediated exclusively through μ-opioid receptor in rat

Rui-Rui Zhang1, Wen-Cai Zhang, Jin-Yan Wang

  • 1Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, PR China.

Insights

Placebo analgesia in rats involves the rostral anterior cingulate cortex (rACC). This pain relief is mediated exclusively by the mu-opioid receptor, not delta or kappa opioid receptors.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Pain Research

Background:

  • Placebo analgesia is a well-documented phenomenon.
  • Existing research implicates mu-opioid receptor signaling in human placebo analgesia.
  • The involvement of other opioid receptors in placebo analgesia remains largely unexplored.

Purpose of the Study:

  • To investigate the brain region responsible for placebo analgesia.
  • To determine which types of opioid receptors mediate placebo analgesia.
  • To establish and utilize a rat model for studying placebo analgesia.

Main Methods:

  • Established a placebo analgesia model in male Sprague-Dawley rats using morphine training.
  • Administered naloxone to block placebo analgesia, including via microinjection into the rostral anterior cingulate cortex (rACC).
  • Tested the effects of selective opioid receptor antagonists (CTOP for μ, NTI for δ, nor-BNI for κ) microinjected into the rACC.

Main Results:

  • Placebo analgesia in rats was blocked by naloxone, particularly when microinjected into the rACC.
  • Microinjection of CTOP (a μ-opioid receptor antagonist) into the rACC reduced the pain threshold in placebo analgesia rats.
  • NTI (δ-opioid receptor antagonist) and nor-BNI (κ-opioid receptor antagonist) did not affect placebo analgesia when administered into the rACC.

Conclusions:

  • The rostral anterior cingulate cortex (rACC) is a critical brain region for placebo analgesia.
  • Opioid-mediated placebo analgesia in rats is exclusively dependent on the μ-opioid receptor.
  • These findings provide insights into the neurobiological mechanisms of placebo effects.

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