Role of μ-opioid receptors in formalin-induced pain behavior in mice

Cheng Shui Zhao, Yuan Xiang Tao, Jill M. Tall, David M. Donovan, Richard A. Meyer, Srinivasa N. Raja

Research output: Contribution to journalArticlepeer-review

Abstract

Intraplantar formalin injection is widely used as an experimental model of tonic pain. We investigated the role of endogenous μ-opioid receptor mechanisms in formalin-induced nocifensive behavior in mice. The flinching response induced by formalin (2%, 20 μl) was studied in mice with normal (wild type, n = 8) and absent (homozygous μ-opioid receptor knockout, n = 8) μ-opioid receptor levels. The flinch responses were counted every 5 min for 60 min post-formalin injection. Lumbar spinal cord (L4, 5) was harvested 2 h post-formalin injection to examine c-Fos expression using immunohistochemistry. The effects of naloxone (5 mg/kg, sc) administered 30 min before the intraplantar formalin injection on the flinching response of wild-type mice (n = 7) were also recorded. The second-phase formalin response (10-60 min after formalin) was higher in homozygous μ-opioid receptor knockout mice compared to the wild-type mice (P < 0.01). Naloxone administration in wild-type mice before formalin injection resulted in pain behavior similar to that observed in homozygous μ-opioid receptor knockout mice (P > 0.05). The c-Fos expression induced by formalin injection in the knockout mice was not different from that observed in wild-type mice. Our results suggest that the endogenous μ-opioid system is activated by intraplantar formalin injection and exerts a tonic inhibitory effect on the pain behavior. These results suggest an important modulatory role of endogenous μ-opioid receptor mechanisms in tonic pain states.

Original languageEnglish (US)
Pages (from-to)839-845
Number of pages7
JournalExperimental Neurology
Volume184
Issue number2
DOIs
StatePublished - Dec 2003
Externally publishedYes

Keywords

  • Formalin test
  • Knockout
  • Naloxone
  • Opioid receptors
  • c-fos

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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