Repeated morphine treatment-mediated hyperalgesia, allodynia and spinal glial activation are blocked by co-administration of a selective cannabinoid receptor type-2 agonist

J Neuroimmunol. 2012 Mar;244(1-2):23-31. doi: 10.1016/j.jneuroim.2011.12.021. Epub 2012 Jan 30.

Abstract

Spinal glial activation has been implicated in sustained morphine-mediated paradoxical pain sensitization. Since activation of glial CB2 cannabinoid receptors attenuates spinal glial activation in neuropathies, we hypothesized that CB2 agonists may also attenuate sustained morphine-mediated spinal glial activation and pain sensitization. Our data indicate that co-administration of a CB2-selective agonist (AM 1241) attenuates morphine (intraperitoneal; twice daily; 6 days)-mediated thermal hyperalgesia and tactile allodynia in rats. A CB2 (AM 630) but not a CB1 (AM 251) antagonist mitigated this effect. AM 1241 co-treatment also attenuated spinal astrocyte and microglial marker and pro-inflammatory mediator (IL-1β, TNFα) immunoreactivities in morphine-treated rats, suggesting that CB2 agonists may be useful to prevent the neuroinflammatory consequences of sustained morphine treatment.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Analgesics / administration & dosage*
  • Analgesics, Opioid / adverse effects*
  • Animals
  • Cannabinoids / administration & dosage
  • Hyperalgesia / chemically induced
  • Hyperalgesia / drug therapy*
  • Indoles / administration & dosage*
  • Inflammation / drug therapy
  • Interleukin-1beta / analysis
  • Male
  • Morphine / adverse effects*
  • Neuroglia / drug effects*
  • Neuroglia / physiology
  • Pain / chemically induced
  • Pain / drug therapy
  • Piperidines / administration & dosage
  • Pyrazoles / administration & dosage
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Cannabinoid, CB2 / agonists*
  • Spinal Cord / cytology
  • Spinal Cord / drug effects*
  • Spinal Cord / physiology
  • Tumor Necrosis Factor-alpha / analysis

Substances

  • AM 1241
  • Analgesics
  • Analgesics, Opioid
  • Cannabinoids
  • Indoles
  • Interleukin-1beta
  • Piperidines
  • Pyrazoles
  • Receptor, Cannabinoid, CB2
  • Tumor Necrosis Factor-alpha
  • AM 251
  • Morphine
  • iodopravadoline