The analgesic effects of R(+)-WIN 55,212-2 mesylate, a high affinity cannabinoid agonist, in a rat model of neuropathic pain

Neurosci Lett. 1997 Jan 17;221(2-3):157-60. doi: 10.1016/s0304-3940(96)13308-5.


The effects of a high affinity cannabinoid receptor agonist were evaluated in rats subjected to chronic constriction injury of the sciatic nerve (CCI) or a sham operation. Intraperitoneal (i.p.) injections of the active, but not the inactive enantiomer, alleviated the pain behavior exhibited by CCI animals in a dose dependent manner. Moreover, at doses ranging from 0.43 to 4.3 mg/kg effects on sensitivity to a heat stimulus were observed neither in the paw contralateral to the sciatic ligation, nor in animals subjected to sham surgery. Animals subjected to CCI and treated with 4.3 mg/kg exhibited hypoalgesia in the paw ipsilateral to the ligated sciatic, i.e. heat hypoalgesia was completely reversed. The hypoalgesia is presumed to be the results of unmasking of a sensory deficit reflecting the known loss of C and A delta with CCI. Although side effects were present in some CCI animals subjected to the high dose (4.3 mg/kg), a moderate dose (2.14 mg/kg) completely alleviated the thermal and mechanical hyperalgesia, and mechanical allodynia without side effects. In addition to identifying a potential drug treatment for painful neuropathy, this study suggests that changes in cannabinoid receptors occurs in nerve injured animals.

MeSH terms

  • Analgesics, Non-Narcotic / pharmacology*
  • Animals
  • Benzoxazines
  • Cannabinoids / agonists*
  • Cannabinoids / antagonists & inhibitors
  • Hot Temperature
  • Hyperalgesia / drug therapy
  • Hyperalgesia / physiopathology
  • Injections, Intraperitoneal
  • Male
  • Morpholines / pharmacology*
  • Naphthalenes / pharmacology*
  • Pain / drug therapy*
  • Pain / etiology
  • Peripheral Nervous System Diseases / complications*
  • Piperidines / pharmacology
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cannabinoid
  • Receptors, Drug / agonists
  • Receptors, Drug / antagonists & inhibitors
  • Rimonabant


  • Analgesics, Non-Narcotic
  • Benzoxazines
  • Cannabinoids
  • Morpholines
  • Naphthalenes
  • Piperidines
  • Pyrazoles
  • Receptors, Cannabinoid
  • Receptors, Drug
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
  • Rimonabant