Local application of the cannabinoid receptor agonist, WIN 55,212-2, to spinal trigeminal nucleus caudalis differentially affects nociceptive and non-nociceptive neurons

Pain. 2004 Feb;107(3):267-275. doi: 10.1016/j.pain.2003.11.009.


Cannabinoid receptor agonists produce analgesia for pains of non-cranial origin. However, their effectiveness for craniofacial pains is currently unclear. In the present study, the cannabinoid CB1/CB2 receptor agonist, WIN 55,212-2 (WIN), was bath applied to the brainstem while activity of spinal trigeminal nucleus caudalis (Vc) neurons evoked by transcutaneous electrical stimulation was recorded in isoflurane anesthetized rats. Neurons were characterized using mechanical and electrical stimulation of the face, and were classified as either low-threshold mechanoreceptive (LTM) or wide dynamic range (WDR). LTM neurons responded to light brushing of the receptive field and received only Abeta primary afferent fiber input. WDR neurons showed a graded response to mechanical stimulation, responding maximally to noxious stimuli, and demonstrated both A- and C-fiber evoked activity. In addition, WDR neurons displayed longer latency, C-fiber mediated post-discharge (PDC) activity after repetitive stimulation. Local bath application of 2.0 mg/ml WIN significantly reduced PDC activity (3+/-1% control, P<0.01), C-fiber evoked activity (58+/-9% control, P<0.01), and Abeta evoked activity (57+/-10% control, P<0.01) in WDR neurons. In contrast, LTM Abeta-fiber evoked activity increased after local administration of WIN (204+/-52% control, P<0.01). SR141716A, a CB1 receptor antagonist, prevented the effects of WIN on WDR PDC and LTM Abeta evoked activity. These results indicate that cannabinoid receptor agonists may be effective agents for craniofacial pain. Furthermore, the particular sensitivity of PDC activity, a measure of neuronal hyperexcitability, to cannabinoid receptor agonists may be relevant to the treatment of persistent craniofacial pain.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / radiation effects
  • Analgesics / pharmacology*
  • Analgesics / therapeutic use
  • Analysis of Variance
  • Animals
  • Benzoxazines
  • Cannabinoid Receptor Agonists*
  • Electric Stimulation
  • Electrophysiology / methods
  • Facial Pain / drug therapy
  • Male
  • Morpholines / pharmacology*
  • Morpholines / therapeutic use
  • Naphthalenes / pharmacology*
  • Naphthalenes / therapeutic use
  • Neurons / classification
  • Neurons / drug effects*
  • Nociceptors / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cannabinoid / metabolism
  • Trigeminal Nerve / physiology
  • Trigeminal Nerve / radiation effects
  • Trigeminal Nucleus, Spinal / cytology*
  • Trigeminal Nucleus, Spinal / drug effects


  • Analgesics
  • Benzoxazines
  • Cannabinoid Receptor Agonists
  • Morpholines
  • Naphthalenes
  • Receptors, Cannabinoid
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone