QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.106.106971v1 320/1/64    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Akerman, S. Articles by Goadsby, P. J. Search for Related Content PubMed PubMed Citation Articles by Akerman, S. Articles by Goadsby, P. J.

NEUROPHARMACOLOGY

Cannabinoid (CB₁) Receptor Activation Inhibits Trigeminovascular Neurons

Headache Group, Institute of Neurology and the National Hospital for Neurology and Neurosurgery, Queen Square, London, United Kingdom

Migraine is a common and disabling neurological disorder that involves activation or the perception of activation of the trigeminovascular system. Cannabinoid (CB) receptors are present in brain and have been suggested to be antinociceptive. Here we determined the effect of cannabinoid receptor activation on neurons with trigeminovascular nociceptive input in the rat. Neurons in the trigeminocervical complex (TCC) were studied using extracellular electrophysiological techniques. Responses to both dural electrical stimulation and cutaneous facial receptive field activation of the ophthalmic division of the trigeminal nerve and the effect of cannabinoid agonists and antagonists were studied. Nonselective CB receptor activation with R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2, 3-de]-1,4-benzoxazin-yl]-(1-naphthalenyl) (WIN55,212; 1 mg kg^–1) inhibited neuronal responses to A-(by 52%) and C-fiber (by 44%) afferents, an effect blocked by the CB₁ receptor antagonist SR141716 [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide; 3 mg kg^–1] but not the CB₂ receptor antagonist AM630 (6-iodopravadoline; 3 mg kg^–1). Anandamide (10 mg kg^–1) was able to inhibit both A- and C-fiber-elicited TCC firing, only after transient receptor potential vanilloid 1 receptor inhibition. Activation of cannabinoid receptors had no effect on cutaneous receptive fields when recorded from TCC neurons. The data show that manipulation of CB₁ receptors can affect the responses of trigeminal neurons with A- and C-fiber inputs from the dura mater. This may be a direct effect on neurons in the TCC itself or an effect in discrete areas of the brain that innervate these neurons. The data suggest that CB receptors may have therapeutic potential in migraine, cluster headache, or other primary headaches, although the potential hazards of psychoactive side effects that accompany cannabinoid treatments may be complex to overcome.

Address correspondence to: Professor Peter James Goadsby, Institute of Neurology, Queen Square, London WC1N 3BG, UK. E-mail: peterg{at}ion.ucl.ac.uk