Received for publication May 1, 2006.
Revised October 2, 2006.
Accepted for publication October 2, 2006.

Cannabinoid (CB1) receptor activation inhibits trigeminovascular neurons

Abstract

Migraine is a common and disabling neurological disorder that involves activation, or the perception of activation, of the trigeminovascular system. Cannabinoid receptors are present in brain and have been suggested to have an anti-nociceptive role. Here we determine the effect of cannabinoid receptor activation on neurons with trigeminovascular nociceptive input in the rat. Neurons in the trigeminocervical complex - trigeminal nucleus caudalis (TNC) and dorsal horn of the C1 region- 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. Non-selective CB receptor activation, with WIN55,212 (1 mgkg^-1, i.v) inhibited neuronal responses to A- (by 52%)and C-fiber (by 44 %) afferents, an effect that was blocked by the CB₁ receptor antagonist, SR141716 (3 mgkg^-1, i.v), but not the CB₂ receptor antagonist, AM630 (3 mgkg^-1, i.v). Anandamide (10 mgkg^-1, i.v) was also able to inhibit both A- and C-fiber elicited trigeminocervical complex (TCC) firing, but only after TRPV1 receptor inhibition. Activation of cannabinoid receptors had no effect on cutaneous receptive fields when recording 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 trigeminocervical complex 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.

Key words: WIN55,212, anandamide, cannabinoid, dura mater, migraine, trigeminocervical complex