INTRAVENOUS ACETYLSALICYLIC-ACID INHIBITS CENTRAL TRIGEMINAL NEURONS IN THE DORSAL HORN OF THE UPPER CERVICAL SPINAL-CORD IN THE CAT

Acetylsalicylic acid (ASA) is one of the most commonly used substances in the treatment of headache and other pain syndromes. It is only recently that its efficacy in the treatment of acute attacks and in the prophylaxis of migraine has been proven in clinical trials. Various peripheral and central mechanisms have been proposed for the analgesic effects of acetylsalicylic acid and its mode of action in migraine. The possible actions of acetylsalicylic acid in migraine include local analgesic affects, changes in cerebral serotonin turnover, modulation of antinociceptive neurons in the hypothalamus and inhibition of the release of algogenic peptides during neurogenic inflammation. In this study trigeminal somatosensory evoked potentials and single unit activity of central trigeminal neurons in the dorsolateral C-2 spinal cord were monitored during electrical stimulation of the superior sagittal sinus in the cat. Intravenous administration of the soluble acetylsalicylic salt (acetylsalicylic lysinate, 30mg/kg) reduced the peak-to-peak amplitudes of somatosensory evoked potentials from 219 +/- 11mV by 18% after 45 minutes and by 26% after 60 minutes. Naloxone injection (0.5 mg/kg and 1.5 mg/kg) did not reverse the inhibition caused by ASA. The probability of trigeminal cell tiring was reduced in 63% percent of the monitored single units. The effect was not mediated through naloxone-sensitive opioid receptors and was independent from ASA-induced peripheral blockade of neuropeptides during neurogenic inflammation. The non-steroidal anti-inflammatory agent ketorolac (0.4mg/kg, IVI) a new cyclooxygenase inhibitor, also reduced the somatosensory evoked potentials by 30% following the same time course. The data suggest that ASA exerts inhibitory effects on central trigeminal neurons, possibly mediated through inhibition of prostaglandin synthesis and that these may be responsible for its effects in the treatment of migraine.