Depletion of substance P, neurokinin A and calcitonin gene-related peptidefrom the contralateral and ipsilateral caudal trigeminal nucleus followingunilateral electrical stimulation of the trigeminal ganglion; a possible neurophysiological and neuroanatomical link to generalized head pain

Primary trigeminal neurons of the trigeminal ganglion (TG) innervate major parts of the face and head, including the dura. Electrical stimulation of t he TG at specific parameters, can activate its nociceptive neurons and may serve as an experimental pain model. Markowitz [J. Neurosci. 7 (1987) 4129] reported that electrical stimulation of the trigeminal ganglion (TG) cause s extravasation of plasma proteins From venules of the trigeminally innerva ted domain possibly due to the release of vasoactive substances. Neurogenic inflammation (vasodilatation. plasma protein extravasation, release of vas oactive peptides) in dura may serve as one of the possible pathomechanisms underlying vascular head pain [Moskowitz, Ann. Neurol. 16 (1984) 157]. We p erformed a unilateral electrical stimulation (7.5 Hz, 5 ms. 0.8-1.4 mA for 5 min) of the TG in rat, to induce a neurogenic inflammation in the periphe ral trigeminal domain including the dura. looking for calcitonin gene relat ed peptide (CGRP), substance P (SP) and neurokinin A (NKA) immunoreactivity (IR) in the caudal trigeminal nucleus (CTN) into which massive central tri geminal processes terminate. Here, we show patchy depletion(s) of CGRP-. SP - and NKA-IRs ill the contralateral CTN of the rat in addition to their ips ilateral depletion. Such depletion is due to the release of these neuropept ides in the CTN leading to the activation of bilateral trigeminal nocicepti ve pathway. These data afford the possibility that under specific frequenci es (which may roughly correlate to the intensity of the painful stimulus) a nd/or specific intensities (may correlate to specific areas of the peripher al trigeminal domain) of stimulation. activation of one side of the TG may activate bilateral trigeminal nociceptive pathway leading to the perception of an ill localized/generalized pain or headache rather than a unilateral one. (C) 2001 Elsevier Science B.V. All rights reserved.