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Published on: January 18, 2019
Contribution of spinal glutamatergic mechanisms in heterosegmental antinociception induced by noxious stimulation
Claudia H Tambeli1, Andrew Young, Jon D Levine
1Department of Oral and Maxillofacial Surgery, UCSF School of Dentistry, University of California, P.O. Box 0440, 707 Parnassuss Ave., San Francisco, CA 94143-0440, USA.
Abstract:
We evaluated the role of spinal glutamate and substance P receptors in noxious stimulus-induced antinociception (NSIA). NSIA was produced by subdermal capsaicin administration in the hind paw of the rat and measured as attenuation of the jaw-opening reflex. NSIA was completely blocked by spinal intrathecal administration of the selective NMDA receptor antagonist LY235959 as well as the mGluR5 antagonists MPEP and SIB-1757 and partially attenuated by the selective AMPA/kainate receptor antagonist NBQX; however, neither the mGluR1 receptor antagonist LY367385 nor the NK1 antagonist L-703,606 affected NSIA. These results suggest that NSIA depends on glutamate, released from the central terminals of the primary afferent nociceptors, acting primarily on NMDA and mGluR5 receptors. Although substance P is also known to be released by similar stimuli, NK1 receptors do not appear to play a role in NSIA. The implications of these findings in the context of a proposed spinal circuit that mediates NSIA are discussed.
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