Study on the mechanisms of oro-facial and temporomandibular joint neuropathic pain control in the central nervous system

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The oral nociceptive signal is primarily processed in the rostral TSN above the obex, the nucleus principalis (Vp), and the subnuclei oralis (SpVo) and interpolaris (SpVi), while secondarily processed in the subnucleus caudalis (SpVc). In contrast, the facial nociceptive signal is primarily processed in the SpVc. The neurons projecting to the thalamus are localized mostly in the Vp, moderately in the SpVi, modestly in the ventrolateral SpVo and.the SpVc. Orofacial sensory inputs are modulated in many different ways; i.e. by interneurons in the TSN proper, through reciprocal connection between TSN and rostral ventromedial medulla, and by cerebral cortex. A wide variety of neuroactive substances, including substance P,γ^- aminobutyric acid (GABA), serotonin and nitric oxide (NO) could be involved in these circuits' modulatory functions. We found NK-1-bearing neurons in the SpVc have pivotal role in sensory modality-and intensity-dependent nociceptive processing through GABAA receptors. The earliest expression of NO synthase (NOS) in the developing rat brain is observed in a discrete neuronal population in the SpVo at embryonic day 15. NOS expression in the SpVc is late at postnatal day 10. The neurons receiving intraoral signals are intimately related with the sensorimotor reflexive function through the SpVo. Better understanding of the trigeminal sensory system, which is different from the spinal system, will help to find potential therapeutic targets and render developing new analgesics for orofacial-specific pain with high efficacy and less side effects.