BULBOSPINAL AND INTRASPINAL THYROTROPIN-RELEASING-HORMONE SYSTEMS - MODULATION OF SPINAL-CORD PAIN TRANSMISSION

Recent research indicates that pain processing by spinal nociceptive neurons is modulated by: 1) descending bulbospinal pathways originating in the rostral ventral medulla (RVM) and 2) short intraspinal peptide systems located in the dorsal horn. Immunohistochemical studies have identified both bulbospinal and intraspinal thyrotropin releasing hormone (TRH) systems, however, the role of these two TRH systems in pain modulation has not been defined. The purpose of the present study was to explore the role of the bulbospinal and intraspinal TRH systems in pain modulation. Three TRH mediated neural network were examined in electrophysiologic experiments; each model predicting specific testable outcomes. Model A represented a direct TRH projection from RVM to spinal cord. This model predicted that the effect of RVM stimulation and TRH micropressure administration on dorsal horn unit activity would be in the same direction, either both inhibitory effects or both excitatory. Of 44 dorsal horn units inhibited by RVM stimulation, 82% were excited by TRH, therefore, Model A was rejected. Model B interposed an intraspinal neuron between the bulbospinal TRH projection and the dorsal horn nociceptive unit. This model predicted that desensitization of spinal TRH receptor systems should block the effect of RVM stimulation on dorsal horn neuron. In TRH desenisitization experiments, no attenuation or blockade of RVM stimulation was observed, therefore, the effect of RVM stimulation did not appear mediated by TRH and Model B was rejected. Model C, which described an intraspinal TRH system facilitating pain transmission was supported by several lines of evidence including: 1) prominent increase in unit activity after TRH micropressure application and 2) the ability of TRH to magnify the effect of noxious stimulation on unit activity while having little or no effect on baseline firing rate. It is concluded that TRH interneurons may either directly or indirectly, via modulation of transmitter release from primary afferents, facilitate pain transmission in spinal cord while the modulation of pain transmission by the bulbospinal TRH system could not be clearly demonstrated under the present experimental conditions. © 1990.