The objective of this thesis was to elucidate the neurophysiological and neurochemical bases for modulation of sensory transmission in the spinal cord evoked by the activation of primary afferents in the lightly anaesthetized rat. Effects of prolonged, intense (20 $ times$ threshold), low frequency (4 Hz) stimulation of meridian and non-meridian sites on the thermally evoked nociceptive withdrawal reflexes of the tail and limbs were studied. Threshold was the minimum current required to elicite muscle contraction. / Intense stimulation applied to meridian sites inhibited tail withdrawal. This inhibition persisted beyond one hour after the end of stimulation. Stimulation of non-meridian sites produced a smaller inhibition; this occurred during the conditioning only. Thus, a brief inhibition or both the brief and a persistent, post-stimulation inhibition were produced by stimulation of non-meridian or meridian sites, respectively. Little effect was evoked on limb withdrawal reflexes. / Expression of the post-stimulation effect required 20 $ times$ threshold stimulation with long pulse durations ($ geq$2 ms), low frequency of stimulation (2 Hz-6 Hz) and long train durations (20 or 40 min). The brief effect could be evoked at 10 $ times$ threshold with short pulse durations($ leq$2 ms) at higher frequencies of stimulation (8 Hz) and with short train durations (10 min). / Stimulation of meridian sites evoked both the brief and the post-stimulation effects in chronic spinal transected rats (7-14 days): in acutely spinal transected rats ($ leq$48 h) the brief effect was evoked only. The return of the post-stimulation effect was coincident with the return of bladder function. / Both the brief and post-stimulation inhibition were blocked by the competitive NMDA receptor antagonist 5-amino-2-phosphonovaleric acid (APV). / The wide spectrum opiate receptor antagonist naloxone, or $ mu$-opiate antagonist $ beta$-funaltrexamine, attenuated both the brief and persistent inhibition. The $ delta$- and $ kappa$-antagonists, TIPP($ psi$) and nor-binaltorphimine, attenuated the inhibition during the stimulation. Both drugs blocked the post-stimulation effect and even facilitated withdrawal. In chronically spinal transected rats, naloxone blocked the inhibition. / These data suggest that intense, low frequency activation of primary afferents arising from meridian but not non-meridian sites produces both brief and persistent inhibition of the tail withdrawal reflex. Limb withdrawal reflexes are only minimally inhibited by this activation. It is suggested that the persistent antinociception may be due to long-term plastic changes in inhibitory mechanisms within the CNS because these effects persist long after the end of stimulation and presumably after synaptic inputs from these fibres have ceased. It is also suggested that inhibitory mechanisms are provoked by prolonged activation of high threshold fibres, are dependent on the parameters of stimulation, are extrasegmental in nature and differentially modulate tail vs. limb nociceptive reflexes. Activation of spinal NMDA receptors appears critical for the expression of the persistent antinociception. The inhibition is also differentially mediated by activation of multiple opiate receptors: $ mu$-, $ kappa$- and to a lesser degree $ delta$-receptors mediate the brief effect, while the persistent antinociception is dependent on activation of $ delta$ -and $ kappa$-receptors and to a lesser degree $ mu$-receptors. Data from spinal animals suggest that the mechanisms mediating the inhibitory effects include both spinal and supraspinal components.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.39986 |
| Date | January 1995 |
| Creators | Romita, Vito Vittorio |
| Contributors | Henry, James L. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Physiology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001480979, proquestno: NN12468, Theses scanned by UMI/ProQuest. |
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