Reeve, Alison Jane; (1997) Electrophysiological studies on the pharmacology of adenosine related to nociceptive processing in the rat spinal cord. Doctoral thesis (Ph.D), UCL (University College London).

Text Electrophysiological_studies_o (1).pdf Download (28MB)

Abstract

These in vivo electrophysiological experiments establish the role of the purine, adenosine, in spinal cord processing of sensory information. Activation of the A1-receptor, by various agonists, selectively attenuated high-threshold inputs, namely the C-fibre evoked responses, wind-up and post-discharge, whilst sparing the low-threshold (Aβ-fibre evoked) responses. The Aδ-fibre evoked responses showed concurrent facilitations over the same dose range and time-course. The A2a-receptor appeared not to be important in spinal cord sensory processing. In models of acute inflammation, activation of the A1-receptor was effective in controlling both the first and second phase of the formalin induced response and agonist actions showed no change in potency following carrageenan induced inflammation compared to normal animals. Protecting endogenously released adenosine, with two novel adenosine kinase inhibitors, demonstrated that adenosine is released at the spinal cord level during noxious stimulation and that this results in antinociception. The predominant inhibitory effects of protected adenosine were on the post-discharge and wind-up. Spinally protected adenosine inhibited both the first and the second phase of the formalin evoked response, predominantly attenuating the tonic second phase. The results with protected adenosine suggest that adenosine is released in response to, and predominantly controls NMDA-receptor mediated events. After carrageenan induced inflammation, there was no change in the antinociception produced by the intrathecal kinase inhibitor compared to normal animals. However, when adenosine was protected by a kinase inhibitor given by the systemic route there was a marked increase in antinociception, suggesting an additional non-spinal site of antinociception after carrageenan. A1-receptor activation was effective in controlling bicuculline induced changes in neuronal responses, a model for certain neuropathic symptoms. These results extend our knowledge of the role of adenosine as a neuromodulator of spinal somatosensory processing, particularly nociception.

Download activity - last month

Export as JSONCSVXML

Download activity - last 12 months

Export as CSVXMLJSON

Downloads by country - last 12 months

Export as JSONCSVXML

Archive Staff Only

View Item