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Pharmacological modulation of spinal somatosensory processing following peripheral nerve injury in the rat.

Suzuki, Rie; (2000) Pharmacological modulation of spinal somatosensory processing following peripheral nerve injury in the rat. Doctoral thesis (Ph.D), University College London. Green open access

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Chronic neuropathic pain state which arises from injury to the nervous system remains a significant problem. There have been few studies on the electrophysiological changes which take place in the spinal cord following peripheral nerve injury. I employed in vivo electrophysiological techniques to investigate the effect of nerve injury on the responses of spinal dorsal horn neurones in a rat model of neuropathy (Kim and Chung 1992). Following surgery for spinal nerve ligation, behavioural tests were carried out postoperatively in spinal nerve ligated (SNL) and sham operated rats. SNL rats displayed signs of mechanical and cold allodynia on the ipsilateral hindpaw which was maintained for 2 weeks. Sham operated rats displayed no changes in mechanical / cooling sensitivity on either hindpaw. Electrophysiological studies were conducted at PO 1 or 2 weeks (Dickenson and Sullivan 1986) and extracellular recordings of dorsal horn neurones were made under halothane anesthesia to characterise the responses of spinal neurones to electrical and natural stimuli. Following nerve injury, the C-fibre and mechanical evoked responses (von Frey filaments, prod) were significantly reduced compared to sham controls. In contrast, the acetone-evoked response and the receptive field size of spinal neurones to low-intensity mechanical stimuli were significantly increased in SNL rats. Additionally, a greater proportion of neurons exhibited high levels of spontaneous activities in SNL rats. Another objective was to study the effect of neuropathy on several pharmacological systems (opioid, N-methyl-D-aspartate and adenosine) through the use of selective agonists or antagonists. Overall, NMDA antagonists (ketamine, MK-801, memantine) produced greater inhibitions of the neuronal responses (wind-up, postdischarge, mechanical and thermal evoked responses) in SNL rats. Similarly, the adenosine agonist (CPA) and the adenosine kinase inhibitor (A200702.21) reduced the neuronal responses in both animal groups (input, wind-up, C-fibre and natural evoked responses). In sham operated rats, however, CPA produced a marked facilitation of the A?-fibre evoked response, however, this was absent after nerve injury. Interestingly, intrathecal morphine produced strong inhibitions of the neuronal responses and the reductions tended to be greater as compared to sham operated or naive rats. Systemic morphine produced smaller reductions of the neuronal responses as compared to the intrathecal route. The altered somatosensory processing of the pain transmitter systems may reflect the spinal neuronal plasticity which takes place following nerve injury. Agents which target these systems may prove to be have possible therapeutic roles for the treatment of neuropathic pain states.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Pharmacological modulation of spinal somatosensory processing following peripheral nerve injury in the rat.
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis Digitised by Proquest.
URI: https://discovery.ucl.ac.uk/id/eprint/10120938
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