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Title: The role of N-methyl D-aspartate (NMDA) receptor antagonists in neuropathic pain
Author: Wilson, John A.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2008
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The aim of this thesis is to investigate the use of NMDAR antagonists in preventing naturopathic sensitisation. The chronic constriction injury (CCI) model of neuropathic pain is used to study the role of NMDARs in the development of neuropathic pain and subsequent modulation. Behavioural effects are assessed in association with changes in NMDAR subtypes. Memantine and ketamine (NMDAR antagonists) are shown to attenuate typical behavioural responses (thermal hyperalgesia and cold allodynia) to nerve injury. In addition, NMDAR antagonist pre-treatment is shown to effect the subsequent NMDAR subunit expression, with improved susceptibility to subsequent NMDAR antagonist treatment. The clinical use of epidural ketamine as a preventative drug prior to lower limb amputation is investigated in a double blind randomised placebo controlled study. No significant effects on the incidence of post-amputation pain were found, although the overall incidence of pain was lower than in comparable studies. Ketamine is shown to improve peri-operative analgesia and have long lasting effects (up to one week) on sensory processing in the remaining stump. In summary, NMDAR antagonists seem to be effective in attenuating neuropathic pain in animal models. The promise shown in these studies has not translated into a reduction in post-amputation pain in a clinical study. Ketamine remains a clinically useful drug in peri-operative pain management but the role of ketamine and other clinically available NMDAR antagonists in the prevention of neutropathic sensitisation is still not clearly defined.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available