Behavioural Co-morbidities in Rat Models of Neuropathic Pain
Author(s)
Legg, Ewen
Type
Thesis
Abstract
Pain is a complex experience involving both sensory and emotional aspects. Neuropathic pain
syndromes, which remain a major area of unmet clinical need, are often associated with
behavioural co-morbidities such as anxiety and depression. Recent studies have demonstrated
changes in a number of affect-related outcome measures in rodent models of neuropathic pain.
The expansion of such outcome measures offers one possible route for the improvement of
studies aimed at creating novel therapies for neuropathic pain.
Bias reduction through randomisation requires mixed housing of animals with peripheral nerve
injuries with non-injured conspecifics. Such mixed housing was shown to alter behaviour in the
open field. Therefore, in the following studies treatments were allocated to cage groups as a
whole. Anxiety-like behaviour was demonstrated in L5 spinal nerve transected (L5 SNT) rats in a
novel dark/light preference test and the utility of this test in detecting efficacious analgesics was
investigated. The possible presence of neuropathy-induced depression-like behaviour following
L5 SNT was then investigated using the forced swim test. However, animals showed no increase
in depression-like behaviour, as measured by time spent immobile in the forced swim test, at
either two or three weeks post-neuropathy. Assessment of burrowing behaviour, a novel
behavioural outcome measure thought to reflect over all well being in rodents, was then carried
out in rats following L5 SNT and partial sciatic nerve ligation. A reduction in burrowing
behaviour was demonstrated in both models of neuropathic pain compared to naive animals.
The use of novel outcome measures, such as those detailed above, both as outcome measures in
drug development and in studies into pathophysiology will improve the quality of studies aimed
at creating novel therapies for neuropathic pain.
syndromes, which remain a major area of unmet clinical need, are often associated with
behavioural co-morbidities such as anxiety and depression. Recent studies have demonstrated
changes in a number of affect-related outcome measures in rodent models of neuropathic pain.
The expansion of such outcome measures offers one possible route for the improvement of
studies aimed at creating novel therapies for neuropathic pain.
Bias reduction through randomisation requires mixed housing of animals with peripheral nerve
injuries with non-injured conspecifics. Such mixed housing was shown to alter behaviour in the
open field. Therefore, in the following studies treatments were allocated to cage groups as a
whole. Anxiety-like behaviour was demonstrated in L5 spinal nerve transected (L5 SNT) rats in a
novel dark/light preference test and the utility of this test in detecting efficacious analgesics was
investigated. The possible presence of neuropathy-induced depression-like behaviour following
L5 SNT was then investigated using the forced swim test. However, animals showed no increase
in depression-like behaviour, as measured by time spent immobile in the forced swim test, at
either two or three weeks post-neuropathy. Assessment of burrowing behaviour, a novel
behavioural outcome measure thought to reflect over all well being in rodents, was then carried
out in rats following L5 SNT and partial sciatic nerve ligation. A reduction in burrowing
behaviour was demonstrated in both models of neuropathic pain compared to naive animals.
The use of novel outcome measures, such as those detailed above, both as outcome measures in
drug development and in studies into pathophysiology will improve the quality of studies aimed
at creating novel therapies for neuropathic pain.
Date Issued
2011
Date Awarded
2011-11
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Rice, Andrew
Creator
Legg, Ewen
Publisher Department
Medicine: Department of Surgery and Cancer
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)