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Further characterization of a rat model of varicella zoster virus-associated pain: Relationship between mechanical hypersensitivity and anxiety-related behavior, and the influence of analgesic drugs

Hasnie, FS; Breuer, J; Parker, S; Wallace, V; Blackbeard, J; Lever, I; Kinchington, PR; ... Rice, ASC; + view all (2007) Further characterization of a rat model of varicella zoster virus-associated pain: Relationship between mechanical hypersensitivity and anxiety-related behavior, and the influence of analgesic drugs. NEUROSCIENCE , 144 (4) 1495 - 1508. 10.1016/j.neuroscience.2006.11.029.

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Abstract

Persistent herpes zoster-associated pain is a significant clinical problem and an area of largely unmet therapeutic need. Progress in elucidating the underlying pathophysiology of zoster-associated pain and related co-morbidity behavior, in addition to appropriately targeted drug development has been hindered by the lack of an appropriate animal model. This study further characterizes a recently developed rat model of zoster-associated hypersensitivity and investigates (a) response to different viral strains; (b) relationship between viral inoculum concentration ('dose') and mechanical hypersensitivity ('response'); (c) attenuation of virus-associated mechanical hypersensitivity by clinically useful analgesic drugs; and (d) measurement of pain comorbidity (anxiety-like behavior) and pharmacological intervention in the open field paradigm (in parallel with models of traumatic peripheral nerve injury). Varicella zoster virus was propagated on fibroblast cells before s.c. injection into the glabrous footpad of the left hind limb of adult male Wistar rats. Control animals received injection of uninfected fibroblast cells. Hind-limb reflex withdrawal thresholds to mechanical, noxious thermal and cooling stimuli were recorded at specified intervals post-infection. Infection with all viral strains was associated with a dose-dependent mechanical hypersensitivity but not a thermal or cool hypersensitivity. Systemic treatment with i.p. morphine (2.5 mg/kg), amitriptyline (10 mg/kg), gabapentin (30 mg/kg), (S)-(+)-ibuprofen (20 mg/kg) and the cannabinoid WIN55,212-2 (2 mg/kg) but not the antiviral, acyclovir (50 mg/kg), was associated with a reversal of mechanical paw withdrawal thresholds. In the open field paradigm, virus-infected and nerve-injured animals demonstrated an anxiety-like pattern of ambulation (reduced entry into the central area of the open arena) which was positively correlated with mechanical hypersensitivity. This may reflect pain-related co-morbidity. Further, anxiety-like behavior was attenuated by acute i.p. administration of gabapentin (30 mg/kg) in nerve-injured, but not virus-infected animals. This model will prove useful in elucidating the pathophysiology of zoster-associated pain and provide a tool for pre-clinical screening of analgesic drugs. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.

Type: Article
Title: Further characterization of a rat model of varicella zoster virus-associated pain: Relationship between mechanical hypersensitivity and anxiety-related behavior, and the influence of analgesic drugs
DOI: 10.1016/j.neuroscience.2006.11.029
Keywords: zoster-associated pain, postherpetic neuralgia, neuropathy, analgesia, open field, anxiety-like behavior, SPINAL NERVE LIGATION, DORSAL-ROOT GANGLIA, POSTHERPETIC NEURALGIA, NEUROPATHIC PAIN, PERIPHERAL NEUROPATHY, HERPES-ZOSTER, ALLODYNIA, GABAPENTIN, ACYCLOVIR, INFECTION
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: http://discovery.ucl.ac.uk/id/eprint/168099
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