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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
Open accessAbstract
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 co-morbidity (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.
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“Systemic WIN55,212-2, administered from days 18-21 post infection, fully reversed mechanical allodynia to baseline levels in this model of post herpetic neuralgia, although pharmacological specificity was not assessed.131”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [131]
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Metadata
- Authors
- Hasnie, F. S., Breuer, J., Parker, S., Wallace, V., Blackbeard, J., Lever, I., Kinchington, P. R., Dickenson, A. H., Pheby, T., & Rice, A. S. C.
- Affiliations
- Chelsea and Westminster Hospital (GB)
- Queen Mary University of London (GB)
- University of Pittsburgh (US)
- University College London (GB)
- Corresponding author
- Rice, A.S.C.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2007-02
- Volume
- 144
- Issue
- 4
- Pages
- 1495-1508
- ISSN
- 0306-4522 (ISSN-L)
- PMC
- PMC2394505
- OpenAlex
- W1987479668
- Cited by
- 144
- References
- 48
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 4 · 2023: 6 · 2022: 4 · 2021: 8 · 2020: 5 · 2019: 5 · 2018: 2 · 2017: 13 · 2016: 7 · 2015: 10 · 2014: 13 · 2013: 9 · 2012: 9
- FWCI
- 5.97
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust
- National Institutes of Health (5r01ey007397-14)
- National Eye Institute (EY-07397, EY08098, R01EY009397, P30EY008098)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Infectious Diseases › Herpesvirus Infections and Treatments
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Keywords
- varicella-zoster virus, herpes zoster pain, postherpetic neuralgia, mechanical hypersensitivity, anxiety-like behavior, analgesics, gabapentin, morphine, amitriptyline, ibuprofen, WIN 55,212-2, cannabinoid analgesia, acyclovir, peripheral nerve injury, virus strain comparison, dose-response relationship, rat model
- MeSH terms
- Gabapentin, Amines, Analgesics, Animals, Anxiety Disorders, Cells, Cultured, Cyclohexanecarboxylic Acids, Disease Models, Animal, Fibroblasts, gamma-Aminobutyric Acid, Hyperalgesia, Male, Motor Activity, Nociceptors, Pain Measurement, Peripheral Nerves, Physical Stimulation, Anti-Anxiety Agents, Herpesvirus 3, Human, Rats, Wistar, Pain Threshold, Viral Load, Rats, Neuralgia, Postherpetic
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