Journal ArticleDOI
Establishment and characterisation of a stavudine (d4T)-induced rat model of antiretroviral toxic neuropathy (ATN) using behavioural and pharmacological methods
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TLDR
The rat model of ATN is suitable for investigation of the pathophysiology of d4T-induced SN as well as for profiling novel molecules from analgesic drug discovery programs.Abstract:
Human immuno-deficiency virus (HIV) associated sensory neuropathy (SN) is a frequent complication of HIV infection. It is extremely difficult to alleviate and hence the quality of life of affected individuals is severely and adversely impacted. Stavudine (d4T) is an antiretroviral drug that was widely used globally prior to 2010 and that is still used today in resource-limited settings. Its low cost and relatively good efficacy when included in antiretroviral dosing regimens means that there is a large population of patients with d4T-induced antiretroviral toxic neuropathy (ATN). As there are no FDA approved drugs for alleviating ATN, it is important to establish rodent models to probe the pathobiology and to identify potentially efficacious new drug treatments. In the model establishment phase, d4T administered intravenously at a cumulative dose of 375 mg/kg in male Wistar Han rats evoked temporal development of sustained mechanical allodynia in the hindpaws from day 10 to day 30 after initiation of d4T treatment. As this d4T dosing regimen was also well tolerated, it was used for ATN model induction for subsequent pharmacological profiling. Both gabapentin at 30–100 mg/kg and morphine at 0.3–2 mg/kg given subcutaneously produced dose-dependent relief of mechanical allodynia with estimated ED50’s of 19 mg/kg and 0.4 mg/kg, respectively. In contrast, intraperitoneal administration of meloxicam or amitriptyline up to 30 mg/kg and 7 mg/kg, respectively, lacked efficacy. Our rat model of ATN is suitable for investigation of the pathophysiology of d4T-induced SN as well as for profiling novel molecules from analgesic drug discovery programs.read more
Citations
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Journal ArticleDOI
Characterization of a mouse neuropathic pain model caused by the highly active antiviral therapy (HAART) Stavudine.
Jenny L. Wilkerson,Jasmine S. Felix,Joshua A. Bilbrey,Christopher R. McCurdy,Lance R. McMahon +4 more
TL;DR: In this article, the authors examined the extent to which D4T produces neuropathic pain and examined pharmacological management with a standard opioid analgesic, i.e., a rightward shift of the morphine dose-response function.
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Nonopioid analgesics discovery and the Valley of Death: EMA401 from concept to clinical trial.
TL;DR: The obstacles impeding successful preclinical to clinical research translation in the novel analgesics field are addressed, and the discovery and development of EMA401, a peripherally restricted, highly selective, orally active, small-molecule AT2 receptor antagonist for relief of neuropathic pain are provided.
References
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Journal ArticleDOI
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TL;DR: Threshold measurement using the up-down paradigm, in combination with the neuropathy pain model, represents a powerful tool for analyzing the effects of manipulations of the neuropathic pain state.
Journal ArticleDOI
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TL;DR: The results support a revision of the NeuPSIG recommendations for the pharmacotherapy of neuropathic pain and allow a strong recommendation for use and proposal as first-line treatment in neuropathicPain for tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors, pregabalin, and gabapentin.
Journal ArticleDOI
Recommendations for the Pharmacological Management of Neuropathic Pain: An Overview and Literature Update
Robert H. Dworkin,Alec B. O'Connor,Joseph Audette,Ralf Baron,Geoffrey K. Gourlay,Maija Haanpää,Joel L. Kent,Elliot J. Krane,Elliot J. Krane,Alyssa Lebel,Robert M. Levy,Sean Mackey,John M. Mayer,Christine Miaskowski,Srinivasa N. Raja,Andrew S.C. Rice,Kenneth E. Schmader,Brett R. Stacey,Steven P. Stanos,Rolf-Detlef Treede,Dennis C. Turk,Gary A. Walco,Christopher D. Wells +22 more
TL;DR: A review of the evidence-based guidelines for the pharmacological treatment of neuropathic pain can be found in this article, where botulinum toxin, high-concentration capsaicin patch, lacosamide, selective serotonin reuptake inhibitors, and combination therapies are presented.
Journal ArticleDOI
Chemotherapy-induced peripheral neuropathy: A current review
TL;DR: The approach to peripheral neuropathy in patients with cancer is discussed and the clinical phenotypes and pathomechanisms of specific neurotoxic chemotherapeutic agents are addressed.
Journal ArticleDOI
Gabapentin for chronic neuropathic pain in adults
Philip J Wiffen,Sheena Derry,Rae Frances Bell,Andrew S.C. Rice,Thomas R. Tölle,Tudor Phillips,R Andrew Moore +6 more
TL;DR: Gabapentin is commonly used to treat neuropathic pain (pain due to nerve damage) and adverse effects in adults as discussed by the authors, and it has been shown that patients with substantial pain relief (at least 50% pain relief over baseline or very much improved on Patient Global Impression of Change scale (PGIC)) were more common with gabapentin than with placebo.