Standard analgesics reverse burrowing deficits in a rat CCI model of neuropathic pain, but not in models of type 1 and type 2 diabetes-induced neuropathic pain
| Autor: | Stacey Anne Gould, Luke A. Bryden, Anton Pekcec, Henri Doods, Thomas Christoph, Kris Rutten |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Gabapentin Analgesic Pregabalin Type 2 diabetes Motor Activity Diabetes Mellitus Experimental Random Allocation 03 medical and health sciences Behavioral Neuroscience 0302 clinical medicine Diabetes mellitus parasitic diseases Animals Medicine Rats Wistar Analgesics Behavior Animal business.industry fungi musculoskeletal system medicine.disease Streptozotocin Rats Zucker Diabetes Mellitus Type 1 030104 developmental biology Diabetes Mellitus Type 2 Anesthesia Neuropathic pain Morphine Neuralgia business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Behavioural Brain Research. 350:129-138 |
| ISSN: | 0166-4328 |
| Popis: | Background Burrowing is a rodent behavior validated as a robust and reproducible outcome measure to infer the global effect of pain in several inflammatory pain models. However, less is known about the effect of analgesics on burrowing in neuropathic pain models and no studies have determined burrowing performance in models of diabetes-associated neuropathic pain. Objective To compare the sensitivity of the burrowing assay in different neuropathic pain models: mononeuropathic pain and diabetic polyneuropathy. Methods Burrowing performance was determined by the amount of substrate left in a hollow tube by rats with chronic constriction injury (CCI). In addition, burrowing performance, locomotion and pain development was assessed in the Zucker diabetic fatty (ZDF) rat model, resembling type-2 diabetes. Efficacy of clinically-active reference drugs (opioids, gabapentin and/or pregabalin) were investigated in these models. Burrowing behavior was additionally assessed in a second model, induced by streptozotocin (STZ) treatment, resembling type-1 diabetes. Results In the CCI model, moderate but consistent burrowing deficits were observed that persisted over a period of ≥20 days. Systemic administration of morphine, pregabalin and gabapentin reversed this deficit. In contrast, none of the reference drugs improved marked burrowing deficits detected in ZDF rats, and pregabalin did not reverse severe burrowing deficits observed in STZ rats. Conclusions Burrowing performance cannot necessarily be used as pain-related readout across pain models and largely depends on the model used, at least in models of neuropathy. Specifically, analgesic drug effects might be masked by general diabetes-associated alteration of the animals’ well-being, resulting in false negative outcomes. |
| Databáze: | OpenAIRE |
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