Active Ingredients: Gabapentin
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More recently, an additional mechanism of action has been suggested for gabapentin and pregabalin. Pre-Clinical Models of NON-GI Neuropathic Pain The anti-allodynic and anti-hyperalgesic properties of gabapentin and pregabalin have been established in a wide range of animal models and the literature is too extensive to review here.
Interestingly, in a study of both sympathetically-maintained and sympathetically-independent neuropathic pain, pregabalin was particularly potent at inhibiting both tactile and cold allodynia when given by the intrathecal route, suggesting a predominantly spinal site of action, although the involvement of supraspinal centers cannot be ruled out Han et al.
Pregabalin was unable to inhibit cold allodynia in the model of sympathetically-independent neuropathic pain when given via the intraperitoneal route Han et al.
Further, pregabalin was also able to inhibit central sensitization of the spinal neurons induced by application of bee venom. Spinal transection confirmed that the effect of pregabalin in this study was likely to involve supraspinal centers, mediated through descending inhibitory controls You et al.
Pre-Clinical Models of GI Sensation and Motility Following the demonstration of the efficacy of gabapentin and pregabalin in animal models of neuropathic pain, investigations of the profile of these agents in small animal models of visceral pain followed.
Initial focus was on understanding whether gabapentin and pregabalin might have utility in the treatment of IBS and so studies focused on models of rectal or colonic hypersensitivity. Caution needs to be applied when interpreting these data given the recent history of notable failure of these models to predict the effects of other new drugs on human pain and discomfort e.
The hypersensitivity can be demonstrated following rectal distension with a small balloon and is manifest as both allodynia as well as hyperalgesia. These observations were then extended in a more chronic model of colonic allodynia Diop et al.
Histological analysis revealed an inflammatory response in the proximal colon, characterized by the presence of inflammatory cells, necrosis, and hyperemia, 3 days after dosing with TNBS. This response had substantially diminished by day 7 and in the distal colon, no increase in inflammatory cells was observed at any time point.
Hyperemia appeared to persist to day 7, the study day for these experiments.
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These data raise the safety that in this model, pregabalin hives spinal sensitization and so patches the development of hyperalgesia.