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Nitecapone reduces development and symptoms of neuropathic pain after spinal nerve ligation in rats1
Authors:Oleg Kamburl  Pekka T. Männistöl  Anne M. Pusal  Mikko Käenmäkil  Eija A. Kalsol  Vesa K. Kontinenl
Affiliation:1. Division of Pharmacology and Toxicology, Faculty of Pharmacy, University of Helsinki, Finland;2. Department of Anaesthesia and Intensive Care Medicine, Helsinki University Central Hospital, Finland;3. Department of Pharmacology, Institute of Biomedicine, University of Helsinki, Finland
Abstract:Neuropathic pain is caused by damage or malfunctioning of the nervous system. It is fairly common and more resistant to treatment than other types of pain. Since nitecapone, an inhibitor of catechol‐O‐methyl‐transferase (COMT), has decreased neuropathic symptoms in diabetic rats, we studied its effects in another model of neuropathic pain, the spinal nerve ligation (SNL) model. Spinal nerves L5–6 were ligated in male Wistar rats under anaesthesia to produce the SNL model of neuropathic pain. Nitecapone (30 mg/kg, i.p.) or vehicle was administered once daily starting either 1 h before or 2 days after surgery and continued for 14–19 days. Threshold for mechanical allodynia was measured with the digital von Frey test and responses to cold stimuli with the acetone test, before surgery and every other day after it 1 h before drug administration. Mechanical and cold allodynia developed in all study groups. Both nitecapone treatments significantly reduced mechanical allodynia and withdrawal thresholds were 80–95% higher compared with the control group. In the acetone test, both nitecapone groups also showed less signs of cold allodynia than the control groups. In nitecapone‐naïve animals a single dose of nitecapone also reduced mechanical allodynia on the 14th day after the surgery. Nitecapone reduced the symptoms of neuropathic pain after the SNL, which is in line with the earlier study. Our results suggest that nitecapone and other COMT inhibitors should be studied further in the treatment of neuropathic pain.
Keywords:Neuropathic pain  Nitecapone  COMT  Allodynia  Spinal nerve ligation  Rat
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