Nitecapone reduces development and symptoms of neuropathic pain after spinal nerve ligation in rats. 2011

Oleg Kambur, and Pekka T Männistö, and Anne M Pusa, and Mikko Käenmäki, and Eija A Kalso, and Vesa K Kontinen
Division of Pharmacology and Toxicology, Faculty of Pharmacy, University of Helsinki, Finland. oleg.kambur@helsinki.fi

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 1h 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 1h 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.

UI MeSH Term Description Entries
D008297 Male Males
D009437 Neuralgia Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. Nerve Pain,Neurodynia,Paroxysmal Nerve Pain,Neuralgia, Atypical,Neuralgia, Iliohypogastric Nerve,Neuralgia, Ilioinguinal,Neuralgia, Perineal,Neuralgia, Stump,Neuralgia, Supraorbital,Neuralgia, Vidian,Neuropathic Pain,Atypical Neuralgia,Atypical Neuralgias,Iliohypogastric Nerve Neuralgia,Iliohypogastric Nerve Neuralgias,Ilioinguinal Neuralgia,Ilioinguinal Neuralgias,Nerve Neuralgia, Iliohypogastric,Nerve Neuralgias, Iliohypogastric,Nerve Pain, Paroxysmal,Nerve Pains,Nerve Pains, Paroxysmal,Neuralgias,Neuralgias, Atypical,Neuralgias, Iliohypogastric Nerve,Neuralgias, Ilioinguinal,Neuralgias, Perineal,Neuralgias, Stump,Neuralgias, Supraorbital,Neuralgias, Vidian,Neurodynias,Neuropathic Pains,Pain, Nerve,Pain, Neuropathic,Pain, Paroxysmal Nerve,Pains, Nerve,Pains, Neuropathic,Pains, Paroxysmal Nerve,Paroxysmal Nerve Pains,Perineal Neuralgia,Perineal Neuralgias,Stump Neuralgia,Stump Neuralgias,Supraorbital Neuralgia,Supraorbital Neuralgias,Vidian Neuralgia,Vidian Neuralgias
D010422 Pentanones 5-carbon straight-chain or branched-chain ketones. Diethyl Ketones,Methyl Propyl Ketones,Ketones, Diethyl,Ketones, Methyl Propyl,Propyl Ketones, Methyl
D010812 Physical Stimulation Act of eliciting a response from a person or organism through physical contact. Stimulation, Physical,Physical Stimulations,Stimulations, Physical
D002396 Catechols A group of 1,2-benzenediols that contain the general formula R-C6H5O2. Pyrocatechols,o-Dihydroxybenzenes,ortho-Dihydroxybenzenes,o Dihydroxybenzenes,ortho Dihydroxybenzenes
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D006930 Hyperalgesia An increased sensation of pain or discomfort produced by minimally noxious stimuli due to damage to soft tissue containing NOCICEPTORS or injury to a peripheral nerve. Hyperalgesia, Tactile,Hyperalgesia, Thermal,Hyperalgia,Hyperalgia, Mechanical,Hyperalgia, Primary,Hyperalgia, Secondary,Allodynia,Allodynia, Mechanical,Allodynia, Tactile,Allodynia, Thermal,Hyperalgesia, Mechanical,Hyperalgesia, Primary,Hyperalgesia, Secondary,Hyperalgesic Sensations,Mechanical Allodynia,Mechanical Hyperalgesia,Tactile Allodynia,Thermal Allodynia,Allodynias,Hyperalgesias,Hyperalgesias, Thermal,Hyperalgesic Sensation,Mechanical Hyperalgia,Mechanical Hyperalgias,Primary Hyperalgia,Primary Hyperalgias,Secondary Hyperalgia,Secondary Hyperalgias,Sensation, Hyperalgesic,Sensations, Hyperalgesic,Thermal Hyperalgesia
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013127 Spinal Nerves The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. Nerve, Spinal,Nerves, Spinal,Spinal Nerve
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats

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