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Anti-allodynic effect of the flavonoid myricetin in a rat model of neuropathic pain: Involvement of p38 and protein kinase C mediated modulation of Ca(2)+ channels

Flavonoids are increasingly ingested by the population as chemotherapeutic and anti-inflammatory agents. Myricetin is a naturally occurring flavonoid known for its anti-neoplastic and anti-inflammatory effects. Recently, behavioral studies indicate a potential analgesic effect in animal models of pain. Pilot studies suggest a flavonoid-induced modulation of intracellular protein kinases and interactions with voltage activated calcium channels. The aim of this study was to investigate the analgesic effect of myricetin in a neuropathic pain model (spinal nerve ligation, SNL) in rats. To identify potential mechanisms of action, in vitro whole cell patch-clamp recordings of isolated rat dorsal root ganglia (DRG) neurons were performed to analyze the modulation of voltage activated calcium channel currents (I(Ca(V))) and the influence of intracellular kinase phosphorylation such as p38 mitogen-activated protein kinase (p38) or protein kinase C (PKC). In vivo, a single injection of myricetin (0.1-10 mg/kg i.p.) reduced SNL-induced mechanical allodynia and thermal hyperalgesia lasting for several hours. In vitro, I(Ca(V)) (depolarization from -80 to 0 mV) were reduced (10-56%) by low (0.1-5 muM) concentrations of myricetin. This decrease was abolished by blockade of PKC (20 muM chelerythrine for 30 min), but not of p38 (10 muM SB203580 for 30 min). In contrast, higher (10-100 muM) concentrations of myricetin induced an increase of I(Ca(V)) (20-40%), which was blocked by inhibition of p38, but not of PKC. We conclude that myricetin transiently reduces established neuropathic pain behavior. This analgesic effect may be related to its PKC-induced decrease of I(Ca(V)) in DRG neurons

Keywords : Analgesics,Analgesics,Non-Narcotic,Animals,antagonists & inhibitors,Anti-Inflammatory Agents,Behavior,Animal,Calcium,Calcium Channels,cytology,drug effects,drug therapy,Electrophysiology,enzymology,Flavonoids,Ganglia,Spinal,Germany,Hot Temperature,Hyperalgesia,Ligation,Male,metabolism,Neuralgia,Neurons,p38 Mitogen-Activated Protein Kinases,Pain,Patch-Clamp Techniques,pharmacology,Physical Stimulation,Protein Kinase C,Protein Kinase Inhibitors,Rats,Rats,Wistar,Spinal Nerves,, Effect,Flavonoid,Myricetin, back care london

Date of Publication : 2010 Nov

Authors : Hagenacker T;Hillebrand I;Wissmann A;Busselberg D;Schafers M;

Organisation : Department of Neurology, University of Duisburg-Essen, Hufelandstr. 55, 45122 Essen, Germany

Journal of Publication : Eur J Pain

Pubmed Link : https://www.ncbi.nlm.nih.gov/pubmed/20471878

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