Pre-emptive anti-hyperalgesic effect of electroacupuncture in carrageenan-induced inflammation: Role of nitric oxide

Central sensitization theory has been defined as pivotal for understanding the excitability changes in central neurons following peripheral inflammation or neuropathic injury. Considerable evidence has demonstrated that activation of the N-methyl-d-aspartate (NMDA) subtype of glutamate receptors and subsequent nitric oxide (NO) production are the key in these changes. Consequently, neuromodulator drugs have been developed during the last decades. The electroacupuncture (EA) that acts as biochemical modulator in the spinal horn cord would prevent these changes. The aim of this study was to determine the thermal anti-hyperalgesic effect of EA (10 Hz, 3 mA) and its combination with l-NAME as nitric oxide synthase (NOS) inhibitor in carrageenan-induced hyperalgesia in rats. Also, it investigated the changes in the plasmatic concentrations of NO metabolites. Moreover, the EA combination with sub-effective dose of ketamine as a NMDA antagonist was tested. The EA pre-treatment conducted in unsedated, unrestrained and conscious animals showed a thermal anti-hyperalgesic effect in correspondence with plasmatic increase of NO metabolites. The l-NAME (30 mg/kg) pre-administration decreased significantly the plasmatic concentrations of NO2−/NO3− and suppressed the anti-hyperalgesic effect of EA. The combination of EA with ketamine enhanced the anti-hyperalgesic effect. These data constitute the first report that suggested the participation, at least in part, of the l-arginine–NOS–NO–GMPc pathway activation in anti-hyperalgesic effect of EA in carrageenan-induced inflammation model.