Nicotinamide in a model of osteoarthritis – mechanism of analgesic action and its effect on cognition and reduction of oxidative stress in the rat heart

Nicotinamide has demonstrated pain-relieving effectiveness in osteoarthritis patients (OA). However, there are no data about the mechanism of its analgesic effect. We aimed to examine the behavioral/cardiac effects of nicotinamide alone and in combination with duloxetine (established antidepressant for OA) or vortioxetine (novel antidepressant) in an OA model, and its impact on the expression of central/peripheral pain mediators. In the monoiodoacetate-induced rat model of knee OA, pain behavior was assessed with weight-bearing, von Frey and acetone tests. Nicotinamide, antidepressants and their combinations were administered orally for 28 days. Transcript levels of pain-related biomarkers ( Il-1β , Tnf-α , Ngf , Bdnf and Tac1 encoding substance P) and cardiac oxidative stress markers were determined after behavioral experiments. Burrowing and novel-object-recognition tests were used to assess the effects of drugs/drug combinations on animal well-being and cognitive performance, respectively. Nicotinamide was effective as duloxetine/vortioxetine in suppressing pain behavior in OA animals. Its antihyperalgesic effect seems to be exerted by decreasing mRNA expression of pro-inflammatory mediators ( Ngf, Bdnf and Tac1 ) involved in central pain pathway sensitization. Nicotinamide enhanced cognitive performance, and did not affect burrowing in OA animals. It decreased cardiac oxidative stress parameters in OA rats. Nicotinamide in combination with duloxetine/vortioxetine did not affect significantly their behavioral effects. In combination with duloxetine, nicotinamide attenuated cardiac oxidative stress parameters in comparison with those in duloxetine treatment alone. Our results clarify the mechanism of nicotinamide analgesic effect in OA, and support its use as a cardioprotective adjuvant to duloxetine in prolonged treatment.