Intraganglionic injection of a nitric oxide donator induces afferent mechanical sensitization that is attenuated by palmitoylethanolamide

Abstract

The aim of this article is to investigate whether the nitric oxide (NO) donator diethylenetriamine/nitric oxide (DETA/NO) affects trigeminal sensory processing through the trigeminal ganglion in part by activating trigeminal satellite glial cells (SGCs) and whether this effect is attenuated by the anti-inflammatory compound palmitoylethanolamide (PEA). DETA/NO was administered to isolated rat trigeminal SGCs invitro, and injected into the rat trigeminal ganglion invivo, in the presence or absence of PEA. Administration of DETA/NO (1000 µM) increased the release of prostaglandin E2 by SGCs. PEA (1 and 10 µM) significantly attenuated prostaglandin E2 release. Two intraganglionic injections of DETA/NO (10 mM, 3 µl) or prostaglandin E2 at a 30-minute interval did not evoke discharge in trigeminal ganglion neurons that innervate the rat jaw-closer muscles, but did reduce the mechanical activation threshold of their peripheral endings by 30%-50%. Intravenous administration of PEA (1 mg/kg) or ketorolac (0.5 mg/kg) prevented DETA/NO-induced afferent mechanical sensitization. Elevation of NO in the trigeminal ganglion results in the sensitization of the peripheral endings of masticatory muscle nociceptors to mechanical stimulation through a mechanism that involves prostaglandin E2 release from SGCs. Attenuation of this sensitization by PEA suggests a possible option for acute management of craniofacial pain and headache.