Orexin-a modulates firing of rat rostral ventromedial medulla neurons: an in vitro study

The rostral ventromedial medulla (RVM) acts a key role in the descending inhibitory pain modulation. Neuropeptide orexin-A (ORXA) is confined to thousands of neurons in the lateral hypothalamus (LH). While RVM gets the orexinergic projections, the orexin receptors are also expressed in this structure. The aim of this study was to specify the cellular effects of ORXA on RVM neurons in vitro by using the whole cell patch-clamp recording. RVM neurons were classified into three types based on their electrophysiological characteristics. Type 1 neurons exhibited an irregular spontaneous activity which was interrupted by periods of pause in 25% of recorded neurons. Type 2 neurons did not show any spontaneous baseline activity (53.8% of recorded neurons). Type 3 neurons fired repetitively without interruption (51.2% of recorded neurons). ORXA had either inhibitory or excitatory effects on 53.8% (7/13) of type 1 neurons. ORXA excited 46.4% (13/28) of type 2 neurons and 27.3% (3/11) of type 3 neurons. The excitatory effect of ORXA observed in type 2 neurons was suppressed by an orexin 1 receptor (OXR1) antagonist, SB-334867. Briefly, we hypothesized that the ORXA mediated excitation and/or inhibition in RVM neurons might work as a mechanism to modulate pain processing by orexinergic neurons.