Contribution by DRt descending facilitatory pathways to maintenance of spinal neuron sensitization in rats

We investigated in different experimental rat models the potential facilitatory contribution of the medullary dorsal reticular nucleus (DRt) descending pathway to the expressions of the sensory spinal neuron sensitization such as increased spontaneous and noxious evoked activities, responsivity to heterotopic afferences stimulation and long lasting afterdischarges (ADs). We carried out experiments by recording from ipsilateral lumbar Wide Dynamic Range (WDR) neurons and by simultaneously monitoring the DRt neuron activity in neuropathic pain rats with chronic constriction injury of one sciatic nerve (CCI), in sham-operated and in "intact" rats. In particular, we recorded the spinal neuron spontaneous activities and the activities evoked by noxious stimulations of ipsi- and contralateral sciatic supplied areas before and during DRt activity blockade. Additionally, in "intact rats" we modulated WDR activity by iontophoretic NMDA to mimic CCI WDR hyperactivity without peripheral damage. We found that during DRt activity blockade in CCI rat neurons and in "intact" rat NMDA-treated neurons, the spontaneous activity was significantly reduced, the responses to contralateral sciatic area stimulation were reduced or suppressed, the responses to ipsilateral sciatic area were poorly affected (slightly reduced or unaffected), except for the poststimulus afterdischarges that were mostly suppressed. In sham-operated rats, the neuronal activity was not affected by DRt blockade. The finding that during the DRt nucleus blockade some expressions of spinal neurons sensitization, seemingly associated to sensory disorders in neuropathic pain, fade or extinguish designates a likely facilitatory role of DRt in the maintenance of neuronal sensitization and thus a contribution to neuropathic pain state.