Functional involvement of nucleus tractus solitarii neurons projecting to the parabrachial nucleus in trigeminal neuropathic pain

Peripheral nerve injury can induce neuro-plastic changes in the central nervous system and result in neuropathic pain. This study investigated functional involvement in dorsal paratrigeminal nucleus (dPa5) and nucleus tractus solitarii (NTS) neurons projecting to the parabrachial nucleus (PBN) after trigeminal nerve injury. Anatomical quantification was performed based on phosphory-lated extracellular signal-regulated kinase (pERK) expression underlying orofacial neuropathic pain associated with infraorbital nerve chronic constriction injury (ION-CCI) in rats. ION-CCI rats exhibited heat and mechanical hypersensitivity in the ipsilateral upper lip. After injection of retrograde tracer fluorogold (FG) into the contralateral PBN, ION-CCI rats received capsaicin or noxious mechanical stimulation to the upper lip. The total number of FG-labeled neurons in dPa5 and NTS did not change after ION-CCI, and pERK expression in dPa5 did not differ between sham and ION-CCI rats. In the NTS contralateral to ION-CCI, the number of pERK-immunoreactive neurons and percentage of pERK-immunoreactive FG-labeled PBN projection neurons were increased after capsaicin stimulation in ION-CCI rats. The present findings suggest that enhanced noxious inputs from the NTS to the PBN after trigeminal nerve injury modulates PBN neuron activity, which accompanies the affective components of orofacial neuropathic pain.