Modulation of trigeminal neuropathic pain by optogenetic inhibition of posterior hypothalamus in CCI-ION rat

Posterior hypothalamus (PH), an important part of the descending pain processing pathway, has been found to be activated in trigeminal autonomic cephalalgias. However, there are very few studies conducted and information regarding its implications in trigeminal neuropathic pain (TNP). Therefore, we aimed to ascertain whether optogenetic inhibition of PH could affect the outcomes of a chronic constriction injury in the infraorbital nerve (CCI-ION) rat model. Animals were divided into the TNP animal, sham, and naive-control groups. CCI-ION surgery was performed to mimic TNP symptoms, and the optogenetic or null virus was injected into the ipsilateral PH. In vivo single-unit extracellular recordings were obtained from both the ipsilateral ventrolateral periaqueductal gray (vlPAG) and contralateral ventral posteromedial (VPM) thalamus in stimulation OFF and ON conditions. Alterations in behavioral responses during the stimulation-OFF and stimulation-ON states were examined. We observed that optogenetic inhibition of the PH considerably improved behavioral responses in TNP animals. We found increased and decreased firing activity in the vlPAG and VPM thalamus, respectively, during optogenetic inhibition of the PH. Inhibiting PH attenuates trigeminal pain signal transmission by modulating the vlPAG and trigeminal nucleus caudalis, thereby providing evidence of the therapeutic potential of PH in TNP management.

Automated summary

Our study found that optogenetic inhibition of the posterior hypothalamus significantly improved behavioral responses in trigeminal neuropathic pain (TNP) animals. We also observed increased firing activity in the ventrolateral periaqueductal gray and decreased firing activity in the ventral posteromedial thalamus during optogenetic inhibition of the posterior hypothalamus. By modulating these areas, inhibiting the posterior hypothalamus can attenuate trigeminal pain signal transmission, providing evidence of its therapeutic potential in TNP management.