A Neural Circuit for Modulating Trigeminal Neuropathic Pain

We observed that a subpopulation of neurons in the parasubthalamic nucleus (PSTN), a poorly understood region in the posterior hypothalamus, was specifically activated by trigeminal nerve injury. Using anterograde and retrograde viral tracing techniques, we observed that the activated neurons in the PSTN projected to the deep mesencephalic nucleus (DpMe), a brainstem region involved in reward and pain processing. We further performed optogenetic stimulation of the PSTN-DpMe pathway and found that specific activation of this pathway inhibited the CCI-ION induced trigeminal neuropathic pain, suggesting that the activated neural circuit contributes to the modulation of such pain through descending pain inhibition. Moreover, we observed that NMDA receptor antagonism in the DpMe blocked the pain inhibition produced by optogenetic activation of the descending neural circuit.