A nigra–subthalamic circuit is involved in acute and chronic pain states

Abstract

Reversal of the attenuated SNrGABA−STNGlu projection mitigates pain-related behaviors in acute and chronic inflammatory pain and neuropathic pain states.

A nigro–subthalamo–parabrachial pathway modulates pain-like behaviors

“…Similarly, we previously reported that SNr neurons innervated by the STN partially mediate hyperalgesia in parkinsonian mice 20 . Contrary to these studies 20,61 , but similar to another study 37 , we observed that stimulation of SNr neurons led to analgesic effects. These results suggest that SNr neurons are diverse in terms of their involvement in pain perception, depending on which neural pathway they belong to.…”

“…That is, those innervated by the LPB and STN may facilitate the transmission of pain signals, whereas those innervating the STN suppress pain perception. Indeed, two subsets of SNr neurons that respectively innervate STN neurons and are innervated by STN neurons are largely separated 37 . Taking the previous studies together with our current finding, we propose that SNr GABA neurons receive pain-related information from the LPB and, in turn, regulate the downstream STN-LPB pathway and pain responses.…”

“…1) may provide a drive for enhancement of the STN-LPB projection. Based on our recent study demonstrating the SNr-STN projection confers an analgesic effect in several pain conditions 37 , we hypothesized that compromised inhibitory synaptic inputs to STN neurons may be associated with their hyperactivity in various pain states. Indeed, we found a reduced frequency but not amplitude of miniature inhibitory postsynaptic currents (mIPSCs) in STN neurons, compared with those in sham mice (Fig.…”

“…von Frey filaments with fiber force between 0.1-4 g were used to measure mechanical paw withdrawal threshold (PWT) of both hind paws. The 50% threshold was determined by the up-down method 20,37,66 .…”

“…The STN receives excitatory and inhibitory inputs from various cortical and subcortical areas 21,23,35,36 . Our recent study found that activation of GABAergic inputs from the substantia nigra pars reticulata (SNr) to the STN reduced pain-like hypersensitivity during inflammatory and neuropathic pain states 37 . In particular, neuronal activity in the SNr was compromised under neuropathic pain condition, indicating a role of GABAergic inputs in the STN in the modulation of pain signals.…”