Pain induces stable, active microcircuits in the somatosensory cortex that provide a therapeutic target

Sustained neuropathic pain from injury or inflammation remains a major burden for society. Rodent pain models have informed some cellular mechanisms increasing neuronal excitability within the spinal cord and primary somatosensory cortex (S1), but how activity patterns within these circuits change during pain remains unclear. We have applied multiphoton in vivo imaging and holographic stimulation to examine single S1 neuron activity patterns and connectivity during sustained pain. Following pain induction, there is an increase in synchronized neuronal activity and connectivity within S1, indicating the formation of pain circuits. Artificially increasing neuronal activity and synchrony using DREADDs reduced pain thresholds. The expression of N-type voltage-dependent Ca2+ channel subunits in S1 was increased after pain induction, and locally blocking these channels reduced both the synchrony and allodynia associated with inflammatory pain. Targeting these S1 pain circuits, via inhibiting N-type Ca2+ channels or other approaches, may provide ways to reduce inflammatory pain.

Automated summary

This research utilizes multiphoton in vivo imaging and holographic stimulation to explore the changes in neuronal activity and connectivity within S1 during sustained pain, revealing the formation of pain circuits. Increasing neuronal activity and synchrony artificially can reduce pain thresholds, while locally blocking N-type Ca2+ channels can decrease synchrony and allodynia associated with inflammatory pain. Targeting these S1 pain circuits may offer new ways to alleviate inflammatory pain.