A GABAergic Neuronal Thalamocortical Circuit Mediates the Relief of Diabetic Neuropathic Pain

摘要

Objective: Diabetic neuropathic pain(DNP) is a severe and clinically common form of neuropathic pain. Glutamatergic neurons in the ventral posterolateral nucleus(VPL) have been reported to participate in neuropathic pain development. However, the roles and mechanisms of VPL GABAergic neurons and neural circuits in DNP remain unclear. Methods: A streptozotocin(STZ)-induced DNP model was established in male rats. VPL neuronal activity was assessed by immunofluorescence staining and the von Frey test. The roles of VPL GABAergic neurons and their projections to the forelimb primary somatosensory cortex(S1FL) were investigated using optogenetic and chemogenetic approaches, viral tracing, and behavioral tests. Results: Both optogenetic(F2,18=376.155, P<0.001) and chemogenetic(F2,16=226.340, P<0.001) activation of VPL GABAergic neurons alleviated mechanical allodynia in male DNP model rats, indicating that VPL GABAergic neurons mediate antinociceptive effects. We identified a GABAergic thalamocortical circuit from the VPL projecting to the S1FL and demonstrated that this circuit mediates antinociceptive effects(optogenetic: F2,20=303.807, P<0.001; chemogenetic: F2,15=62.008, P<0.001) in DNP. Conclusion: These findings identify a GABAergic thalamocortical circuit involved in pain processing, reveal a mechanism of diabetic neuropathic pain pathogenesis and the role of thalamocortical circuits in analgesia, and provide new insights for analgesic development.

关键词

diabetic neuropathic pain / emotional experience / forelimb primary somatosensory cortex / GABAergic neurone / thalamocortical circuit / ventral posterolateral nucleus