Electroacupuncture alleviates neuropathic pain and long-term cognitive impairment via the rACC-vlPAG neural circuit.

AIMS: Chronic pain and cognitive dysfunction are highly correlated. Electroacupuncture (EA) can alleviate chronic neuropathic pain and cognitive impairments. However, the neural mechanisms underlying EA treatment for comorbid neuropathic pain and cognitive dysfunction remain unclear.

METHODS

A rat model of neuropathic pain was induced by spared nerve injury (SNI). In vivo, fiber-optic calcium imaging was used to observe changes in the activity of CaMKII-positive neurons in the rostral anterior cingulate cortex (rACC). Chemogenetic approaches were employed to investigate the mechanisms involving the rACC and ventrolateral periaqueductal gray (vlPAG) in neuropathic pain and cognitive dysfunction, as well as the interventional effects of EA.

RESULTS

EA significantly relieved chronic neuropathic pain and long-term cognitive impairments induced in SNI rats, increasing the activity of CaMKII-positive neurons in the rACC brain region. Under neuropathic pain conditions, inhibiting the rACCCaMKII-vlPAG neural circuit effectively alleviated neuropathic pain and long-term cognitive impairments, whereas activation did not. Additionally, 2 Hz EA effectively mitigated neuropathic pain and long-term cognitive impairments in this state, and activating the rACCCaMKII-vlPAG neural circuit reversed the interventional effects of EA.

CONCLUSION

SNI rats developed comorbid neuropathic pain and cognitive dysfunction. The rACCCaMKII-vlPAG neural circuit is involved in the regulation of neuropathic pain and long-term cognitive dysfunction. 2 Hz EA may intervene in neuropathic pain and cognitive impairments by inhibiting the rACCCaMKII-vlPAG neural circuit.