[Effect of Electroacupuncture Intervention on CaMK II-CREB Pathway in Spinal Cord in Rats with Spared Nerve Injury].

Objective: To observe the effect of electroacupuncture (EA) stimulation of "Weizhong" (BL 40)-"Huantiao" (GB 30) on expression of phosphorylated calcium/calmodulin dependent protein kinase II (p-CaMK II) and cAMP response element binding protein (p-CREB) in the spinal cord in rats with spared nerve injury (SNI), so as to explore its mechanism underlying easing neuropathic pain.

Methods: Sixty SD rats were randomly divided into five groups: control (sham-operation) , model, EA, AP-5 (a NMDA receptor antagonist) and L-NAME (a non-selective nitric oxide synthase, NOS inhibitor) (n = 12 in each group). The neuropathic pain model was established by sectioning the right tibal nerve and common peroneal nerve. EA intervention (2 Hz, 1 mA, increasing 1 mA/10 min) was applied to "Weizhong" (BL 40) and "Huantiao" (GB 30) on the injured side for 30 min, once a day for 7 days. Rats of the AP-5 and L-NAME groups were treated by intragastric administration of AP-5 (0.7 mg · kg(-1) · d(-1)) and L-NAME (60 mg · kg(-1) · d(-1)) respectively from the 11 th day after operation, once daily for 7 days. The mechanical pain thresholds were measured before the SNI procedure (baseline) and at the 10th and 16th day after the procedure. The expression of p-CaMK II protein and p-CREB protein and gene of the spinal cord (L4-L6 segments) was determined by Western blot and fluorescence quantitative-polymerase chain reaction (PCR), separately.

Results: In comparison to the control group, the mechanical pain threshold was significantly decreased in the model group (P < 0.01). After EA intervention, the mechanical pain thresholds of the EA, AP-5 and L-NAME groups were obviously increased (P < 0.01, P < 0.05) on day 16 post SNI procedure. The expression levels of p-CaMK II and p-CREB proteins and CREB mRNA in the spinal cord were significantly higher in the model group than in the control group (P < 0.05). Compared with the model group, the expression levels of spinal p-CaMK II and p-CREB proteins and CREB mRNA were obviously down-regulated in the EA group (P < 0.05), but not in the AP-5 group and the L-NAME group (P > 0.055.

Conclusion: EA intervention of BL 40-GB 30 may alleviate pain in neuropathic pain rats, which may be related to its effects in down-regulating spinal CaMK II-CREB pathway function.