The Effects of Electroacupuncture on the Apelin/APJ System in the Spinal Cord of Rats With Inflammatory Pain

BACKGROUND:Electroacupuncture (EA) is widely applied for pain management, but the analgesic effects of EA have not been fully elucidated. In this study, we investigated the effect of EA on inflammatory pain caused by intraplantar injection of complete Freund’s adjuvant (CFA) and apelin/APJ expression in the spinal cord of rats. METHODS:The study was conducted in 3 parts. In part 1, Sprague-Dawley rats were divided into 4 groups (n = 10)sham, CFA, EA (CFA + 2 Hz EA at acupoints), and NA-EA (CFA + acupuncture without electrical stimulation). The time courses of mechanical and thermal sensitivity were determined. The protein and messenger RNA (mRNA) levels of apelin and APJ in the spinal cord were assayed by Western blotting and real-time polymerase chain reaction, respectively. In part 2, the rats were divided into 5 groups (n = 7–8)sham, CFA, EA, F13A (CFA + intrathecal injection of F13A), and EA-F13A (CFA + EA + intrathecal injection of F13A). In part 3, the rats were divided into 5 groups (n = 8)sham, CFA, EA, apelin-13 (CFA + intrathecal injection of apelin-13), and EA + apelin-13 (CFA + EA + intrathecal injection of apelin-13). RESULTS:EA treatment exhibited significant antinociceptive effects (mechanical sensitivitymean difference [99% confidence interval {CI}]5.86 [4.96–6.77]; thermal sensitivitymean difference [99% CI]2.45 [0.91–4.00]; EA versus CFA) and mitigated the CFA-induced reduction of apelin and APJ protein and mRNA expression in the spinal cord. Furthermore, intrathecal injection of the apelin/APJ system antagonist F13A blocked the analgesic effect of EA (mechanical sensitivitymean difference [99% CI]8.99 [5.81–12.17]; thermal sensitivitymean difference [99% CI]4.22 [1.33–7.12]; EA versus EA-F13A). When EA was combined with apelin-13 through intrathecal administration, it was more potent in reducing mechanical allodynia (mean difference [99% CI]5.98 [2.38–9.57], EA + apelin-13 versus apelin-13; mean difference [99% CI]4.29 [0.72–7.87], EA + apelin-13 versus EA) and thermal hyperalgesia (mean difference [99% CI]5.23 [2.19–8.28], EA + apelin-13 versus apelin-13; mean difference [99% CI]6.43 [3.38–9.48], EA + apelin-13 versus EA). CONCLUSIONS:EA stimulation could alleviate inflammatory pain, at least in part, by restoring apelin and APJ mRNA and protein expression levels, which are downregulated in the CFA pain model.