BMC Complement Altern Med. 2013 Jun 15;13:134. doi: 10.1186/1472-6882-13-134.
Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacologic treatment for pain relief. In previous animal studies, TENS effectively alleviated Complete Freund's Adjuvant (CFA)- or carrageenan-induced inflammatory pain. Although TENS is known to produce analgesia via opioid activation in the brain and at the spinal level, few reports have investigated the signal transduction pathways mediated by TENS. Prior studies have verified the importance of the activation of extracellular signal-regulated kinase (ERK) signal transduction pathway in the spinal cord dorsal horn (SCDH) in acute and persistent inflammatory pains. Here, by using CFA rat model, we tested the efficacy of TENS on inhibiting the expressions of p-ERK1/2 and of its downstream cyclooxygenase-2 (COX-2) and the level of prostaglandin E2 (PGE2) at spinal level.
Rats were randomly divided into control, model and TENS groups, and injected subcutaneously with 100 μl CFA or saline in the plantar surface of right hind paw. Rats in the TENS group were treated with TENS (constant aquare wave, 2 Hz and 100 Hz alternating frequencies, intensities ranging from 1 to 2 mA, lasting for 30 min each time) at 5 h and 24 h after injection. Paw withdrawal thresholds (PWTs) were measured with dynamic plantar aesthesiometer at 3d before modeling and 5 h, 6 h, and 25 h after CFA injection. The ipsilateral sides of the lumbar spinal cord dosral horns were harvested for detecting the expressions of p-ERK1/2 and COX-2 by western blot analysis and qPCR, and PGE2 by ELISA.
CFA-induced periphery inflammation decreased PWTs and increased paw volume of rats. TENS treatment significantly alleviated mechanical hyperalgesia caused by CFA. However, no anti-inflammatory effect of TENS was observed. Expression of p-ERK1/2 protein and COX-2 mRNA was significantly up-regualted at 5 h and 6 h after CFA injection, while COX-2 and PGE2 protein level only increased at 6 h after modeling. Furthermore, the high expression of p-ERK1/2 and COX-2, and over-production of PGE2 induced by CFA, were suppressed by TENS administration.
TENS may be an effective therapy in controlling inflammatory pain induced by CFA. Its analgesic effect may be associated with the inhibition of activation of the spinal ERK1/2-COX-2 pathway.
经皮神经电刺激（TENS）是一种非药物治疗疼痛的方法。在之前的动物研究中，TENS 有效缓解了完全弗氏佐剂（CFA）或角叉菜胶引起的炎症性疼痛。虽然 TENS 通过在大脑和脊髓水平激活阿片样物质来产生镇痛作用，但很少有报道研究 TENS 介导的信号转导途径。先前的研究已经证实，细胞外信号调节激酶（ERK）信号转导通路在脊髓背角（SCDH）中在急性和持续性炎症疼痛中的激活的重要性。在这里，我们使用 CFA 大鼠模型，测试 TENS 抑制脊髓水平 p-ERK1/2 及其下游环氧化酶-2（COX-2）表达和前列腺素 E2（PGE2）水平的功效。
大鼠随机分为对照组、模型组和 TENS 组，在右后足底皮下注射 100 μl CFA 或生理盐水。TENS 组大鼠在注射后 5 小时和 24 小时接受 TENS（恒方波，2 Hz 和 100 Hz 交替频率，强度为 1 至 2 mA，每次持续 30 分钟）治疗。在建模前 3 天和 CFA 注射后 5 小时、6 小时和 25 小时，使用动态足底触觉计测量足底退缩阈值（PWT）。通过 Western blot 分析和 qPCR 检测腰椎脊髓背角 p-ERK1/2 和 COX-2 的表达，通过 ELISA 检测 PGE2 的表达。
CFA 诱导的外周炎症降低了大鼠的 PWT 并增加了足部容积。TENS 治疗显著缓解了 CFA 引起的机械性痛觉过敏。然而，TENS 没有抗炎作用。CFA 注射后 5 小时和 6 小时，p-ERK1/2 蛋白和 COX-2 mRNA 的表达明显上调，而 COX-2 和 PGE2 蛋白水平仅在建模后 6 小时增加。此外，CFA 诱导的 p-ERK1/2 和 COX-2 的高表达和 PGE2 的过度产生被 TENS 给药抑制。
TENS 可能是控制 CFA 诱导的炎症性疼痛的有效治疗方法。其镇痛作用可能与抑制脊髓 ERK1/2-COX-2 通路的激活有关。
