Effect of Electroacupuncture on Activation of p38MAPK in Spinal Dorsal Horn in Rats with Complete Freund's Adjuvant-Induced Inflammatory Pain

Abstract

Activation of mitogen-activated protein kinases (MAPKs), especially p38 MAPK, plays an important role in the development of central sensitization related to persistent inflammatory pain. Electroacupuncture (EA) is well known to relieve persistent inflammatory pain. However, little is known about relationship between EA and p38 MAPK. Inflammatory pain rat model was induced by intraplantar injection of complete Freund's adjuvant (CFA). Male adult SD rats were randomly divided into the saline group, CFA group, and CFA + EA group. EA (constant saquare wave, 2 Hz and 100 Hz alternating frequencies, intensities ranging from 1 to 2 mA) was applied to bilateral “Zusanli” (ST 36) and “Kunlun” acupoints (BL 60) for 30 min, once per day. The paw edema and paw withdrawal threshold (PWT) were measured at preinjection and days postinjection 1, 3, and 14. Spinal p-p38MAPK- immunoreactivty (p-p38MAPK-IR) cells were detected by immunohistochemistry at postinjection day 3 and 14. EA significantly inhibited paw edema at postinjection days 14 and increased PWT at postinjection days 3 and 14. Moreover, the increasing number of spinal p-p38MAPK-IR cells which was induced by CFA injection was suppressed by EA stimulation. These results indicate that anti-inflammatory and analgesic effect of EA might be associated with its inhibition of spinal p38 MAPK activation and thereby provide a potential mechanism for the treatment of inflammatory pain by EA.

Mechanisms of Acupuncture–Electroacupuncture on Persistent Pain

“…106,107 Activated p38 MAPK is known to play an important role during nociception and is translocated to the nucleus to phosphorylate transcriptional factors such as ATF-2. 108 Neurokinin-1 receptors and proinflammatory cytokines such as IL-1β and TNF-α contribute to p38 MAPK activation in the spinal cord.…”

Inhibition of Spinal Microglia and Astrocytes Contributes to the Anti-Allodynic Effect of Electroacupuncture in Neuropathic Pain Induced by Spinal Nerve Ligation

“…Paw withdrawal thresholds (PWTs) were measured according to the Original paper method described by Liang et al 9 At the end of the 14-day period, four to five rats from each group of eight to nine were euthanased and underwent immunohistochemical analysis of their spinal cord tissues. In the True-SNL and True-SNL+EA groups an additional 10 animals per group were euthanased in the same manner at day 3 (n=5 each) and day 7 (n=5 each).…”

“…Electroacupuncture (EA), a modified acupuncture technique, has been used for several decades in the treatment of chronic pain. [8][9][10] Spinal nerve ligation (SNL) is a widely used model of neuropathic pain, which can be alleviated by repeated EA. 10 11 In rats with SNL, spinal astrocytes and microglia on the side ipsilateral to the lesion were heavily stained and appeared to show an activated state, 12 and intrathecal injection of minocycline significantly attenuated mechanical allodynia in this model.…”

Intervention of Electroacupuncture on Spinal p38 MAPK/ATF-2/VR-1 Pathway in Treating Inflammatory Pain Induced by CFA in Rats

“…However, the underlying mechanisms of EA for inflammatory pain are still not completely understood. We previously reported that EA could attenuate CFA-induced inflammatory pain, at least in part, through suppressing numbers of p-p38 MAPK IR-cells in spinal cord [22]. In this study, we first used a rat CFA model to observe whether p38 MAPK signal transduction pathway in spinal cord plays an important role in inflammatory pain, and then to investigate whether EA may relieve inflammatory pain by counteracting the activation of p38 MAPK signal transduction pathway.…”