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.
Highlights
The mitogen-activated protein kinases (MAPKs) are important for intracellular signal transduction and play pivotal roles in mediating the generation and maintenance of pain [1]
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
It is shown that phosphorylated p38 (p-p38) MAPK, the active form of p38 MAPK, increases in spinal cord after peripheral inflammation which is induced by complete Freund’s adjuvant (CFA) [4], bee-venom [5], formalin [3, 6], or capsaicin [7]
Summary
The mitogen-activated protein kinases (MAPKs) are important for intracellular signal transduction and play pivotal roles in mediating the generation and maintenance of pain [1]. Intrathecal administration of a p38 MAPK inhibitor into spinal cord has been shown to effectively reduce pain behavior associated with the peripheral inflammation [3, 8,9,10]. The underlying mechanisms of EA analgesia are still not completely understood, and the influence of EA on p38 MAPK activation in spinal cord which is associated with inflammatory pain is unclear. Injection of complete Freund’s adjuvant (CFA) into a rat’s hind paw provides a very good animal model to study the mechanism of inflammatory pain [16]. Evidence-Based Complementary and Alternative Medicine we used a rat CFA model to observe the anti-inflammatory and analgesic effect of EA and to investigate whether EA may relieve inflammatory pain by suppressing the activation of spinal p38 MAPK in CFA-inflamed rats
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