Spinal p38 activity and analgesic effect after low- and high-intensity electroacupuncture stimulation in a plantar incision rat model

• Published in: Life sciences (1973) 2015-05, Vol.128, p.15-23
• Main Authors: Hsu, Sheng-Feng, Zeng, Yen-Jing, Tsai, Shih-Ying, Chen, Kuen-Bao, Chen, Julia Yi-Ru, Chang, Ju-Hsin, Wen, Yeong-Ray
• Format: Article
• Language: English
• Subjects: Acupuncture Analgesia; Animals; Electroacupuncture; Electroacupuncture (EA); Hindlimb - pathology; Hyperalgesia - enzymology; Hyperalgesia - prevention & control; Imidazoles - administration & dosage; Injections, Spinal; Male; Microglia - enzymology; Nociceptive Pain - enzymology; Nociceptive Pain - prevention & control; p38 MAPK; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors; p38 Mitogen-Activated Protein Kinases - metabolism; Pain, Postoperative - enzymology; Pain, Postoperative - prevention & control; Phosphorylation; Postoperative pain; Protein Processing, Post-Translational; Pyridines - administration & dosage; Rats, Sprague-Dawley; Spinal cord; Spinal Cord - enzymology; Spinal Cord - pathology; Zusanli (ST36)
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2015.01.035

Postoperative pain is a major problem. Electroacupuncture (EA) has been accepted as a useful and low-risk complementary therapy for post-operative pain. Animal studies indicate that surgical incision activates p38 MAPK in the spinal microglia, which critically contributes to post-incisional nociceptive development. How EA affects incision-induced p38 activation is important but yet to be fully elucidated. Male adult rats received plantar incision (PI) at the right hind paw followed by 30-min EA of 4-Hz, one of two intensities (3 and 10mA), and at right ST36 (Zusanli) acupoint immediately after PI and for 3 successive days. EA analgesia was evaluated by von Frey fibers and Hargreaves' tests. Spinal p38 activation was examined by immunostaining. In separate groups, SB203580, a p38 inhibitor, was intrathecally injected alone or with EA to test the combining effect on nociception and spinal phospho-p38. EA of 10-mA significantly ameliorated mechanical allodynia, but 3-mA did not. None of them altered thermal hyperalgesia. Repeated EA could not inhibit phospho-p38 in the PI rats, contrarily, EA per se significantly induced phospho-p38 in the normal rats. Intrathecal SB203580 injection dose-dependently prevented PI-induced allodynia. Combination of low-dose SB203580 and 3-mA EA, which were ineffective individually, profoundly reduce post-PI allodynia. We demonstrated that 10-mA EA exerts a significant inhibition against post-PI mechanical hypersensitivity via a p38-independent pathway. Importantly, co-treatment with low-dose p38 inhibitor and 3-mA EA can counteract spinal phospho-p38 to exert strong analgesic effect. Our finding suggests a novel strategy to improve EA analgesic quality.