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

Abstract

AIMS:

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.

METHODS:

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.

KEY FINDINGS:

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.

SIGNIFICANCE:

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.

• Authors: Sheng-Feng Hsu, Yen-Jing Zeng, Shih-Ying Tsai, Kuen-Bao Chen, Julia Yi-Ru Chen, Ju-Hsin Chang, Yeong-Ray Wen
• Journal: Life sciences (Life Sci) Vol. 128 Pg. 15-23 (May 01 2015) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 25744405 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Imidazoles
• Pyridines
• p38 Mitogen-Activated Protein Kinases
• SB 203580

Topics

• Acupuncture Analgesia
• Animals
• Electroacupuncture
• Hindlimb (pathology)
• Hyperalgesia (enzymology, prevention & control)
• Imidazoles (administration & dosage)
• Injections, Spinal
• Male
• Microglia (enzymology)
• Nociceptive Pain (enzymology, prevention & control)
• Pain, Postoperative (enzymology, prevention & control)
• Phosphorylation
• Protein Processing, Post-Translational
• Pyridines (administration & dosage)
• Rats, Sprague-Dawley
• Spinal Cord (enzymology, pathology)
• p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)