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

Sheng Feng Hsu, Yen Jing Zeng, Shih Ying Tsai, Kuen Bao Chen, Julia Yi Ru Chen, Ju Hsin Chang, Yeong Ray Wen

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


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 10 mA), 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.

Original languageEnglish
Article number14297
Pages (from-to)15-23
Number of pages9
JournalLife Sciences
Publication statusPublished - May 1 2015
Externally publishedYes


  • Electroacupuncture (EA)
  • p38 MAPK
  • Postoperative pain
  • Spinal cord
  • Zusanli (ST36)

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • General Biochemistry,Genetics and Molecular Biology
  • General Medicine


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