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


RESULTS
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.


CONCLUSIONS
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.
Graduate Institute of Acupuncture Science, College of Chinese Medicine, China Medical University, Taichung, Taiwan; Department of Acupuncture, China Medical University Hospital Taipei Branch, Taipei, Taiwan.
Sheng-Feng
SF
Hsu
Graduate Institute of Acupuncture Science, College of Chinese Medicine, China Medical University, Taichung, Taiwan; Graduate Institute of Clinical Medical Science, College of Medicine, China Medical University, Taichung, Taiwan.
Yen-Jing
YJ
Zeng
Department of Anesthesiology, School of Medicine, China Medical University, Taichung, Taiwan.
Shih-Ying
SY
Tsai
Department of Anesthesiology, China Medical University Hospital, Taichung, Taiwan.
Kuen-Bao
KB
Chen
Department of Pediatrics, School of Medicine, Taipei Medical University, Taipei, Taiwan; Guang Li Biomedicine, Inc., Xizhi, New Taipei City, Taiwan.
Julia Yi-Ru
JY
Chen
Graduate Institute of Clinical Medical Science, College of Medicine, China Medical University, Taichung, Taiwan; Department of Anesthesiology, China Medical University Hospital, Taichung, Taiwan.
Ju-Hsin
JH
Chang
Department of Anesthesiology, School of Medicine, China Medical University, Taichung, Taiwan; Department of Anesthesiology, China Medical University Hospital, Taichung, Taiwan; Research Center for Chinese Medicine and Acupuncturex, School of Medicine, Taiwan. Electronic address: yr.wen@yahoo.com.tw.
Yeong-Ray
YR
Wen
D015667:Acupuncture Analgesia; D000818:Animals; D015671:Electroacupuncture; D006614:Hindlimb / Q000473:pathology; D006930:Hyperalgesia / Q000201:enzymology / Q000517:prevention & control; D007093:Imidazoles / Q000008:administration & dosage; D007278:Injections, Spinal; D008297:Male; D017628:Microglia / Q000201:enzymology; D059226:Nociceptive Pain / Q000201:enzymology / Q000517:prevention & control*; D010149:Postoperative Pain / Q000201:enzymology / Q000517:prevention & control*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011725:Pyridines / Q000008:administration & dosage; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000201:enzymology / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D007093:Imidazoles; D011725:Pyridines; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580
Electroacupuncture (EA); Postoperative pain; Spinal cord; Zusanli (ST36); p38 MAPK