The anti-inflammatory effects of low- and high-frequency electroacupuncture are mediated by peripheral opioids in a mouse air pouch inflammation model.
BACKGROUND
Although acupuncture has been widely used for complementary therapeutic approaches to treat inflammatory diseases and inflammation-induced pain, the potential anti-inflammatory effects of acupuncture treatment remain controversial in clinical trials, and the underlying mechanisms are still unclear.


OBJECTIVE
The objective was to determine whether electroacupuncture (EA) is able to suppress the peripheral inflammatory response (e.g., zymosan-induced leukocyte migration into air pouch). As part of a mechanistic approach, it was further evaluated whether endogenous opioid systems are involved in the "EA-induced anti-inflammatory effect" (EA-AI).


METHODS
EA (1 or 120 Hz) was performed bilaterally in the Zusanli acupoint (ST36) or in a nonacupoint (gluteal muscle) for 30 min in ICR mice under anesthetic condition. The number of leukocytes that migrated into the air pouch was counted 4 hours after zymosan injection. EA was performed at 0, 0.5, 1, or 2 hours prior to zymosan injection, respectively. To evaluate opioid involvement in EA-AI, intrathecal naloxone (36 microg/mouse) and intraperitoneal naloxone methiodide (30 mg/kg) were administered 10 min before EA stimulation.


RESULTS
Both the 1 and 120 Hz frequencies of EA into Zusanli acupoint at the same time with zymosan injection significantly reduced leukocyte migration into the air pouch as compared with those of control groups (i.e., anesthetic control and needling control into Zusanli acupoint without electrical stimulation). The EA stimulation into nonacupoint did not produce any significant anti-inflammatory effect. EA treatment at 0.5 hours prior to zymosan injection also produced an anti-inflammatory effect but 1 and 2 hours prior to zymosan injection did not elicit any effect. Peripheral opioid blockage significantly reversed EA-AI, whereas spinal opioid blockage did not alter EA-AI.


CONCLUSIONS
EA can suppress peripheral inflammation through a peripheral opioid mechanism. To achieve the full effectiveness of EA, repeated application is recommended for the treatment of a variety of inflammatory diseases.
Department of Veterinary Physiology, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
Hyun-Woo
HW
Kim
Dae-Hyun
DH
Roh
Seo-Yeon
SY
Yoon
Seuk-Yun
SY
Kang
Young-Bae
YB
Kwon
Ho-Jae
HJ
Han
Hye-Jung
HJ
Lee
Sun-Mi
SM
Choi
Yeon-Hee
YH
Ryu
Alvin J
AJ
Beitz
Jang-Hern
JH
Lee
D000704:Analysis of Variance; D000818:Animals; D015536:Down-Regulation; D004487:Edema / Q000139:chemically induced; D015671:Electroacupuncture / Q000379:methods*; D007249:Inflammation / Q000139:chemically induced / Q000628:therapy*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010146:Pain / Q000209:etiology / Q000517:prevention & control*; D011957:Receptors, Opioid / Q000378:metabolism / Q000528:radiation effects*; D015054:Zymosan / Q000633:toxicity
D011957:Receptors, Opioid; D015054:Zymosan