Low-frequency electroacupuncture suppresses zymosan-induced peripheral inflammation via activation of sympathetic post-ganglionic neurons.
Electroacupuncture (EA) is used to treat a variety of inflammatory diseases; however, the neurophysiological mechanisms underlying EA's anti-inflammatory effect remain unclear. Accumulating evidence suggests that the sympathetic nervous system regulates immunologic and inflammatory responses and thus we hypothesized that this system could be involved in EA's anti-inflammatory effect (EA-AI). The goal of the present study was to evaluate whether the sympathetic nervous system plays a critical role in EA-AI using a mouse air pouch inflammation model. We found that bilateral low-frequency (1 Hz) EA applied to the Zusanli acupoint significantly suppressed the number of zymosan-induced leukocytes migrating into the air pouch. Furthermore, double-labeling immunohistochemical experiments showed that EA stimulation increased Fos expression in choline acetyltransferase (ChAT)-positive sympathetic pre-ganglionic neurons in the intermediolateral region of thoracic spinal cord segments. Chemical sympathetic denervation by intraperitoneal injection of 6-hydroxydopamine (which spares sympathetic adrenal medullary innervation) significantly inhibited EA-AI. In contrast, adrenalectomy did not alter EA-AI. Finally, systemic propranolol administration significantly inhibited EA's anti-inflammatory effect, suggesting that beta-adrenoceptors are involved. Collectively, these results suggest that EA produces an anti-inflammatory effect in this mouse air pouch model by activating the sympathetic nervous system leading to the release of catecholamines from post-ganglionic nerve terminals, which act on beta-adrenoceptors on immune cells to inhibit their migration.
Kim
Hyun-Woo
HW
Department of Veterinary Physiology, College of Veterinary Medicine and BK21 Program for Veterinary Science, Seoul National University, Seoul, South Korea.
Kang
Suk-Yun
SY
Yoon
Seo-Yeon
SY
Roh
Dae-Hyun
DH
Kwon
Young-Bae
YB
Han
Ho-Jae
HJ
Lee
Hye-Jung
HJ
Beitz
Alvin J
AJ
Lee
Jang-Hern
JH
D000110:Acetylcholinesterase / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D015671:Electroacupuncture / Q000379:methods* / Q000592:standards; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology* / Q000628:therapy*; D018836:Inflammation Mediators / Q000009:adverse effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000294:innervation* / Q000503:physiopathology*; D013116:Spinal Cord / Q000378:metabolism; D013563:Sympathectomy, Chemical / Q000379:methods; D017779:Sympathetic Fibers, Postganglionic / Q000378:metabolism*; D015054:Zymosan / Q000009:adverse effects
D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D018836:Inflammation Mediators; D015054:Zymosan; D000110:Acetylcholinesterase