Electroacupuncture activates corticotrophin-releasing hormone-containing neurons in the paraventricular nucleus of the hypothalammus to alleviate edema in a rat model of inflammation.
BACKGROUND
Studies show that electroacupuncture (EA) has beneficial effects in patients with inflammatory diseases. This study investigated the mechanisms of EA anti-inflammation, using a rat model of complete Freund's adjuvant (CFA)-induced hind paw inflammation and hyperalgesia.


METHODS
Four experiments were conducted on male Sprague-Dawley rats (n = 6-7/per group). Inflammation was induced by injecting CFA into the plantar surface of one hind paw. Experiment 1 examined whether EA increases plasma adrenocorticotropic hormone (ACTH) levels. Experiments 2 and 3 studied the effects of the ACTH and corticotropin-releasing hormone (CRH) receptor antagonists, ACTH(11-24) and astressin, on the EA anti-edema. Experiment 4 determined whether EA activates CRH neurons in the paraventricular nucleus of the hypothalammus. EA treatment, 10 Hz at 3 mA and 0.1 ms pulse width, was given twice for 20 min each, once immediately post and again 2 hr post-CFA. Plasma ACTH levels, paw thickness, and paw withdrawal latency to a noxious thermal stimulus were measured 2 h and 5 h after the CFA.


RESULTS
EA significantly increased ACTH levels 5 h (2 folds) after CFA compared to sham EA control, but EA alone in naive rats and CFA alone did not induce significant increases in ACTH. ACTH(11-24) and astressin blocked EA anti-edema but not EA anti-hyperalgesia. EA induced phosphorylation of NR1, an essential subunit of the N-methyl-D-aspartic acid (NMDA) receptor, in CRH-containing neurons of the paraventricular nucleus.


CONCLUSIONS
The data demonstrate that EA activates CRH neurons to significantly increase plasma ACTH levels and suppress edema through CRH and ACTH receptors in a rat model of inflammation.
Li
Aihui
A
Center for Integrative Medicine, School of Medicine, University of Maryland, Baltimore, MD 21201, USA. ali002@umaryland.edu
Lao
Lixing
L
Wang
Yi
Y
Xin
Jiajia
J
Ren
Ke
K
Berman
Brian M
BM
Tan
Ming
M
Zhang
Ruixin
R
D000704:Analysis of Variance; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D004195:Disease Models, Animal; D004487:Edema / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control*; D015671:Electroacupuncture; D005620:Freund's Adjuvant; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000150:complications / Q000378:metabolism* / Q000628:therapy*; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D005620:Freund's Adjuvant; D003346:Corticotropin-Releasing Hormone