title: Electroacupuncture attenuates mechanical and warm allodynia through suppression of spinal glial activation in a rat model of neuropathic pain.
abstract: Neuropathic pain remains one of the most difficult clinical pain syndromes to treat. It is traditionally viewed as being mediated solely by neurons; however, glial cells have recently been implicated as powerful modulators of pain. It is known that the analgesic effects of electroacupuncture (EA) are mediated by descending pain inhibitory systems, which mainly involve spinal opioid, adrenergic, dopaminergic, serotonergic, and cholinergic receptors. However, studies investigating the suppressive effects of EA on spinal glial activation are rare. In the present study, we assessed the cumulative analgesic effects of EA on mechanical and warm allodynia in a rat model of neuropathic pain. We investigated the clinical efficacy of EA as long-term therapy and examined its effects on spinal glia, matrix metalloproteinase (MMP)-9/MMP-2, proinflammatory cytokines and serum immunoglobulin G (IgG) concentration. Rats were randomly divided into four groups as follows: the operation group (OP), operation with EA-non acupoint (EA-NA), operation with EA-ST36 acupoint (EA-ST36), and sham operation (shamOP). Following neuropathic or sham surgery, repeated EA was performed every other day after the behavioral test. On day 53 after the behavioral test, rats were perfused for immunohistochemistry and Western blot analysis to observe quantitative changes in spinal glial markers such as OX-42, astrocytic glial fibrillary acidic protein (GFAP), MMP-9/MMP-2, and proinflammatory cytokines. Allodynia and OX-42/GFAP/MMP-9/MMP-2/tumor necrosis factor (TNF)-α/interleukin (IL)-1β activity in the EA-ST36 group was significantly reduced, compared to the OP and EA-NA groups, and IgG in EA-ST36 rats significantly increased. Our results suggest that the analgesic effect of EA may be partly mediated via inhibition of inflammation and glial activation and repeated EA stimulation may be useful for treating chronic pain clinically.
authors.affiliation: Department of East-West Medicine, Graduate School, Kyung Hee University, Seoul, South Korea.
authors.forename: Gyeong-Taek
authors.initials: GT
authors.lastname: Gim
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Lee
authors.forename: Eunkuk
authors.initials: E
authors.lastname: Park
authors.forename: Yun-Hee
authors.initials: YH
authors.lastname: Sung
authors.forename: Chang-Ju
authors.initials: CJ
authors.lastname: Kim
authors.forename: Wei-Wan
authors.initials: WW
authors.lastname: Hwang
authors.forename: Jong-Phil
authors.initials: JP
authors.lastname: Chu
authors.forename: Byung-Il
authors.initials: BI
authors.lastname: Min
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015671:Electroacupuncture / Q000379:methods*; D006801:Humans; D006930:Hyperalgesia / Q000628:therapy*; D007074:Immunoglobulin G / Q000097:blood; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009437:Neuralgia / Q000503:physiopathology* / Q000628:therapy*; D009457:Neuroglia / Q000378:metabolism*; D010147:Pain Measurement; D010812:Physical Stimulation / Q000379:methods; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology*; D013696:Temperature; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D007074:Immunoglobulin G; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9