title: Electroacupuncture attenuates bone-cancer-induced hyperalgesia and inhibits spinal preprodynorphin expression in a rat model.
abstract: Cancer pain impairs the quality of life of cancer patients, but opioid intervention can cause significant side effects that further decrease quality of life. Although electroacupuncture (EA) has been used to treat cancer pain, its mechanisms are largely unknown. To examine its effects and underlying mechanisms on cancer pain, we injected AT-3.1 prostate cancer cells into the tibia to induce bone cancer in the male Copenhagen rat. The resulting pain was treated with 10Hz/2mA/0.4ms pulse EA for 30min daily at the point equivalent to the human acupoint GB30 (Huantiao) between days 14 and 18 after the injection. For sham control, EA needles were inserted into GB30 without stimulation. Thermal hyperalgesia, a decrease in paw withdrawal latency (PWL) to a noxious thermal stimulus, and mechanical hyperalgesia, a decrease in paw withdrawal pressure threshold (PWPT), was measured at baseline and 20min after the EA treatment. Preprodynorphin mRNA and dynorphin were determined by RT-PCR and immunohistochemistry, respectively. Thermal and mechanical hyperalgesia developed ipsilaterally between days 12 and 18 after cancer cell inoculation. EA significantly (P<0.05) attenuated this hyperalgesia, as shown by increased PWL and PWPT, and inhibited up-regulation of preprodynorphin mRNA and dynorphin compared to sham control. Intrathecal injection of antiserum against dynorphin A (1-17) also significantly inhibited the cancer-induced hyperalgesia. These results suggest that EA alleviates bone cancer pain at least in part by suppressing dynorphin expression, and they support the clinical use of EA in the treatment of cancer pain.
authors.affiliation: Center For Integrative Medicine, School of Medicine, University of Maryland, HSF-2, Room S209, 20 Penn Street, Baltimore, MD 21201, USA. Rzhan001@umaryland.edu
authors.forename: Rui-Xin
authors.initials: RX
authors.lastname: Zhang
authors.forename: Aihui
authors.initials: A
authors.lastname: Li
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.forename: Linbo
authors.initials: L
authors.lastname: Wang
authors.forename: Jiajia
authors.initials: J
authors.lastname: Xin
authors.forename: Ke
authors.initials: K
authors.lastname: Ren
authors.forename: Jian-Tian
authors.initials: JT
authors.lastname: Qiao
authors.forename: Brian M
authors.initials: BM
authors.lastname: Berman
authors.forename: Lixing
authors.initials: L
authors.lastname: Lao
mesh_terms: D015667:Acupuncture Analgesia; D000230:Adenocarcinoma / Q000503:physiopathology / Q000556:secondary*; D000818:Animals; D001859:Bone Neoplasms / Q000503:physiopathology / Q000556:secondary*; D045744:Cell Line, Tumor / Q000637:transplantation; D015536:Down-Regulation; D004399:Dynorphins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015671:Electroacupuncture; D006930:Hyperalgesia / Q000209:etiology / Q000628:therapy*; D007106:Immune Sera; D007116:Immunization, Passive; D007278:Injections, Spinal; D008297:Male; D017288:Pain Threshold; D011498:Protein Precursors / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D011930:Reaction Time; D013116:Spinal Cord / Q000378:metabolism*; D013977:Tibia
chemical_list: D007106:Immune Sera; D011498:Protein Precursors; C036448:pre-prodynorphin; D004399:Dynorphins