title: An early granulocyte colony-stimulating factor treatment attenuates neuropathic pain through activation of mu opioid receptors on the injured nerve.
abstract: Several studies have shown that the mu opioid receptor (MOR) located in the peripheral nerves can be activated after nerve injury and that it attenuates peripheral nociceptive signals to the spinal dorsal horn. Various cytokines and phosphorylated-p38 (p-p38) activation in the dorsal horn also play an important role in neuropathic pain development. Granulocyte-colony stimulating factor (GCSF) is a growth factor that can stimulate granulocyte formation and has been shown to exert an analgesic effect on neuropathic pain through recruiting opioid-containing leukocytes to the injured nerve. However, the underlying mechanisms are not well understood. Herein, the results of behavior tests in addition to MOR levels in the injured sciatic nerve and the levels of p-p38 and various cytokines in the spinal dorsal horn were studied in vehicle-treated or GCSF-treated chronic constriction injured (CCI) rats at different time points (i.e., 1, 3, and 7 days, respectively) after nerve injury. The results showed that a single early systemic GCSF treatment after nerve injury can up-regulate MORs in the injured nerve, which can decrease peripheral nociceptive signals. Thereafter, those changes suppress the pro-inflammatory cytokine IL-6 but enhance the anti-inflammatory cytokine IL-4, followed by decreases in p-p38 in the dorsal horn, and thus further attenuate neuropathic pain.
authors.affiliation: Department of Life Science, National Taiwan Normal University, 88, Ting-chou Rd., Sec. 4, Taipei, Taiwan.|Department of Neurology, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, 199, Tung Hwa North Rd., Taipei, Taiwan.
authors.forename: Ming-Feng
authors.initials: MF
authors.lastname: Liao
authors.affiliation: College of Life Science, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Shin-Rung
authors.initials: SR
authors.lastname: Yeh
authors.affiliation: Department of Neurology, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, 199, Tung Hwa North Rd., Taipei, Taiwan.
authors.forename: Ai-Lun
authors.initials: AL
authors.lastname: Lo
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Po-Kuan
authors.initials: PK
authors.lastname: Chao
authors.affiliation: Department of Neurology, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, 199, Tung Hwa North Rd., Taipei, Taiwan.
authors.forename: Yun-Lin
authors.initials: YL
authors.lastname: Lee
authors.affiliation: Department of Neurology, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, 199, Tung Hwa North Rd., Taipei, Taiwan.
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Hung
authors.affiliation: Department of Life Science, National Taiwan Normal University, 88, Ting-chou Rd., Sec. 4, Taipei, Taiwan.
authors.forename: Kwok-Tung
authors.initials: KT
authors.lastname: Lu
authors.affiliation: Department of Neurology, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, 199, Tung Hwa North Rd., Taipei, Taiwan.
authors.forename: Long-Sun
authors.initials: LS
authors.lastname: Ro
mesh_terms: D000818:Animals; D015415:Biomarkers; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D009437:Neuralgia / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D051381:Rats; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D012584:Sciatic Nerve / Q000293:injuries / Q000378:metabolism; D020426:Sciatic Neuropathy / Q000150:complications* / Q000209:etiology / Q000378:metabolism; D066148:Spinal Cord Dorsal Horn / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D017450:Receptors, Opioid, mu; D016179:Granulocyte Colony-Stimulating Factor; D048051:p38 Mitogen-Activated Protein Kinases