early systemic granulocyte-colony stimulating factor treatment attenuates neuropathic pain after peripheral nerve injury早期系统性粒细胞集落刺激因子治疗周围神经损伤后减弱神经性疼痛.pdfVIP

Early Systemic Granulocyte-Colony Stimulating Factor Treatment Attenuates Neuropathic Pain after Peripheral Nerve Injury Po-Kuan Chao1., Kwok-Tung Lu 1., Yun-Lin Lee2, Jin-Chung Chen3, Hung-Li Wang4, Yi-Ling Yang5, Mei- Yun Cheng2, Ming-Feng Liao2, Long-Sun Ro2* 1 Department of Life Science, National Taiwan Normal University, Taipei, Taiwan, 2 Division of Neuromuscular Disorders, Department of Neurology, Chang Gung Memorial Hospital and University, Chang-Gung University, Tao-Yuan, Taiwan, 3 Department of Pharmacology, Chang-Gung University, Tao-Yuan, Taiwan, 4 Department of Physiology, Chang-Gung University, Tao-Yuan, Taiwan, 5 Institute of Biotechnology, National Chia-Yi University, Chia-Yi, Taiwan Abstract Recent studies have shown that opioid treatment can reduce pro-inflammatory cytokine production and counteract various neuropathic pain syndromes. Granulocyte colony-stimulating factor (G-CSF) can promote immune cell differentiation by increasing leukocytes (mainly opioid-containing polymorphonuclear (PMN) cells), suggesting a potential beneficial role in treating chronic pain. This study shows the effectiveness of exogenous G-CSF treatment (200 mg/kg) for alleviating thermal hyperalgesia and mechanical allodynia in rats with chronic constriction injury (CCI), during post-operative days 1–25, compared to that of vehicle treatment. G-CSF also increases the recruitment of opioid-containing PMN cells into the injured nerve. After CCI, single administration of G-CSF on days 0, 1, and 2, but not on day 3, relieved thermal hyperalgesia, which indicated that its effect on neuropathic pain had a therapeutic window of 0–48 h after nerve injury. CCI led to an increase in the levels of interleukin-6 (IL-6) mRNA and tumor necrosis factor-a (TNF-a) protein in the dorsal root ganglia (DRG). These high