KMUP-1 Ameliorates Neuropathic Pain via Inhibition of ERK and NF-κB Pathways in the Dorsal Horn of Spinal Cord

• Main Authors: Wun-Ching Hsu, 許雯晴
• Other Authors: Bin-Nan Wu
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/99412672606693910664

碩士 === 高雄醫學大學 === 藥理學研究所 === 101 === Neuropathic pain occurs as a result of injury to the sensory transmission after a primary lesion or dysfunction in the nervous system. Peripheral nerve injury may produce chronic pain states characterized by hyperalgesia, allodynia and spontaneous pain. Patients with neuropathic pain have higher pain scores and lower quality of life than other chronic pain patients. Chronic pain is categorized into inflammatory pain, induced by peripheral tissue inflammation, and causes damage and malfunction of the nerve system. Many reports have been shown that peripheral nerve injury could induce inflammatory states, resulting in the genesis and maintenance of neuropathic pain. Despite the large number of approved analgesic drugs, effective treatment of chronic pain is still unsatisfactory because of the severe side effects from these drugs. In the present study, we tried to investigate whether KMUP-1 could attenuate pain hypersensitivity and inflammatory mediators, and to explore its possible mechanisms in the dorsal horn of spinal cord of rats after chronic constriction injury-induced neuropathic pain. Male SD rats were randomly assigned to four groups: sham, sham plus KMUP-1, chronic constriction injury (CCI) of bilateral sciatic nerve and CCI plus KMUP-1 groups. After the CCI model was established, KMUP-1 (5 mg/kg) was administrated intraperitoneally once daily for 3, 7 and 14 days. Measurements of mechanical withdrawal threshoulds using von Frey filaments and thermal withdrawal latency using radiant heat applied to the plantar surface, were made daily before and after the injection of each dose. CCI of the sciatic nerve induced mechanical allodynia and thermal hyperalgesia and this effect was accompanied by increased levels of inflammatory mediators. The dorsal horn of spinal cord was divided into ipsilateral and contralateral parts for western blots and enzyme-linked immunosorbent assay to analyze the levels of inflammatory proteins and cytokines, respectively. We demonstrated that chronic intraperitoneally KMUP-1 has beneficial effects on the behaviors of both thermal and mechanical stimulations in the neuropathic pain animals. Furthermore, KMUP-1 reduced the expression of inflammatory protein and cytokines in the spinal dorsal horn on Day 3, 7, 14 for the model rats of CCI. In conclusion, KMUP-1 has anti-inflammatory and anti-pain hypersensitivity properties through inhibition of ERK and NF-κB activation in the development of pain hypersensitivity after nerve injury. Therefore, KMUP-1 could be a potential pharmacotherapeutic agent for the treatment of neuropathic pain.