| Summary: | 碩士 === 高雄醫學大學 === 藥理學研究所 === 100 === Neuropathic pain is a deleterious change to the sensory transmission pathway after a lesion or dysfunction of the nervous system. Peripheral neuropathic pain is characterized by spontaneous pain, hyperalgesia and allodynia. It adversely affects quality of life, reduces physical and emotional functioning.
Previous studies have been shown that peripheral nerve injury could induce inflammatory states, resulting in the genesis and maintenance of neuropathic pain. Phrmacological interventions have been tried in experimental models and in clinical trials but unfortunately have met with limited success. In the present study, we tried to investigate whether KMUP-1 could improve pain hypersensitivity and reduce the production of inflammatory mediators, and also explore the possible underlying mechanism in sciatic nerve in rats with chronic constriction injury (CCI) to induce neuropathic pain.
Sprague–Dawley (SD) rats were randomly divided into four groups, including sham, sham with KMUP-1, chronic constriction injury (CCI) of bilateral sciatic nerve and CCI with KMUP-1 group. Rats were subjected to CCI surgery, KMUP-1 (5 mg/kg) was administrated intraperitoneally once daily starting at 1 day after surgery. Both mechanical and thermal responses of both hind paws were assessed before surgery and at day 3, 7, 14 after sciatic nerve injury.
Behavioral monitoring, including thermal hyperalgesia and mechanical allodynia were both significantly reduced in CCI treated with KMUP-1 group compared with CCI group. Sciatic nerves were isolated from the four groups for western blots and enzyme-linked immunosorbent assay (ELISA) to analyze proteins and cytokines level, respectively. We found that the protein expressions of inflammatory mediators (COX2, iNOS, nNOS) and proinflammatory mediators (IL-1β, TNF-α) induced by CCI were significantly decreased in KMUP-1-treated group at day 7 after surgery. Additionally, KMUP-1 inhibited neuropathic pain-related mechanisms, including p38 and ERK activation, but not JNK, which are members of mitogen-activated protein kinases (MAPKs). KMUP-1 also blocked CCI-induced inhibitor κBα (IκBα) phosphorylation and nuclear factor-kappa B (NF-κB) translocation to nuclear.
In conclusion, the results suggest that KMUP-1 has anti- inflammatory and anti-pain hypersensitivity properties in CCI-induced neuropathic pain through inhibition of MAPK and NF-κB activation. Therefore, KMUP-1 might be a potential agent for the control of neuropathic pain.
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