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Anti‐inflammatory and anti‐hyperalgesia activities of KMUP‐1 in a rat chronic constriction injury model
Author(s) -
Wu BinNan,
Lin TingChun,
Chia SooLin
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb565
Subject(s) - neuropathic pain , sciatic nerve , medicine , hyperalgesia , proinflammatory cytokine , pharmacology , anesthesia , allodynia , inflammation , nociception , immunology , receptor
Neuropathic pain is characterized by spontaneous pain, hyperalgesia and allodynia. Pharmacological interventions have had limited success so far. In this study, we investigate whether KMUP‐1 could improve pain hypersensitivity and reduce inflammatory mediators, and also explore the possible mechanisms in rats’ sciatic nerve with chronic constriction injury (CCI) to induce neuropathic pain. Sprague–Dawley rats were divided into four groups, including sham, sham+KMUP‐1, CCI and CCI+KMUP‐1. KMUP‐1 (5 mg/kg, i.p.) was injected once daily starting at day 1 after surgery. Mechanical and thermal responses were assessed before surgery and at day 3, 7, 14 after CCI. Thermal hyperalgesia and mechanical allodynia were reduced in CCI+KMUP‐1 compared with CCI group. Sciatic nerves were isolated for western blots and enzyme‐linked immunosorbent assay to analyze proteins and cytokines levels. Inflammatory proteins (COX2, iNOS, nNOS) and proinflammatory mediators (IL‐1β, TNF‐α) induced by CCI were decreased in KMUP‐1‐treated group at day 7 after surgery. KMUP‐1 also inhibited neuropathic pain‐related mechanisms, including p38 and ERK activation, but not JNK, which are members of MAPKs. KMUP‐1 also blocked IκBα phosphorylation and NF‐κB translocation to nuclei. We suggest that KMUP‐1 has anti‐inflammatory and anti‐hyperalgesia properties in CCI‐induced neuropathic pain via inhibition of MAPK and NF‐κB.