| Summary: | 碩士 === 高雄醫學大學 === 醫學系藥理學科研究所 === 102 === Neuropathic pain is a common chronic pain. Such pain may result from lesions to the peripheral or central nervous systems. This chronic pain is usually persistent or recurrent. Patient with this pain usually have dysesthesia, such as hyperalgesia and allodynia.
Many pharmacological interventions have been tried in experimental models and in clinical trials but unfortunately have met with limited success. In previous studies have shown that peripheral nerve injury could change some ion channels expression, such as large-conductance Ca2+-activated K+ (BKCa) channels. Many studies showed that nerve injury suppresses BKCa expression and activity in dorsal root ganglion (DRG) neurons. A xanthine derivative KMUP-1 has been demonstrated to activate BKCa currents in smooth muscle myocytes. Therefore, we attempt to investigate whether KMUP-1 could alleviate chronic constriction injury (CCI)-induced neuropathic pain and BKCa currents inhibition in DRG neurons.
Sprague–Dawley rats were randomly divided into four groups: sham, sham with KMUP-1, CCI and CCI with KMUP-1. Each treatment group was administrated with KMUP-1 (5 mg/kg i.p.) once daily starting at 1 day after surgery. Each group was sacrificed at day 7 and L4-L6 DRGs removed quickly for isolation experiment.
For electrophysiological studies, DRG neurons were dispersed into single cells by collagenase and cultured on 12-mm coverslip for 2 days. Using whole-cell patch-clamp techniques, the paxilline-sensitive BKCa currents attenuated in CCI groups compared with control have been decreased and this effect was prevented by KMUP-1-treated group. In current clamp experiments, CCI-induced DRG neurons prolonged the action potential compared with the sham group. In cell-attached recordings, CCI-induced nerve injury neurons decreased BKCa channel activity. Immunohistochemistry staining further demonstrated that CCI-induced nerve injury reduced the expression of BKCa channels, and the effects also improved by KMUP-1-treated group.
KMUP-1 prevents CCI-induced neuropathic pain and BKCa currents inhibition in peripheral nerve injury model. In summary, we suggest that KMUP-1 could be a potential agent for the control of neuropathic pain.
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