【摘 要】
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Neuropathic pain is a chronic debilitating symptom characterized by spontaneous pain and mechanical allodynia.It occurs in distinct forms,including brushevoked dynamic and filament-evoked punctate mechanical allodynia.Potassium channel 2.1 (Kir2.1),which
【机 构】
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Department of Neurology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiolog
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Neuropathic pain is a chronic debilitating symptom characterized by spontaneous pain and mechanical allodynia.It occurs in distinct forms,including brushevoked dynamic and filament-evoked punctate mechanical allodynia.Potassium channel 2.1 (Kir2.1),which exhibits strong inward rectification,is and regulates the activity of lamina I projection neurons.However,the relationship between Kir2.1 channels and mechanical allodynia is still unclear.In this study,we first found that pretreatment with ML133,a selective Kir2.1 inhibitor,by intrathecal administration,preferentially inhibited dynamic,but not punctate,allodynia in mice with spared nerve injury (SNI).Intrathecal injection of low doses of strychnine,a glycine receptor inhibitor,selectively induced dynamic,but not punctate allodynia,not only in na(i)ve but also in ML133-pretreated mice.In contrast,bicuculline,a GABAA receptor antagonist,induced only punctate,but not dynamic,allodynia.These results indicated the involvement of glycinergic transmission in the development of dynamic allodynia.We further found that SNI significantly suppressed the frequency,but not the amplitude,of the glycinergic spontaneous inhibitory postsynaptic currents (gly-sIPSCs) in neurons on the lamina Ⅱ-Ⅲ border of the spinal dorsal horn,and pretreatment with ML133 prevented the SNI-induced gly-sIPSC reduction.Furthermore,5 days after SNI,ML133,either by intrathecal administration or acute bath perfusion,and strychnine sensitively reversed the SNI-induced dynamic,but not punctate,allodynia and the gly-sIPSC reduction in lamina IIi neurons,respectively.In conclusion,our results suggest that blockade of Kir2.1 channels in the spinal dorsal horn selectively inhibits dynamic,but not punctate,mechanical allodynia by enhancing glycinergic inhibitory transmission.
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