ABSTRACT
ObjectiveTo observe the changes in the expression and distribution of G protein-gated inwardly rectifying potassium channel subunit 2 （GIRK2） in the dorsal root ganglion （DRG） and spinal cord dorsal horn of rats with remifentanil-induced hyperalgesia. MethodsHyperalgesia was induced by intravenous infusion of remifentanil 4 μg/kg/min for 2 h in adult male SD rats. At 6th hour and on days 1， 3 and 5 following remifentanil treatment， we used immunofluorescence to examine the changes in the GIRK2 distribution and expression. Immunoblotting was used to detect GIRK2 expression of the total protein and membrane protein in DRG and spinal dorsal horn of rats. Behavioral testing was applied to evaluate the effect of intrathecal injection of GIRK2-specific agonist ML297 on thermal nociceptive threshold on day 1 after remifentanil infusion. Resultsmmunofluorescence results showed that GIRK2 was mainly co-localized with IB4-positive small neurons in DRG and nerve fibers in spinal dorsal horn. GIRK2 expression was significantly downregulated following remifentanil treatment. Immunoblotting results revealed that on day 1 following intravenous infusion of remifentanil， compared with those in the control group， GIRK2 expression levels of the total protein and membrane protein in DRG （0.47 ± 0.10 vs. 1.01 ± 0.17， P < 0.001； 0.47 ± 0.11 vs. 1.06 ± 0.12， P < 0.001） and spinal dorsal horn （0.52 ± 0.09 vs. 1.10 ± 0.08， P < 0.001； 0.54 ± 0.10 vs. 1.01 ± 0.13， P < 0.001） were all significantly decreased. The behavioral results showed that intrathecal ML297 effect on thermal withdrawal latency was significantly reduced following remifentanil treatment （P < 0.001）. ConclusionsRemifentanil might induce hyperalgesia via down-regulating GIRK2 expression in rat DRG and spinal cord dorsal horn.