Role Of ATP-sensitive Potassium Channel In Allodynia Of Rat Bone Cancer Pain

Objective:1.Observe the changes of pain thresholds of bone cancer pain model rats after intrathecal injection with pinacidil (a KATP channel opener) or glybenclamide (a blocker of KATP channel). Explore the roles of opener and blocker of KATP channel in allodynia of bone cancer pain.2.The specific siRNA (aimed at Kir6.2 mRNA) is applied to inhibit the expression of KATP channels in rats spinal dorsal horn neurons, and observe changes of rats pain thresholds. Investigate effect of KATP channels expression level on bone cancer pain.Methods:1.Rat models of bone cancer pain were established by implanting the rat mammary gland carcinoma cells Walker256 into rat tibial intramedullary space. The changes of rats mechanical withdrawal thresholds (MWTs) were measured, which were given different interventions beforehand, e.g. intrathecal injection of DMSO, artificial cerebrospinal fluid (aCSF), pinacidil (a KATP channel opener), or glybenclamide (a blocker of KATP channel).2.Chitosan-siRNA nanoparticles were prepared by the ionic gelation technique. The changes of rats MWTs were observed after intrathecal administration of the specific siRNA or the mismatch siRNA. And the relative quantity of Kir6.2 mRNA in each group was measured by real-time quantitative PCR.Results:1.MWTs of Rats decreased after implanting Walker256 cells into the tibia. MWTs of model rats increased after intrathecal injection of pinacidil in a dose-dependent way. While glybenclamide decreased MWTs of model rats in a dose-dependent manner. However, DMSO and aCSF have no significant effects on MWTs of model rats.2.MWTs of normal rats decreased after intrathecal delivery of the specific siRNA. And the specific siRNA down-regulated the expression of Kir6.2 mRNA in normal rats spinal cord. MWTs of model rats also decreased after intrathecal administration of the specific siRNA. And the expression of Kir6.2 mRNA in model rats spinal cord was down-regulated by the specific siRNA. However, both MWTs and expression level of Kir6.2 gene were not influenced by the mismatch siRNA in the normal and model rats. Furthermore the expression of Kir6.2 gene in spinal cord of model rats was less than that in normal rats.Conclusions:Pain thresholds of bone cancer pain model rats were significantly affected by both functional states and expression level of KATP channels in spinal dorsal horn, which indicated KATP channels in dorsal horn neurons played an important role in allodynia of rat bone cancer pain.