Abstract:

 Objective To evaluate the analgesic action of intrathecal injection of KB-R7943 in SNL rats, and explore the possible mechanism of analgesia. Methods Male Sprague-Dawley rats（180-220 g）were randomly assigned to four groups, treated with a subarachnoid catheter and subjected to SNL surgery. On day 7 after surgery, the groups received intrathecal injection of solvent or KB-R7943 in doses of 5，10 or 20 μg. Behavioral tests were used to detect changes in mechanical pain threshold and thermal pain threshold. In addition, expression of the sodium-calcium exchanger protein （NCX） on the operation side of the L4-6 spinal dorsal horn was measured using immunofluorescence, and spinal dorsal horn C fiber-evoked potentials were measured. Tetanic stimulation was used to induce long-term potentiation of the C fiber, and changes in C fiber potential amplitude were recorded after applying KB-R7943 or control solvent to the surface of the local spinal cord. Results NCX was expressed on the C fiber projection area of the L4-6 spinal dorsal horn. Intrathecal injection of NCX inhibitor KB-R7943 significantly increased the threshold of mechanical and thermal pain（P<0.05），and these effects positively correlated with KB-R7943 dose. KB-R7943 also reduced the potential amplitude of the C fiber observed after tetanic stimulation. Conclusions Intrathecal injection of KB-R7943 produces a dose-dependent analgesic effect in SNL rats. This effect may involve inhibition of the reverse transfer function of NCX in the spinal dorsal horn, as well as reduction in long-term potentiation of C fiber-evoked potential in the spinal dorsal horn.

Key words: Neuropathy pain, Cancer pain, KB-R7943, Sodium-calcium exchange protein(NCX) , Intrathecal injection, Long-term potentiation