Characterizations of descending 5-HTergic inhibitory systems determined by spinal microdialysis

Background: Although the derangement of assending nociceptive transmission in spinal cord including neuroplasticity have been investigated, the role of serotoninergic (5-HT) descending inhibitory system originated from rostro-ventral medulla remained unclear. Recently, the ability of selective 5-HT reuptake inhibitor (SSRI), is focusing for modulating effects of spinal nociceptive transmission in both spinal and supraspinal cord. But, its mechanism is still remained unclear. Therefore, we characterized the effects of SSRI on spinal nociceptive transmission of 5-HT by using spinal microdialysis in relation to pain behavior after mustered oil (MO) paw injection in rats. Methods: The rats implanted with intrathecal microdialysis probe along with PE-10 tube was subjected for injecting mustered oil into paw. The major metabolite of 5-HT, 5-HIAA, in CSF (HPLC-ECD) level and flinchings were periodically measured following MO injection. SSRI (ip.), 5-HT (it.), morphine (it.), or pentobarbital (ip.) was given before injecting MO. Results: After that, the flinchings were gradually increased accompanied by slight increase of CSF-5-HIAA level. With SSRI, rats showed significant reduction of flinching after MO injection without change in CSF-5-HIAA level. But, there were remarkable increases in CSF-5-HIAA levels with 5-HT it. The significant reduction of flinching by morphine was associated with considerable decrease in CSF-5-HIAA. Pentobarbital produced satisfactory sedation, but no analgesic effect associated with any change in CSF-5-HIAA level. Conclusion: Based on the present study, when peripheral stimulation arrives to the brain through spinal cord, the sensory-limbic systems networks in brain evoke 5-HT or noradrenaline contained descending inhibitory system to block ascending nociceptive information. We demonstrated that SSRI has beneficial effects of analgesia without changes in 5-HT release observed by using spinal microdialysis. According to changes in CSF-5-HIAA levels, SSRI induced analgesia may be concerned with mechanisms underlying 1) inhibition of presynaptic neurons of c-fiver by activating 5-HT1 receptor, and 2) stimulation of the enkephaline contained inter-neurons by activating 5-HT2 receptor. The use of SSRI is expected as potential drug for management of patients with cancer, neuropathic pain, and any other chronic painful diseases.