Effects of Intrathecal Carbenoxolone Treatment on Nociception and Analgesia in Rat

摘要

Background: Gap junctions (GJ) are important in pain signalling at the spinal cord level. Aims: The aim of this investigation was to study the effects of GJ on nociception and the analgesic/hyperalgesic effects of mor-phine following administration of carbenoxolone as a GJ blocker. Male Wistar rats (200-250 g) were divided into three groups: saline i.p., 10 mg/kg and 1 μg/kg i.p. morphine, each with two subgroups. One was treated intrathecally with saline and the other with carben-oxolone. Study Design: Animal experiment. Methods: The thermal nociception threshold was measured prior to and after injections using the tail flick test. Chemical nociception assessment was conducted using a 0.05-mL subplantar injection of 2.5% formalin. Results: Both formalin-induced neurogenic and inflammatory nociception were reduced in the [saline i.p./carbenoxolone i.t.] and [morphine 1 μg/kg, i.p./carbenoxolone i.t.] subgroups (p<0.001). The 10 mg/kg i.p. morphine, i.t./carbenoxolone treatment reduced morphine-induced analgesia in the inflammatory phase (p<0.05), while it was ineffective in the neurogenic phase. Carbenoxolone decreased 1 μg/kg i.p. morphine-induced hyperalgesia in the tail flick test (p<0.001). Conclusion: Based on the results, GJ probably play a role in nociception at the spinal cord level. This may be due to the facilitation of inflammatory mediators released from glial cells or the connection between stimulatory interneurons and projection neurons. GJ blocking attenuated morphine-induced analgesia. This may be due to the attenuation of pre/post-synaptic inhibitory effects of morphine at the spinal cord level. As demonstrated by the investigations, GJ are present between inhibitory interneurons. Therefore, we can assume that blockage of GJ between inhibitory interneurons will reduce morphine-induced analgesia at the spinal cord level. However, this requires further investigation.