The effect of intrathecal administration of cocaine and serotonergic antagonist (cyproheptadine) on nociception in rat

Background: Cocaine by effect on central nervous system inhibits reuptake of monoamines (serotonin, norepinephrine and dopamine) to presynaptic terminal and increases their concentration. Monoamines such as serotonin cause analgesia at the spinal level. This study investigates the effects of systemic and spinal administration of cocaine on pain sensation and the relation between these effects and serotonin. Materials and Methods: Male Wistar rats (200-250g) were set in groups: saline (i.p), saline/DMSO (i.p), cocaine 25mg/kg (i.p), saline (i.t.), saline/DMSO (i.t.), cocaine 100µg/10µl (i.t.), cyproheptadine 33µg/10µl (i.t.) and cyproheptadine 33µg/10µl/cocaine 100µg/10µl (i.t.). Tail flick latency was measured before and after administration. Intraplantar formalin was used for induction of chemical pain. The data was analyzed by T-Test and ANOVA. Results: Pain in both phases of formalin test was reduced in both cocaine 25mg/kg (i.p) (P<0.01) and cocaine 100µg/10µl (i.t.) (P<0.01). However, in cyproheptadine 33µg/10µl (i.t.), was increased in the first phase (P<0.01). In cyproheptadine 33µg/10µl/cocaine 100µg/10µl (i.t.), the part of pain reduction induced by cocaine was reversed, in both phases (P<0.01). In tail flick test the results of cyproheptadine 33µg/10µl (i.t.) showed reduced tail flick latency (P<0.001). Conclusions: Inhibition of serotonin reuptake at the spinal level plays role in analgesic effects of cocaine probably, because release of serotonin from the spinal serotonergic terminals causes inhibition of pain neurons and reduction of pain. In addition, inhibition of spinal serotonin receptors by cyproheptadine reduced part of analgesic effects of cocaine probably.