The Modulation Role And Mechanism Of Oxytocin In Incisional Pain In Rats

To investigate the variation regularity of oxytocin in central nervoussystem in rats after hind paw incision. Intraperitoneal,intrathecal and intracerebralventricular injection of oxytocin were administered to evaluate the pain modulation role, then we applied atosiban or naloxone preliminarily to inhibit the oxytocin receptor and opipoid receptor respectively to establish the fundmental mechanism.. Methods:1. Male SD rats were divided randomly into2groups, the blankgroup and the incisional group which was established according to Brennan (1996). The number of OT-positve cells in PVN and lumbar spinal cord was counted on timepoint of30min,1h,3h,6h and24h after incision and the blank group rats. We used western-blot and RT-PCR to detect the transcription and expression of OT and OTR in PVN and lumbar spinal cord.2.Male SD rats were divided randomly into3groups:theintraperitoneal(i.p) group,the intrathecal(i.th) group and the intracerebralventricular(i.c.v) group.The intraperitoneal group was divided into4subgroups, the100μl normal saline,0.5nmolOT,1nmol OT and2.5nmol OT group, then the mechanical hypersensitivity was assessed30min,1h,3h,6h,12h,24h after incision. Also the threshold of10min,30min,1h,3h,6h,12h,24h after incision was measured in normal saline,0.05nmol,0.1nmol and0.25nmol groups in i.th and i.c.v rats. 3. Male SD rats were divided randomly into2groups,i.th group and i.c.v group. And both groups divided into9subgroups below,①N.S+OT0.05nmol;②N.S+OT0.1nmol;③N.S+OT0.25nmol;④atosiban1.0nmol+OT0.05nmol;⑤atosiban1.0nmol+OT0.1nmol;⑥atosiban1.0nmol+OT0.25nmol;⑦naloxone0.5μg+OT0.05nmol;⑧naloxone0.5μg+OT0.1nmol and⑨naloxone0.5μg+OT0.25nmolg group. And the mechanical threshold was tested10min,30min,1h,3h,6h,12h,24h after incision in all the rats.Results:1. The decrease of OT-positive cells in PVN of incisional rats lasts from30min to at least6h after operation compared to the blank control, and the western-blot reassure that tendency, however the mRNA increases from30min to1h; The reverse changes were detected in the spinal cord, where the OT-positive cells increased from30min to6h without any transcription. The expression of OTR was negative in PNV but elevated in the I-II layer of lumbar spinal cord from30min to12h after incision.2. Intrathecal administration of0.5nmol,1nmol or2.5nmol OT has no effect on incisional pain in rats. But intrathecal and intracerebralventricular OT (0.05nmol,0.1nmol or0.25nmol) can dose dependently alleviate the mechanical hypersensitivity from10min to6h, and that has a ceiling effect.3. I.th and i.c.v administration of atosiban (an oxytocin receptor antagnist) can thoroughly inhibit the analgesia effect of OT even the dose of OT increased; however naloxone applied intrathecally or intracerebralventricularly can only inhibit such function of OT partly, and the analgesia appeared again when the dose increased to0.25nmol.Conclusions: 1. The transcription of OT in PVN in incisional pain rats increased but the expression decreased, however in spinal cord the expression increased without any OT transcription, it indicates that the increased OT in PVN is transmited to spinal cord or other sites in central nervers system after incision to play modulation role.2. The OTR was negative in both incisional and normal rats, but the increased expression was detected in the superficial layer of lumbar intumescentia. It suggests the modulation role of OT is more important in spinal cord than in PVN.3. Intraperitoneal OT has no effect on mechanical hypersensitivity in incisional rats, but intrathecal and intracerebralventricular administration can dose dependently depress the hypersensitivity.4. The analgesia effect of OT can be totally inhibited by i.t.h or i.c.v atosiban, but partly depressed by administration of naloxone intrathecally or intracerebralventricularly.