Neurohormonal effects of oxytocin and vasopressin receptor agonists on spinal pain processing in male rats

Oxytocin (OT) and arginine vasopressin (AVP) are 2 neuropeptides that display well-known effects on the reproductive system. Although still controversial, oxytocin and vasopressin were demonstrated to exert potent effects on the nociceptive system when administered directly in various central nervous structures. On the other hand, little is known about their peripheral (hormonal) actions on nociception and pain responses. The aim of the present work was to characterize the effects of physiological blood concentrations of OT and AVP on spinal nociception and on pain responses. To do so, growing doses of OT or AVP were administered intravenously and the nociceptive processing by spinal cord neurons was analyzed in anesthetized male rats in vivo. We observed that the action potentials mediated by C-type nociceptive fibers was strongly reduced (antinociception) after intravenous injections of low doses of OT (<5 μg) or AVP (<500 pg), whereas an increase (pronociception) was observed at higher doses. Interestingly, antinociceptive and pronociceptive effects were fully abolished in the presence of the OT receptor antagonist and the AVP receptor antagonist type 1A (V_1A), respectively. We confirmed this result with a behavioral model of forced swim stress-induced analgesia associated with plasmatic release of OT (and not vasopressin). Stress-induced analgesia was transiently lost after i.v. administration of OTR antagonist. Together, the present work provides straightforward evidence that blood levels of OT and AVP modulate nociception, windup plasticity and pain responses. The final target structures explaining these effects remains to be identified but are likely to be C-type nociceptors.     

针刺足三里穴对大鼠下丘脑催产素、加压素mRNA表达的影响

目的研究针刺足三里穴对下丘脑催产素、加压素mRNA的表达在不同时间点的特异性影响。方法将 78只SD雄性大鼠分为针刺足三里穴位组、针刺足三里穴位旁开点组、束缚组、正常对照组 ,应用RT PCR方法观察针刺后 2、4、6、8h的下丘脑催产素、加压素的表达情况 ,经图像分析系统照相并进行半定量分析。结果针刺穴位旁开点后 2、4h下丘脑催产素的表达与其他 3组相比具有显著差异 (P <0 0 5 ) ,针刺后 6、8h各组间相比无显著性差异 (P >0 0 5 )。针刺后 2、4、6、8h ,针刺足三里穴位组的加压素表达较其他 3组均降低 ,有显著性差异 (P <0 0 5 )。结论针刺穴位旁开点可以引起催产素短时间的表达增高 ,而穴位点刺激并不引起催产素的表达变化。针刺足三里穴位可以引起加压素长时间表达受抑制 ,针刺穴位旁开点对下丘脑加压素的表达无影响。     

Structure activity relationship studies with C-terminal fragments of vasopressin and oxytocin on avoidance behaviors of rats

The potency of various C-terminal fragments of the neurohypophyseal hormone [Arg8]vasopressin [AVP-(1-9)] was determined using different avoidance behavioral test procedures in rats. Passive avoidance behavior was facilitated by these peptides. The fragments [Cyt6]AVP-(5-8) and [Cyt6]AVP-(5-9) were the most potent peptides tested after postlearning injection (consolidation) and preretention treatment (retrieval), respectively, after s.c. treatment. Comparable results were found when the peptides were injected into the lateral brain ventricle, but after this route of administration the peptides were about 3 to 4 order of magnitude more potent as compared to the s.c. route. Pentylenetetrazol-induced retrograde amnesia was reversed by AVP-(1-9) and various C-terminal fragments. In this respect [Cyt6] AVP-(5-9) and [pGlu4,Cyt6]-AVP-(4-9) appeared to be the most potent peptides. Injection of AVP-(1-9) and various C-terminal fragments after the acquisition of pole-jumping avoidance behavior induced resistance to extinction of the behavior. The fragment [pGlu4,Cyt6]AVP-(4-8) was the most potent peptide for this effect. Passive avoidance behavior was attenuated by s.c. administered oxytocin [OXT-(1-9)] and various C-terminal fragments. [pGlu4,Cyt6]-OXT-(4-9), [pGlu4,Cyt6]OXT-(4-8) and [Cyt6]OXT-(5-8) were the most potent of the peptides tested after postlearning administration, whereas [Cyt6]OXT-(5-9) was the most potent sequence after preretention injection. In all experiments the effects of the peptides were dose-dependent and of a long term nature. The results show that C-terminal fragments of the neurohypophyseal hormones potently modulate various aspects of memory processes, as assessed with different avoidance behaviors.(ABSTRACT TRUNCATED AT 250 WORDS)