Plasticity Of Endogenous Regulation Of Pain And Regulation Of Thermal Stimulation In Acute Visceral Pain

Visceral pain is pathological pain and common clinical disease caused by noxious stimulation of internal organs.Previous studies found that the endogenous regulation of pain under pathological pain state has plastic changes,which is manifested in the homeostatic imbalance between the endogenous descending inhibition and facilitation.However,whether visceral pain is also accompanied by a homeostatic imbalance in the endogenous modulation of pain has not been revealed.Although the research group had previously proposed warm stimulation by means of non-painful heat stimulation,it is not clear whether these treatments can effectively control of visceral pathological pain.In the current study,the bilateral nociceptive paw withdrawal reflexes elicited by mechanical and thermal stimulation in rats were evaluated to explore the possible changes of endogenous descending control of pain.The effects of heating-needle stimulation at different temperatures,i.e.43-46? on the endogenous descending regulation of pain in rats suffered from visceral pain and its mechanism were studied.Purposes: 1.To explore the changes of endogenous descending modulation of pain in rats with visceral pain.2.To investigate the effect of intramuscular(i.m.)heating-needle stimulation at different temperatures on the endogenous descending control of pain in rats with visceral pain.3.To explore the central mechanism mediated by thalamic VM nucleus and MD nucleus in the treatment of visceral pain by i.m.heat stimulation at different temperatures.Methods: 1.Acute visceral pain model was induced by intraperitoneal injection of 1% acetic acid in rats.The paw withdrawal mechanical threshold and the paw withdrawal thermal latency of bilateral hind limbs were observed before modeling,3 hours and 1-7 days after modeling.2.Rats were intraperitoneally injected with 1% acetic acid.One day after the injection,a period of 30 minutes warm stimulation at temperature of either 43? or 46? were given into unilateral gastrocnemius muscle.The paw withdrawal mechanical threshold and the paw withdrawal thermal latency of bilateral hind limbs were observed at 1h,3h,and 1-6d after the heating needle stimulation.3.Seven days after the recovery of rat brain internal tube,rats were intraperitoneally injected with 1% acetic acid.One day after the establish of visceral pain model,rats were given unilateral gastrocnemius muscle warm stimulation at temperature of 43? and 46? for 30 minutes.One day after the treatment,the thalamic VM and MD nuclei were microinjected with different doses of P2X3 receptor antagonist A-317491,respectively.After than,the bilateral paw withdrawal mechanical threshold and the paw withdrawal thermal latency were observed at 0.5h and 1-4h after the microinjection of P2X3 receptor antagonist A-317491.Experimental results: 1.One day after the establish of visceral pain model,the rat's bilateral hind limbs appeared obvious mechanical hyperalgesia.1-5 days after modeling,the paw withdrawal mechanical threshold of bilateral hind limbs in the model group decreased significantly,and the difference was statistically significant compared with the normal saline group(P<0.05).After modeling,there was no obvious change in the paw withdrawal thermal latency of the rats in the model group.2.One day after modeling,the unilateral hind limb gastrocnemius muscle was stimulated with unheated acupuncture and 43? and 46? for 30 min,and the mechanical withdrawal reflex threshold of rats in the unheated acupuncture group and the 43? treatment group did not change significantly.The mechanical withdrawal reflex threshold of bilateral hind limbs of rats in the 46? treatment group was significantly decreased,and the difference was statistically significant compared with the non-heated acupuncture group and the 43? treatment group(P<0.05).The paw withdrawal thermal latency of both hind limbs in the 43? and 46? treatment groups was significantly longer than that in the non-heating needle group,and the difference was statistically significant(P<0.05).Compared with the 43? treatment group,the 46? treatment group had a higher paw withdrawal thermal latency in the bilateral hind limbs,and the difference was statistically significant(P<0.05).3.Microinjection of different doses of P2X3 receptor antagonist A-317491 into VM nuclei in the brain can dose-dependently reverse the thermal pain response in rats with visceral pain induced by thermal stimulation in the gastrocnemius muscle at 43? and 46? for 30 min.Intracerebral MD nuclei microinjection of different doses of P2X3 receptor antagonist A-317491 dose-dependently inhibited the increase of mechanical pain response in rats with visceral pain induced by intramuscular stimulation at 46? for 30 min.Conclusions: 1.One day after the establish of visceral pain in rats,developed mechanical hyperalgesia was found in bilateral hind limbs,which lasted over 5 days.2.A period of 30 min of intramuscular stimulation with warm needle at temperature of 43? activated the descending inhibitory effect in rats with visceral pain,while intramuscular stimulation with heat stimulation at 46? for 30 min simultaneously activated both descending facilitation and inhibition in rats suffered from visceral pain.3.P2X3 receptors in the VM nucleus of the thalamus were involved in the enhancement of descending inhibition induced by heat stimulation at 43? and 46? in rats with visceral pain.P2X3 receptors in the thalamic MD nucleus involved in the descending facilitation induced by intramuscular heating needle stimulation at 46? for 30 min.