Effect Of Acupoint Heat Stimulation On Neuropathic Pain In Phantom Limb Pain Model Rats And Its Mechanisms

Phantom limb pain(PLP)is defined as painful sensations referred to the amputated limbs.As a subtype of chronic neuropathic pain,PLP makes great trouble to the amputees.Our previous researches revealed that non-painful,43℃ heat stimulation could activate the endogenous descending inhibitory modulation on pain without irritating the descending facilitatory system.And it provides a new strategy for the treatment of chronic pain.In addition,evidences showed that the thalamic ventromedial(VM)nucleus was involved in the descending inhibitory modulation on pain.In the present study,the potential influence of acupoint innocuous heat stimulation at ST36(Zusanli)on endogenous descending modulation of pain were investigated by observing variations of noxious hind paw withdrawal reflex in PLP model rats.Moreover,involvement of the thalamic VM nucleus associated with pharmacological mechanisms underlying the descending regulation of nociception were systematically explored.The present experimental data may provide new evidence and thinking in clinical effectively treatment of PLP.Objective:1.To explore the potential effects of transection of different type of nerve,as sensory-,motor-and mixed nerve on PLP.2.To explore the effects of acupoint heat stimulation on neuropathic pain following different types of nerve transection.3.To explore the roles of thalamic VM nucleus in the treatment of phantom limb pain by acupoint heat stimulation at 43℃.Methods:1.Establishment of phantom limb pain model: different types of nerves of the sciatic nerve branches in rats were transected to simulate phantom limb pain.The common peroneal nerve(mixed nerve),tibial nerve(motor nerve)and sural nerve(sensory nerve)was transected respectively.2.Acupoint heat stimulation: 8 days after nerve transection,single heating-needle was inserted intramuscularly into the Zusanli acupoint on the contralateral side to nerve injury side,the temperature of heating-needle stimulation was at 43°C,and lasted for 30 minutes,the depth of insertion of heating-needle was 0.5 cm.Acupoint single needle stimulation without heating for 30 minutes was set as control.3.Intracerebral microinjection: one day after acupoint heating-needle stimulation,different doses of TRPV1 receptor antagonists were administrated into thalamic VM nucleus.Observation indicators:The paw withdrawal reflex elicited by noxious mechanical and heat stimulation was observed 8-14 days post the nerve transection.And differences in neuropathic pain induced by transection of different types of nerve were analyzed.The paw withdrawal reflex elicited by noxious mechanical and heat stimulation was observed 1-7 days post the acupoint heating-needle stimulation.The effects of acupoint heating-needle stimulation on neuropathic pain were evaluated.In addition,the paw withdrawal reflex elicited by noxious mechanical and heat stimulation was observed 0.5-4h after administration of TRPV1 receptor antagonist into thalamic VM nucleus.Results:1.Neuropathic pain induced by transaction of different types of nerveCompared with na?ve rats and rats with sham nerve lesion,significant mechanical hyperalgesia and heat hypoalgesia were observed following transection of mixed nerve and motor nerve(P < 0.05),which lasted for 7 days.No significant changes in sensory nerve transection group were observed(P > 0.05).2.Heat stimulation at 43℃ for 30 minutes at Zusanli acupoint could significantly enhance heat hypoalgesia,and the effect lasted for 3-4 days(P < 0.05);no significant changes in paw mechanical withdrawal reflexes were observed(P > 0.05).3.Microinjection of TRPV1 receptor antagonist AMG9810 into thalamic VM nucleus could depress heat hypoalgesia induced by heat stimulation at 43℃ in a dose-dependent manner(P < 0.05).Conclusion:1.More significant neuropathic pain was induced by transection of motor nerve and mixed nerve than that of sensory nerve.2.43 ℃ heat stimulation at Zusanli acupoint for 30 minutes could activate endogenous descending inhibition of pain,and enhance heat hypoalgesia in phantom limb pain model rats.3.TRPV1 receptor in thalamic VM nucleus play roles in the endogenous descending inhibition of pain induced by 43℃ heat stimulation at Zusanli acupoint.