Effect Of Morphine On The P2X₃ Receptor Expression In The Dorsal Root Ganglion In Rats Of Neuropathic Pain

Background: Neuropathic pain is the result from centralsensitizationand peripheral sensitization. Recently study found that the most importantmethod that prevent centralsensitization is inhibiting peripheralsensitization. P2X₃ receptor played a key role in development ofperipheral sensitization. Therefore, it had very important meaning toinvestigate the inhibition of P2X₃ receptor in peripheral sensitization d forpain mechanism.Objective: To observe the effects of intraperitoneal (i.p.) differentdoses of Morphine on thermal hyperalgesia and the expression of P2X₃receptor of dorsal root ganglion in rats treated with chronic constrictioninjury (CCI) to the sciatic nerve by applying immunohistochemistrymethods.Methods: 30 SD male rats weighting 180—220g, were randomlydivided into 5 subgroups(n=6). Sham—operated group (S group):expose sciatic nerve no ligation; normal saline group (NS group): CCImodel was successfully established, i.p. normal saline 2.0ml from 4 daysto 14 days after operation; morphine 2.0mg/kg group(M1 group) andmorphine 5.0mg/kg group(M2 group): morphine 2.0mg/kg, 5.0mg/kg wasintraperitoneal administered from 4 days to 14 days after operation;morphine 5.0mg/kg+naloxone 1.0mg/kg (M+N group): i.p. naloxone 1.0mg/kg 10 min later, i.p. morphine 5.0mg/kg. All drugs were diluted inphysiological saline to 2.0ml.CCI model was produced according to themethod described by Bennett. Rats were tested for hyperalgesia bymeasuring thermal withdrawal latency (TWL) using heat radiostimulation.The animals were decapitated 14 days after operation, The right L4 dorsalroot ganglia was quickly removed and The P2X₃ recepter expression inthe surgical side L4 dorsal root ganglions in each group was assayedusing immunohistochemistry methods.Results: (1) Set up CCI model successfully. The TWL of Rats inNS group was significant lower than S group and baseline value of itsown. (2) The P2X₃ recepter expression in the surgical side L4 dorsal rootganglion of NS group was significant increased than S group 14 daysafter operation. (3) Compare to NS group, high dose of morphine (M2group) significantly reliefed thermal hyperalgesia as well as significantlyinhibited the P2X₃ recepter in the surgical side L4 dorsal root ganglion14 days after operation; analgesia effect of low dose of morphine (M1group) and its effect on the P2X₃ recepter expression Compare to NSgroup, there was not significant difference.Conclusions: (1) Dorsal root ganglion P2X₃ receptors expressionobviously increased in chronic constriction injury (CCI) to the sciaticnerve rat models, which suggests that P2X₃ receptors might play animportant role in neuropathic pain. (2)intraperitoneal morphine 5.0mg/kg provid a significant analgesic effect on neuropathic pain rats, as well assignificantly inhibit the increase of dorsal root ganglion P2X₃ receptors,which indicates that the inhibition of the expression of dorsal rootganglion P2X₃ receptors is one of the periphery mechanisms forintraperitoneal morphine analgesia.