| Background and purposeTrigeminal neuralgia(TN)is a neuropathic pain involving one or more branches of trigeminal nerve,characterized by sudden,severe,brief,and recurrent sense of pain.As frequent attacks and the severe pain,causing serious impact on the quality of patient's life.Although taking antiepileptic drugs can alleviate the symptoms,but with the development of the disease,patients need higher doses of the drug to achieve the same therapeutic effect,many patients can't tolerate the side effects,so they have to seek alternative treatments.at present,although lack rigorous clinical trials to confirm that it can treat TN effectively,the existing clinical research results show that the botulinum toxin type A(BoNT-A)might provide TN patients with significantly benefit,and does not cause obvious systematic adverse effect.But its mechanism is still unclear.thermoTRPs are a subfamily of transient receptor potential(TRP)channels,they can be activated by the change of environmental temperature,as the integrator of some signal transduction pathways.In the state of some pathological pain,Dysfunction of these channels can cause hyperthermalgesia and hyperalgesia.Researches have shown that BoNT-A might exert its antinociceptive in TN through inhibiting these channels ' expression in the endings of trigeminal nerve.TRPM3 and TRPV4 also belong to the same channel type,studies have shown that TRPM3 channel may play a role in hyperalgesia caused by injury of nerve or inflammation,TRPV4 channel associated with diabetic neuropathy and neuralgia caused by chemotherapy,and play a crucial role in mechanical hyperalgesia generated by inflammatory mediators.As for whether these two channels mediate the occurrence of TN and whether BoNT-A also exerts its antinociceptive effect through inhibiting the expression of the two channels in the endings of trigeminal nerve are still not clear.This will the focus topic of this study.MethodsUsing ION-CCI(Chronic Constriction Injury of the Infraorbital Nerve)to build the animal model of TN,the experimental rats were divided into four groups,control group,ION-CCI group,3U group,10 U group.Before building the model,using Von Frey filament to test the pain behavior of each group and record the data,after building the model,test the pain behavior of each group every other day and record the data,the 14 th day after surgery,treating each group respectively with the processing method described below: subcutaneous injection of 30 ul saline solution at the whisker pad in the former two groups,subcutaneous injection of 30 ul BoNT-A solution at the whisker pad in the latter two groups,according to 3U/Kg and 10U/ Kg to prepare the BoNT-A solution respectively,continue to test pain behavior in each group every other day and record the data,until 14 days after injection,get the target tissue,then dealing with the whisker pad ipsilateral to the injection using HE staining,using Western blot and Immunohistochemical technique test the expression level of TRPM3 and TRPV4in subnucleus caudalis of spinal trigeminal nucleus of each group.Results1.pain behavior test results: the experimental group appear obvious refractory period 2 days after operation,then the pain threshold is falling,pain threshold reach the bottom 14 days after operation,after the injection of BoNT-A,the pain threshold in 3U and 10 U group is rising,at 4 days after the injection of NoNT-A,the difference between either 3U or 10 U group and CCI group was statistically significance(p < 0.05),and this difference lasts until 28 days after operation.In addition,the difference of pain threshold between 3U and 10 U group has no statistically significance(p>0.05).2.HE staining of the whisker pad: no inflammatory response was observed in the subcutaneous tissue of the experimental groups and the control group.3.The expression of TRPM3 and TRPV4 results: compared with control group,the expression of TRPM3 and TRPV4 in ION-CCI group are increased and the differences are statistically significance(p<0.05).Compared with CCI group,the expression level of TRPM3 and TRPV4 in 3U and 10 U group are decreased and the differences is statistically significance(p<0.05),but between 3U and 10 U group,the expression level of TRPM3 and TRPV4 have no statistical difference(p>0.05).Conclusions1.The higher expression of TRPM3 and TRPV4 may mediate the formation of the mechanical hyperalgesia in rat model of TN.2.Subcutaneous injection of BoNT-A at whisky pad in rat model of TN can enhance the mechanical pain threshold and the antinociceptive effect.BoNT-A may exert its antinociception effect through inhibiting the above two channels' expression in the central terminal of trigeminal nerve. |
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