Nicotine Abstinence Induced Pain Sensitization And Changed The Resting State Of The Brain Nucleus

1 Background and ObjectiveThe Investigation Report on Chinese Adult Tobacco of 2015 showed that the total number of adult smokers in China was 316 million,and 15.2 cigarettes were consumed by the average of smokers per day.Smoking rate for male was 52.1%,and more than 740 million were secondhand smokers.Smoking patients were often asked to quit smoking for 1-2 weeks before operation in order to reduce postoperative complications of respiratory system in clinical practice.In this paper,the postoperative pain of abstinent smoking patients was exploered,and the brain function mechanism of them was mainly talked about,so that could conclude the appropriate treatment protocols.Some clinical retrospective studies and prospective cohort studies found that the abstinent smoking patients suffered more severe postoperative pain and analgesic consumption,even the more opioids played an common efffects.Our previous animal research found that the pain threshold and the 5 hydroxytryptamine(5-HT)in the cerebrospinal were decreased in the nicotine addiction withdrawal rats,and the tryptophan hydroxylase 2(TPH 2)in the rostral ventromedial medulla(RVM)in which the 5-HT was mainly synthesis also was decreased.However,this phenomenon could be reversed by injecting the 5-HT into the intracerebral.5-HT has analgesic effect,and tramadol was widely used as analgesic in clinical with partial agonisting opioid receptor and inhibition serotonin(5-HT)and noradrenaline reuptake,increasing the 5-HT and NA in the brain.So we purposed the tramadol could effectively reduced the postoperative analgesic requirements in the abstinent smoking patients by inhibition the 5-HT reuptake,increasing the concentration of 5-HT in synaptic space,and partially improving the reduction of 5-HT caused by nicotine withdrawal in nicotine dependent patients.2 MethodsWe first conducted a 2 by 2 factorial clinical design,in which smoking history(nicotine dependent and nicotine independent)and postoperative analgesics(sufentanil and tramadol)acted as two parallel factors.Whether tramadol could reduce the postoperative analgesic requierments in the abstinent smoking patients was explored by calculating the amount of postoperative analgesic use.Then we performed an observational cohort study to explore the change of brain function by calculating the regional homogeneity(ReHo),amplitude of low frequency fluctuation(ALFF),and fractional amplitude of low-frequency fluctuation(fALFF)using resting state functional magnetic resonance imaging(rs-fMRI)technology.Pain threshold was also measured using the Von Frey mechanical stimulation and electrical stimulation,and analysed their correlation with ReHo.At last,we presented a proposal of procedural postoperative analgesia for abstinent smoking patients based on our results and the inference of the change of brain function.3 Results3.1 The result of the 2 by 2 factorial clinical design3.1.1 The P value of the interaction of smoking history and postoperative analgesics is 0.0005 by using the variance analysis of factorial design to the additional analgesic requirements.This means that postoperative analgesic requierment is influenced by the history of smoking in the sufentanil group and the tramadol group.In another words,tramadol could reduce the postoperative analgesic requirements for abstinent smoking patients compared with sufentanil and nicotine independented patients.3.1.2 There is significant interaction between the postoperative analgesics and time in tests of within-subjects effects to the visual analogue score using the repeated measures AVOVA,and the P value is 0.037.That is to say,tramadol could reduce the score of VAS during the postoperation.3.1.3 There is no significant defference among groups in postoperative nausea,vomiting,fever and other adverse by analysis the recorded score3.2 The result of the change of brain function in the abstinent smoking patients3.2.1 The value of pain sensitivity questionnaire(PSQ)and the pain threshold of Von Frey mechanical stimulation and electric stimulation was lower in the abstinent smoking patients than in the nicotine independented patients.That means,compared with nicotine independented patients,the abstinent smoking patients had more pain sensitivity.3.2.2 The value of the mReHo and mfALFF were both decreased in the medial frontal gyrus,inferior frontal gyrus,superior frontal gyrus,middle frontal gyrus,anterior cingulate,parahippocampal,olfactory,insula,caudate and rectus in the abstinent smoking patients.As the value of the ALFF was decreased in the medial frontal gyrus,frontal superior orbital gyrus.The above region in the abstinent smoking patients was dysfunction and had lower spontaneous activity.3.2.3 The pain threshold of Von Frey mechanical stimulation but not electric stimulation was positively related with the ReHo of bilateral thalamus in the abstinence.So the lower Reho of thalamus,the lower mechanical pain threshold in the abstinent patients.4 ConclusionThe probably mechanism of the sensitization of pain in the abstinent patients is that the dysfunction of the frontal cortex affected the function of 5-HT system and descending analgesia pathway,made more postoperative pain and to increase the postoperative analgesics requirements in the abstinent smoking patients.Tramadol could reduce it with its partial agonisting opioid receptor and inhibition 5-HT and NA reuptake,without affecting postoperative nausea and vomiting,fever and other adverse.Therefore,tramadol was recommended for abstinent smoking patients,which could be effective in the treatment of postoperative pain.