| The pain and discomfort caused byorthodontic treatment have been considered as tough problems in orthodontic practice.Pain is almost inevitable and the most unpleasant reaction for the orthodontic patient. It begins a few hours after the application of an orthodontic force, lasts for3-5days approximately. Pain is a determinating variable of adherence to orthodontic treatment because the idea of having a painful experience discourages many patients from such treatment.Previous research demonstrated that orthodontic pain was caused by a process of edema, ischemia, inflammation in periodontal ligament, which may lead to the release of nociceptive mediators such as SP, CGRP resulting in neuronal activation. However, the current available analgesics could not relieve all the orthodontic pain, largely because the underlying mechanisms for orthodontic pain are far from being revealed. Previous experiments shown that tooth movement can stimulated the Fos protein expression in spinal trigeminal subnucleus caudalis (SpVc), one of the important relay nuclei for processing the nocicetptive information from the orofacial region.recently researches shown that glia, including astrocyte and microglia, play an important role in the initial induction and maintenance of chronic pain in the central neural system (CNS).Several inflammation animal model show oro-facial stimulus can Current pain theory has been shifted from a pure neuronal to contribution to neuronal-glia interaction.Can tooth movement stimulate neuronal-glia interaction involving neuron, microglia and astrocytein SpVc? If so, it will provide an new explanation for the orthodontic pain.Chronic pain and anxiety are prevalent and frequently co-occur,several studies have assessed the impact of pain on anxiety outcomes, there is substantial literatures on the effects of anxiety and learning and memoryfrom behavioral and pharmacologic perspectives. Our purpose was to examine the association between experimental tooth movement (ETM) and anxiety.if so, can anxiety evoked by ETM functional impair the spacial learning and memory inhippocampusof rat?Danggui-Shaoyao-San (DSS) is a traditional herbal medicine. It is first recorded in "JinKuiYaoLue".Recentexperiment evidence showed that DSS possesses antioxidative, cognitive enhancing and antidepressant effects. Further study suggested that the effect of DSS is related with the reversion of brain noradrenaline concentrations under depressive conditions. However, the potential analgesic effect of DSS and its underlying mechanism have not been investigated. One shared effect for first line antidepressant is analgesia for different pain modalities, eg duloxetine is efficacious for both severe depression and pain. Thus we hypothesized that DSS also possesses analgesic effect for orthodontic pain. Since glia system is involved in both depressionand pain, the potential analgesic mechanismsforantidepressant is inhibiting the interaction between neuron and glia. Thus we raised the hypothesis that DSS also possesses analgesic effect for orthodontic pain, and the possible analgesic mechanism for DSS is inhibiting the interaction between neuron and glia in SpVc.1. Effects of Danggui-Shaoyao-san on the expression of Fos, iba1and GFAPin SpVc after ETM in ratObjective:To observe spatial and temporal distribution of Fos protein and actived glia, including microglia and astrocytein SpVc duing ETM and its underlying neuron-glia interaction mechanisms for DSS’s analgesia on orthodontic pain.Methods:Rats were randomly divided into naive,sham,ETM, DSS plus ETM (DETM) groups, rats were pregavaged with DSS in the DETM groups. The right upper-first-molar was moved mesially described by Colin K.for rats in ETM and DETM groups, vacuous chewing movements (VCM) were evaluated at4h,12h,1,3,5and7d after operation. Immunofluorescent histochemistry analysis were used to quantify the Iba-1,GFAP and Fos expression levels in SpVc.Based on the behavioral feature and Fos or Iba-1expression data, the Iba-1and Fos expression of west-blot were only investigated at1d after operation in DETM group. Results:1.The duration of VCM per unit-time was found significantly increased at4h in ETM group, peaked1d, and then decreased continuously until7d as compared with the sham group. The duration of VCM per unit-time in DETM group was expectedly lower than ETM group. However, a drastic peak increase of Vc Fos expression was observed at4h and gradually decreased after7d; while the increased Iba-1level reached the peak at1d after operation and gradually decreased after7days and GFAP reached the peak at7d after operation and gradually decreased. Furthermore, treatment with DSS significantly attenuated the ETM induced spontaneous pain. In parallel with the behavioral observations, pretreatment with DSS (for5days) significantly attenuated the Fos and Iba-1levels at1d after ETM operation.Conclusions:1.change of VCM can be a reliable measure for tooth-movement pain in rats, which could be widely used in investigating the orthodontic pain mechanism.2.0ur data suggested that treatment with DSS has significant analgesic effects for ETM induced pain, which is accompanied with inhibition on both neuronal and microglial activation. The present study offered evidence that the traditional Chinese medicine DSS has analgesic effects via inhibiting microglia and neuronal activation at the primary integration site of orofacial nociceptive information, SpVc.2. Effects of Danggui-Shaoyao-san on the influence of spacial learning and memory evocked by experimental tooth movementObjective:To investigate methods the relationship betweenpainand anxietyduring ETM in ratscombined methods including behavioral testing, molecular neurobiology and morphology, we investigated the underlying mechanisms of astrocytes invloved in the impairment of learning and memory evoked by ETM, and the effects of DSS on synaptic plasticity in hippocampus and its possible therapeutic mechanisms.Methods:The level of anxiety behavior were measured by the open field test and elevated plus maze test;Morris water maze testwas performed to test the change of learn and memory in the ETM rats with or without DSS administration; Iimmunofluorescent histochemistry was used to detect the expressions of astrocytic GFAP in hippocampus; immunofiuorescent Western blot was performed to observe the change of astrocytic GFAP in hippocampus; Dil staining method was performed to test the density of spines with3D analyzing method and detailed changes in hippocampus in the ETM rats with or without DSS administration.Results:Parameters related to anxiety were higher in the ETM group compared to the shanm group,Statistically significant differences in anxiety-related behavior between sham and ETM group were found4h after ETM and pain-related behavior was significantly greater in the ETM group than in the shaml group at1d;Parameters related to learning and memory were lower in the ETM group compared to the shamgroup7d after ETM, the DSS significantly increased parameters related to learning and memory in EDTM rats compared to the ETM group; Astrocytic GFAP is significantly upregulated1d after ETM in the hippocampus, the DSS was significantly decreased express of GFAP in EDTM rats compared to the ETM group; The spine density, mean spines area and volume were decreased in ETM group, but the DSS administration could increase the spine density compared to the ETM group.Conclusions:The ETMcould increase anxietyin rat that maybeprecede the appearance of periodontal pain in rat;DSS could block ETM-induced decrease of learning and memory behavior. Thedecreased spines density in hippocampus in the ETM rats may be related with the decline of the ability of learn and memory. The ability to change the synaptic plasticity after DSS administration may be correlated with the alleviation of impairment of learn and memory after ETM. |
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