| Objective: Diabetic neuropathic pain is one of the most commonlong-time complications of diabetes. The morbidity of diabetic neuropathicpain with depression in diabetics increases gradually, seriouslyaffecting the quality of diabetics ’ life. Compared with common people, theprevalence of depression may be reached1.6to2.0times in diabetics. Themorbidity of depression is as high as13%in type2diabetes. The mechanismof diabetic neuropathic pain with depression is complex, and it is known thatthe expression of GABABreceptor play an important role in the formation ofdepression. The agonists and antagonists of GABABreceptors have proved topossess anti-depression effect, but the action mechanism remains unclear.Only a better understanding of the specific mechanisms involved in depression,can it provide a new treatment strategy for the clinical treatment of depression.GABABreceptors widely distribute in the nervous system, regulatingsynaptic transmission. GABABreceptors in central nervous system associatedwith many central nervous system diseases, such as depression, anxiety, drugaddiction, pain and epilepsy. As the specificity agonists GABABreceptors,baclofen showed its effective in analgesic and antidepressant. Theantidepressant effect of CGP55845(the inhibitor of GABABreceptors) alsohas been demonstrated. The reducing of BDNF, whichresulted from different causes, often induce depression. The up-regulation ofBDNF can cause antidepressant effect. This suggests that BDNF is closelyrelated to the formation of depression. But it is unclear that if the expression ofGABABreceptors participate in the formation of depression by mediating theexpression of BDNF.The rats were made the model of DNP with depression after injection STZ (60mg/kg) and the forced swimming test. The agonists and antagonistsof GABABreceptors were administrated after model establishment. Methodsof immunohistochemistry, RT-PCR and Western blot were applied to examinethe expression of BDNF in hippocampus to explore the possibleantidepressant and analgesia mechanism of GABABreceptors.Methods: Thirty male Sprague-Dawley rats were randomly selected forthis experiment, weighing180-200g, provided by the Experimental AnimalCenter of Hebei Medical University,were randomly divided into two groups:normal control group(C group) and Diabetic neuropathic pain (DNP) modelgroup(D group), which rats were intraperitoneal injection saline orstreptozocin (STZ) respectively. Two weeks after intraperitoneal injection,fasting blood glucose was measured. The eligibility criteria of diabetic ratswas fasting blood glucose>16.7mmol/L. The15min forced swimming testwas applied to form depression model. The rats were placed in high40cm,20cm diameter cylindrical transparent tank, the depth of25cm, watertemperature25±2℃, and then swimming15min. The water in the tankshould be changed before swimming per time to avoid mutual influence. Threeweeks after intraperitoneal injection, von Frey Hairs mechanical pawwithdrawal threshold was measured (PWT), PWT <4g were qualified ratmodel of neuropathic pain (D group). The immobility time of forcedswimming test was recorded in5minutes. Compared with group C group, thesignificantly prolong of IMFST indicates that DNP with depression modelsuccessfully prepared. Combine behavior and molecular biology change todetermine the DNP with depression in rats.100male SD rats were randomly divided into two groups: normal controlgroup(C group) and Diabetic neuropathic pain with depression model group(Dgroup). The model rats were randomly divided into4groups (n=20, eachgroup) according to the injection medicines: saline10μl+saline10μl wereinjected intrathecally in D1group, baclofen0.5μg+saline10μl in D2group,CGP5584510μg+saline10μl in D3group，CGP5584510μg+baclofen0.5μgin D4group; saline10μl+saline10μl were injected intrathecally in20normal rats (C group) which rats were intraperitonealy injected saline. There was ainterval of15minutes between twice intrathecal injection in five groups for4days. The paw withdrawal threshold (PWT) and immobility time of forcedswim test(IMFST) were measured two hours after intrathecally injection (T1)and two weeks after intrathecally injection(T2) respectively.The hippocampusof rats were removed after measurement of PWT and IMFST for detection ofBDNF expression.Result: Compared with group C, the PWT was significantly lower (P<0.05), the IMFST was significantly longer (P<0.05), the expression of BDNFwas decreased(P<0.05) in group D. Compared with D1, the IMFST wassignificantly shorter (P<0.05) in group D2and D3, the expression of BDNFwas increased (P<0.05) in group D2and D3, the PWT was significantlyhigher (P<0.05) in group D2but showed no significant change in group D3;the PWT, IMFST and expression of BDNF showed no significant change ingroup D4Compared with D1. The PWT, IMFST and expression of BDNFshowed no significant change between T1and T2in five groups.Conclusion: GABABreceptors could make up-regulation of BDNF inhippocampus of rats with DNP with depression, and inhibit depressionsymptoms. |
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