内侧丘脑不参与电针对疼痛记忆模型大鼠诱发情绪的干预作用

INTERVENTION EFFECT ON ELECTROACUPUNCTURE ON PAIN-INDUCED AFFECTION IN A PAIN MEMORY RAT MODEL AND THE MECHANISM OF CORRELATION WITH THE MEDIAL THALAMUS

目的:通过损毁内侧丘脑(Medial thalamus, MT),明确MT在疼痛记忆模型大鼠疼痛感觉及诱发情绪中的作用及电针干预作用。方法:将51只健康雄性SD大鼠随机分为5组:空白组(C)、模型组(M)、模型+电针组(M+EA)、损毁+模型组(L+M)、损毁+模型+电针组(L+M+EA),除C组外其余各组大鼠双侧后足足底交叉注射角叉菜胶(Carrageenan, Carr),两次注射时间间隔14 d以建立疼痛记忆模型,其中L+M、L+M+EA组大鼠于实验开始前7 d行双侧MT损毁术,M+EA组、L+M+EA组大鼠分别于Carr首次左后足注射后5 h、1～5 d予电针治疗。分别在Carr首次注射前1 d、首次注射后4 h、1 d、5 d、13 d、15 d检测后足机械缩足阈(paw withdrawal threshold, PWT);分别在Carr首次注射前1 d、首次注射后1 d、5 d、13 d、15 d,检测厌恶性情绪;于Carr首次注射后16 d检测焦虑样情绪;采用尼氏染色确定MT损毁位置。结果:Carr首次注射后4 h、1 d,与C组比较,其余四组大鼠PWT与Carr首次注射前PWT的差值(paw withdrawal threshold difference value, PWT D-value)均显著降低(P<0.01)。Carr二次右后足注射后,与C组比较,M组、EA组、L+M组大鼠右后足PWT D-value值均显著降低(P<0.01, P<0.01, P<0.05),与M组比较,L+M、L+M+EA组大鼠PWT D-value显著增加(P<0.01)。Carr二次右后足注射后1 d,与M组比较,M+EA组、L+M+EA组大鼠CPA score值显著升高(P <0.01)。与M组、L+M组大鼠比较,M+EA组大鼠中央区域运动时间、中央区域运动距离均增多(P> 0.05),L+M+EA组中央区域运动时间显著增多(P<0.05);与C组同期比较,M组大鼠总运动距离显著下降(P<0.01),L+M组、L+M+EA组大鼠总运动距离均显著增加(P<0.01);与M组比较,M+EA组、L+M组、L+M+EA组大鼠总运动距离均显著增多(P <0.05, P <0.01, P <0.01);与M+EA组同期比较,L+M组、L+M+EA组大鼠总运动距离均明显增加(P<0.01)。结论:MT损毁后明显影响疼痛记忆模型大鼠的疼痛感觉但不对疼痛诱发情绪产生影响,早期电针干预具有抑制MT损毁后疼痛记忆模型大鼠疼痛感觉与疼痛诱发情绪产生的作用,其干预机制可能不是通过MT这一核团实现。

Objective: By lesioning the Medial thalamus (MT), to investigate the role of the MT in pain perception and pain-induced affection of pain memory rat model and the intervention effect of electroacupuncture. Methods:Fifty-one healthy, male, Sprague Dawley rats were randomly divided into control (C), model (M), model + electroacupuncture (M + EA), lesion+model (L + M), and lesion+model+EA (L + M + EA) groups. The pain was created by cross-injection of Carrageenan (Carr) on both hindpaws, respectively. Rats in the L + M and L + M + EA groups were withstand to bilateral MT lesions at 7 d before start of the experiment. Rats in groups of M + EA and L + M + EA were given electroacupuncture intervention at the time of 5 h, 1-5 d after Carr first injection. Detection of changes of Paw withdrawal threshold (PWT) of rats at different time point (including 1 d before Carr first injection, 4 h, 1 d, 5 d, 13 d, 15 d after Carr first injection). Detection of changes of rats' aversive affection at five different time point (including 1d before Carr first injection, 1 d, 5 d, 13 d, 15 d after Carr first injection ). Detection of anxiety or depression like affection at day 15 after Carr first injection;Nissl' s staining was used for determining the location of the MT lesions. Results: Compared with C group, paw withdrawal threshold (PWT D-value) of other 4 groups after Carr first injection has a statistically significant difference at 4h, 1d compared with baseline (P < 0.01). Compared with C group, there was a statistically significant difference PWT D-value in M, EA, and L + EA group (P < 0.01, P < 0.01, P < 0.05) after Carr second injection at right hindpaw. Compared with M group, PWT D-value of L + M and L + M + EA rats increased obviously. Compared with C group, the CPA score of M group and L + M group was decreased significantly after Carr second injection at right hindpaw (P < 0.01). Compared with M group, the CPA score of M + EA group and L + M + EA group was increased obviously one day after Carr second injection at right hindpaw (P < 0.01). Compared with M group and L + M group, the travelled distance and the time spent in centre zone increased in M + EA group (P > 0.05), the time spent in centre zone of L + M + EA group was increased obviously (P < 0.05). Compared with C group, the total travelled distance of M group was decreased significantly (P < 0.01), but increased obviously in L + M and L + M + EA group (P < 0.01). Compared with M group, the total travelled distance of M + EA group, L + M group and L + M + EA group increased significantly (P < 0.05, P < 0.01, P < 0.01). Compared with M + EA group, the total travelled distance of L + M, L + M + EA group increased obviously (P < 0.01). Conclusion: Lesioning the MT significantly relieves pain perception of pain memory but does not change pain-induced affection , early electroacupuncture pretreatment can restrain pain perception and pain-induced affection of pain memory, but its intervention mechanism may not be achieved through the MT.