Exacerbated mechanical hyperalgesia in rats with genetically predisposed depressive behavior: role of melatonin and NMDA receptors.
Exacerbated mechanical hyperalgesia in rats with genetically predisposed depressive behavior: role of melatonin and NMDA receptors.
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具有遗传倾向抑郁行为的大鼠机械性痛觉过敏加剧：褪黑激素和 NMDA 受体的作用
DOI：
10.1016/j.pain.2012.08.016
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发表时间：
2012-12
期刊：
影响因子：
7.4
通讯作者：
Mao J
中科院分区：
文献类型：
--
作者：
Wang S;Tian Y;Song L;Lim G;Tan Y;You Z;Chen L;Mao J
疼痛和抑郁症之间的联系在临床上早已被认识到;然而，其机制仍不清楚。在这项研究中，我们表明，机械性痛觉过敏引起的单侧颞下颌关节（TMJ）炎症加重了Wistar-Kyoto（WKY）大鼠与遗传倾向的抑郁行为。反过来，颞下颌关节炎症增强抑郁行为，这样一个较低的伤害性阈值与抑郁行为在相同的WKY大鼠较高的分数。与Wistar大鼠相比，WKY大鼠血浆褪黑素水平降低，同侧三叉神经尾侧亚核（Sp 5C）褪黑素MT 1受体表达下调，NMDA受体NR 1亚基表达上调。脑池内注射6-氯褪黑素（250μg，每日2次× 7天）可同时减轻WKY大鼠的机械性痛觉过敏和抑郁行为，并下调同侧Sp 5C中NR 1的表达。在膜片钳记录中，褪黑素剂量依赖性地降低脊髓背角胶状质神经元NMDA诱导的电流。这些结果表明，颞下颌关节炎症引起的机械性痛觉过敏和抑郁行为之间的相互关系，并建议，中央褪黑激素能系统，通过调节NMDA受体的表达和活性，可能在疼痛和抑郁症之间的并发症的机制中发挥作用。
A connection between pain and depression has long been recognized in the clinical setting; however, its mechanism remains unclear. In this study, we showed that mechanical hyperalgesia induced by unilateral temporomandibular joint (TMJ) inflammation was exacerbated in Wistar-Kyoto (WKY) rats with genetically predisposed depressive behavior. Reciprocally, TMJ inflammation enhanced depressive behavior such that a lower nociceptive threshold correlated with a higher score of depressive behavior in the same WKY rats. As compared with Wistar rats, WKY rats exhibited a lower plasma melatonin level, downregulation of the melatonin MT1 receptor, but upregulation of the NR1 subunit of the NMDA receptor in the ipsilateral trigeminal subnucleus caudalis (Sp5C). Intracisternal administration of 6-chloromelatonin (250μg, twice daily × 7 days) concurrently attenuated mechanical hyperalgesia and depressive behavior in WKY rats as well as downregulated the NR1 expression in the ipsilateral Sp5C. In patch-clamp recordings, melatonin dose-dependently decreased NMDA-induced currents in spinal cord dorsal horn substantia gelatinosa neurons. These results demonstrate a reciprocal relationship between TMJ inflammation-induced mechanical hyperalgesia and depressive behavior and suggest that the central melatoninergic system, through modulation of the NMDA receptor expression and activity, may play a role in the mechanisms of the comorbidity between pain and depression.
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DOI：
10.4088/jcp.08m04367
发表时间：
2009-09
期刊：
The Journal of clinical psychiatry
影响因子：
--
作者：
Barry DT;Beitel M;Garnet B;Joshi D;Rosenblum A;Schottenfeld RS
通讯作者：
Schottenfeld RS
影响因子：
5.5
作者：
Grudt, TJ;Perl, ER
通讯作者：
Perl, ER
影响因子：
6.6
作者：
Bonnewyn, A.;Katona, C.;Demyttenaere, K.
通讯作者：
Demyttenaere, K.
影响因子：
120.7
作者：
Dobscha, Steven K.;Corson, Kathryn;Gerrity, Martha S.
通讯作者：
Gerrity, Martha S.
影响因子：
9.8
作者：
D'Mello, R.;Dickenson, A. H.
通讯作者：
Dickenson, A. H.