A single subanesthetic dose of ketamine relieves depression-like behaviors induced by neuropathic pain in rats.
A single subanesthetic dose of ketamine relieves depression-like behaviors induced by neuropathic pain in rats.
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DOI：
10.1097/aln.0b013e31822f16ae
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发表时间：
2011-10
期刊：
影响因子：
8.8
通讯作者：
Ziff EB
中科院分区：
文献类型：
--
作者：
Wang J;Goffer Y;Xu D;Tukey DS;Shamir DB;Eberle SE;Zou AH;Blanck TJ;Ziff EB
慢性疼痛与抑郁症有关。在啮齿类动物中，疼痛通常通过感觉超敏反应来评估，这并不足以测量情感反应。低剂量氯胺酮已被用于治疗疼痛和抑郁症，但目前尚不清楚氯胺酮是否可以缓解与慢性疼痛相关的抑郁症，以及这种抗抑郁作用是否取决于其抗伤害性。我们研究了备用神经损伤（SNI）模型的神经病理性疼痛是否诱导抑郁行为的大鼠，使用蔗糖偏好试验和强迫游泳试验，并测试是否亚麻醉剂量的氯胺酮治疗SNI诱导的抑郁症。与对照组相比，SNI治疗组大鼠表现出降低的蔗糖偏好（0.719 ± 0.068（平均值± SEM）vs.0.946 ± 0.010）和增强的不动性（107.3 ± 14.6s vs.56.2 ± 12.5s）。此外，假手术大鼠在术后急性期表现出抑郁行为（术后第2天为0.790 ± 0.062）。单次亚麻醉剂量的氯胺酮（10 mg/kg）未改变SNI诱导的超敏反应;然而，其治疗了SNI相关的抑郁样行为（给药后1天，氯胺酮为0.896 ± 0.020，对照组为0.663 ± 0.080;给药后5天，氯胺酮为0.858 ± 0.017，对照组为0.683 ± 0.077）。慢性神经性疼痛会导致抑郁样行为。术后时期也容易出现抑郁症，可能是由于急性疼痛。蔗糖偏好试验和强迫游泳试验可用于补充动物研究中用于评估疼痛的感觉试验。小剂量氯胺酮可治疗慢性神经病理性疼痛引起的抑郁样行为。
Chronic pain is associated with depression. In rodents, pain is often assessed by sensory hypersensitivity, which does not sufficiently measure affective responses. Low-dose ketamine has been used to treat both pain and depression, but it is not clear whether ketamine can relieve depression associated with chronic pain and whether this antidepressant effect depends on its anti-nociceptive properties. We examined whether the spared nerve injury (SNI) model of neuropathic pain induces depressive behavior in rats, using sucrose preference test and forced swim test, and tested whether a subanesthetic dose of ketamine treats SNI-induced depression. SNI-treated rats, compared with control, showed decreased sucrose preference (0.719 ± 0.068 (mean ± SEM) vs. 0.946 ± 0.010) and enhanced immobility in the forced swim test (107.3 ± 14.6s vs. 56.2 ± 12.5s). Further, sham-operated rats demonstrated depressive behaviors in the acute postoperative period (0.790 ± 0.062 on postoperative day 2). A single subanesthetic dose of ketamine (10mg/kg) did not alter SNI-induced hypersensitivity; however, it treated SNI-associated depression-like behaviors (0.896 ± 0.020 for ketamine vs. 0.663 ± 0.080 for control 1 day after administration; 0.858 ± 0.017 for ketamine vs. 0.683 ± 0.077 for control 5 days after administration). Chronic neuropathic pain leads to depression-like behaviors. The postoperative period also confers vulnerability to depression, possibly due to acute pain. Sucrose preference test and forced swim test may be used to compliment sensory tests for assessment of pain in animal studies. Low-dose ketamine can treat depression-like behaviors induced by chronic neuropathic pain.