Neuroscience Research Institute and Department of Neurobiology, Peking University, Beijing, China.
J Pain. 2010 Mar;11(3):219-29. doi: 10.1016/j.jpain.2009.07.002. Epub 2010 Jan 21.
Although it has been accepted that depression and pain are common comorbidities, their interaction is not fully understood. The present study was aimed to investigate the effects of depression on both evoked pain behavior (thermal-induced nociception and hyperalgesia) and spontaneous pain behavior (formalin pain) in rats. An unpredictable chronic mild stress (UCMS) paradigm was employed to develop a classical depression. The emotional behaviors were assessed by sucrose preference test, open field test, and elevated plus-maze test. The results showed that the depressed rats always exhibited stronger tolerance to noxious thermal stimulation under both normal and complete Freund's adjuvant (CFA)-induced chronic pain conditions, when compared to nondepressed animals. Interestingly, the spontaneous nociceptive behaviors induced by formalin injection were significantly enhanced in rats exposed to UCMS in comparison to those without UCMS. Systemic administration of antidepressant fluoxetine significantly restored the nociceptive behaviors to normal level in depressed animals. An additional finding was that the inflammatory rats tended to display depressive-like behaviors without being exposed to UCMS. These results demonstrated that depression can have different effects on stimulus-evoked pain and spontaneous pain, with alleviation in the former while aggravation in the latter.
The present study provides evidence that depression can have divergent effects on stimulus-evoked and spontaneous pain by confirming that rats exposed to chronic mild stress tend to exhibit decreased pain sensitivity to experimental stimuli but increased intensity of ongoing pain. This may contribute to further understanding of the perplexing relationship between clinical depression and chronic pain.
尽管人们已经接受了抑郁和疼痛是常见的共病这一事实，但它们之间的相互作用仍未被完全理解。本研究旨在探讨抑郁对大鼠诱发疼痛行为（热诱导的伤害感受和痛觉过敏）和自发性疼痛行为（福尔马林疼痛）的影响。采用不可预测的慢性轻度应激（UCMS）范式来建立经典的抑郁模型。通过蔗糖偏好测试、旷场测试和高架十字迷宫测试评估情绪行为。结果表明，与非抑郁动物相比，抑郁大鼠在正常和完全弗氏佐剂（CFA）诱导的慢性疼痛条件下，对有害热刺激的耐受性总是更强。有趣的是，与未接受 UCMS 的大鼠相比，暴露于 UCMS 的大鼠福尔马林注射引起的自发性疼痛行为明显增强。系统给予抗抑郁药氟西汀可使抑郁动物的疼痛行为显著恢复正常水平。另一个发现是，炎症大鼠即使没有暴露于 UCMS，也往往表现出抑郁样行为。这些结果表明，抑郁对刺激引起的疼痛和自发性疼痛可能有不同的影响，前者减轻，后者加重。
本研究通过证实暴露于慢性轻度应激的大鼠对实验刺激的疼痛敏感性降低，但持续性疼痛的强度增加，为刺激引起的疼痛和自发性疼痛提供了证据，证明抑郁可能有不同的影响。这可能有助于进一步理解临床抑郁症和慢性疼痛之间复杂的关系。
