Depression Shows Divergent Effects on Evoked and Spontaneous Pain Behaviors in Rats

Abstract

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 non-depressed 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 depressivelike 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. Perspective: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.

Pain and depression comorbidity: A preclinical perspective

“…However, these animals showed increased response in formalin-induced spontaneous nociceptive behaviors [65, 66]. The changes in depressed animals were prevented by chronic antidepressant fluoxetine treatment [65]. In another study, the same authors reported that CUMS-operated animals showed significantly higher pain threshold to thermal stimulus (plantar test) and mechanical stimulus (von Frey test in CCI rats), extending their previous findings [67].…”

“…In two studies from the same lab that employed different depression models (CUMS and OB), depressed animals demonstrated higher pain threshold to thermal stimuli either under normal condition or under CFA-induced chronic pain condition. However, these animals showed increased response in formalin-induced spontaneous nociceptive behaviors [65, 66]. The changes in depressed animals were prevented by chronic antidepressant fluoxetine treatment [65].…”

Persistent, comorbid pain and anxiety can be uncoupled in a mouse model

“…Additionally, food deprivation and social inequality stress decreased the pain perception in formalin-inflammatory pain [51]. The contrary reports included that formalin-inflammatory rats with CMS showed greater nociceptive responses than those without CMS [50]. Rats exposed to chronic restraint stress [52] or SD stress [8,53] developed allodynia or hyperalgesia.…”

“…Animal research also incorporated pain-increasing and pain-inhibiting influences of anxiety or depression-like states. Rats subjected to CMS exhibited increased nociceptive thresholds in normal, CFA-inflammation and spinal nerve ligated (SNL)-neuropathic pain conditions [48][49][50]. Additionally, food deprivation and social inequality stress decreased the pain perception in formalin-inflammatory pain [51].…”

Validation of an air-puff passive-avoidance paradigm for assessment of aversive learning and memory in rat models of chronic pain

“…Clinical and preclinical studies have demonstrated that altered sensitivity to noxious stimuli, or increased incidence and severity of chronic pain, is associated with a large number of disorders of the central nervous system, including depression Dworkin et al, 1995;Klauenberg et al, 2008;Shi et al, 2010a;Shi et al, 2010b;Terhaar et al, 2010), anxiety disorders (Asmundson and Katz, 2009;Finn et al, 2006;Geuze et al, 2007;Ploghaus et al, 2001;Rivat et al, 2010), multiple sclerosis (Kenner et al, 2007;Olechowski et al, 2009;Solaro et al, 2003) and others. Thus, a passive-avoidance paradigm using air-puff in place of noxious foot-shock may also be preferable for assessment of aversive learning and memory in rodent models of these disorders.…”