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

Liu, Yan; Yang, Liu; Yu, Jin; Zhang, Yu‐Qiu

doi:10.1016/j.physbeh.2015.07.004

Cited by 22 publications

(24 citation statements)

References 58 publications

(80 reference statements)

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“…In the pain literature, both SDS and CVS can induce heterogeneous responses. SDS has been reported to produce no alterations in algesic response ( Li et al, 2014 ; Liu et al, 2015 ), hypoalgesia ( Rodgers and Shepherd, 1989 ; Tramullas et al, 2012 ), and hyperalgesia ( Sawicki et al, 2018 ). Similarly CVS has produced no difference ( Liu et al, 2017 ), hypoalgesia ( Shi et al, 2010 ) and hyperalgesia ( Gamaro et al, 2014 ; Lomazzo et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

The Effects of Chronic Stress on Migraine Relevant Phenotypes in Male Mice

Kaufmann

Brennan

2018

Front. Cell. Neurosci.

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Migraine is a disabling neurological disorder affecting 12% of the world’s population. Stress is a major reported trigger and exacerbator of migraine. We evaluated the effects of two chronic stress paradigms on migraine relevant phenotypes in male C57Bl/6 mice.Methods: Fifty six mice were used in a 14 day social defeat stress (SDS) and twenty three mice were used in a 40 day chronic variable stress (CVS) paradigm. Anxiety measures were evaluated using the open field and elevated plus maze (EPM) tests. Migraine relevant phenotypes were evaluated using the nitroglycerin (NTG) and cortical spreading depression (CSD) models.Results: Stress sensitive SDS mice and chronically stressed CVS mice showed decreased exploration in the open field and reduced time spent in the open arms of the EPM compared to controls. Stress sensitive and resilient SDS mice had increased serum corticosterone levels, and stressed mice in the CVS paradigm had decreased weight gain compared to controls, providing combined behavioral and physiological evidence of a stress response. In the CVS paradigm but not the SDS paradigm, the stressed group showed a significant decrease in baseline mechanical withdrawal threshold compared to controls. All groups showed a significant reduction in withdrawal threshold after treatment with NTG, but the reduction was not larger in SDS or CVS than in controls. Interestingly, stress resilient SDS mice showed a rapid recovery from NTG effects that was not seen in other groups. No difference in CSD frequency or velocity was seen between stress and control mice in either stress paradigms.Conclusion: We observed distinct effects of stress on generalized pain response, migraine relevant pain, and migraine relevant excitability. CVS but not SDS was associated with a reduced mechanical withdrawal threshold, consistent with a generalized pain response to chronic stress. Neither SDS nor CVS exacerbated phenotypes considered specifically relevant to migraine - withdrawal to NTG, and susceptibility to CSD. However, the significantly reduced response of stress resilient mice to the NTG stimulus may represent a specific migraine-resistant phenotype.

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Section: Discussionmentioning

confidence: 99%

The Effects of Chronic Stress on Migraine Relevant Phenotypes in Male Mice

Kaufmann

Brennan

2018

Front. Cell. Neurosci.

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“…Few studies have reported the effect of social defeat stress (SDS) on nociceptive behavior in mice (Liu, Yang, Yu, & Zhang, ; Rivat et al., ). The present study aimed to investigate the nociceptive behavior of mice submitted to the SDS protocol, as well as analyze possible neuroplastic changes at a molecular level in the NAc and VTA of these animals.…”

Section: Discussionmentioning

confidence: 99%

Social defeat stress induces hyperalgesia and increases truncated BDNF isoforms in the nucleus accumbens regardless of the depressive‐like behavior induction in mice

Pagliusi

Bonet

Dias

et al. 2018

Eur J of Neuroscience

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Epidemiological studies have shown a close association between pain and depression. There is evidence showing this association as patients with depression show a high chronic pain prevalence and vice versa. Considering that social stress is critical for the development of depression in humans, we used a social defeat stress (SDS) model which induces depressive-like behavior in mice. In this model, mice are exposed to an aggressor mouse for ten days, suffering brief periods of agonistic contact and long periods of sensory contact. Some mice display social avoidance, a depressive-like behavior, and are considered susceptible, while some mice do not, and are considered resilient. Thus, we investigated the nociceptive behavior of mice submitted to SDS and the neuroplastic changes in dopaminergic mesolimbic system. Our results showed that the stressed mice (resilient and susceptible) presented a higher sensitivity to pain than the control mice in chemical and mechanical tests. We also verified that susceptible mice have higher Bdnf mRNA in the VTA compared to the resilient and control mice. The stressed mice had less mature BDNF and more truncated BDNF protein in the NAc compared with control mice. Although social stress may trigger the development of depression and hyperalgesia, these two conditions may manifest independently as social stress induced hyperalgesia even in mice that did not display depressive-like behavior. Also, increased Bdnf in the VTA seems to be associated with depressive-like behavior, whereas high levels of truncated BDNF and low mature BDNF appear to be associated with hyperalgesia induced by social defeat stress.

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“…Specifically, it has yet to be established in neither clinical nor animals studies if psychological distress is a precursor (Rivat et al, 2010) to or consequence (Eccleston and Clinch, 2007) of living with chronic pain. Liu et al (2015) found that persistent inflammatory pain and social defeat stress-induced anxiety may not exacerbate one another in animal models of co-morbidity. Aizawa et al (2018) showed that the role of G protein-coupled receptor 40/free fatty acid receptor 1 is a signal for the development of chronic pain and is induced by emotional dysfunction (Aizawa et al, 2018).…”

Section: Mouse Models Of Chronic Pain and Stressmentioning

confidence: 96%

Walking the Tightrope: A Proposed Model of Chronic Pain and Stress

Lunde

Sieberg

2020

Front. Neurosci.

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Pain and stress are both phenomena that challenge an individual's homeostasis and have significant overlap in conceptual and physiological processes. Allostasis is the ability to adapt to pain and stress and maintain homeostasis; however, if either process becomes chronic, it may result in negative long-term outcomes. The negative effects of stress on health outcomes on physiology and behavior, including pain, have been well documented; however, the specific mechanisms of how stress and what quantity of stress contributes to the maintenance and exacerbation of pain have not been identified, and thus pharmacological interventions are lacking. The objective of this brief review is to: 1. identify the gaps in the literature on the impact of acute and chronic stress on chronic pain, 2. highlight future directions for stress and chronic pain research; and 3. introduce the Pain-Stress Model in the context of the current literature on stress and chronic pain. A better understanding of the connection between stress and chronic pain could provide greater insight into the neurobiology of these processes and contribute to individualized treatment for pain rehabilitation and drug development for these often comorbid conditions.

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

Cited by 22 publications

References 58 publications

The Effects of Chronic Stress on Migraine Relevant Phenotypes in Male Mice

The Effects of Chronic Stress on Migraine Relevant Phenotypes in Male Mice

Social defeat stress induces hyperalgesia and increases truncated BDNF isoforms in the nucleus accumbens regardless of the depressive‐like behavior induction in mice

Walking the Tightrope: A Proposed Model of Chronic Pain and Stress

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