How to study anxiety and depression in rodent models of chronic pain?

Kremer, Mélanie; Becker, Léa J.; Barrot, Michel; Yalçın, İpek

doi:10.1111/ejn.14686

Cited by 104 publications

(119 citation statements)

References 292 publications

(591 reference statements)

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“…Chronic pain is among the main causes of affective disorders. The same comorbidity among chronic pain and affective disorders is found in animal models of chronic pain [31,32]. Accordingly, anxiety and depression-like behaviors have been widely reported in the SNI model of neuropathic pain [28,[33][34][35][36][37][38][39].…”

Section: Behavioral Symptoms Associated With the Spared Nerve Injurymentioning

confidence: 69%

Behavioral, Biochemical and Electrophysiological Changes in Spared Nerve Injury Model of Neuropathic Pain

Guida¹,

Gregorio

Palazzo³

et al. 2020

IJMS

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Neuropathic pain is a pathological condition induced by a lesion or disease affecting the somatosensory system, with symptoms like allodynia and hyperalgesia. It has a multifaceted pathogenesis as it implicates several molecular signaling pathways involving peripheral and central nervous systems. Affective and cognitive dysfunctions have been reported as comorbidities of neuropathic pain states, supporting the notion that pain and mood disorders share some common pathogenetic mechanisms. The understanding of these pathophysiological mechanisms requires the development of animal models mimicking, as far as possible, clinical neuropathic pain symptoms. Among them, the Spared Nerve Injury (SNI) model has been largely characterized in terms of behavioral and functional alterations. This model is associated with changes in neuronal firing activity at spinal and supraspinal levels, and induces late neuropsychiatric disorders (such as anxious-like and depressive-like behaviors, and cognitive impairments) comparable to an advanced phase of neuropathy. The goal of this review is to summarize current findings in preclinical research, employing the SNI model as a tool for identifying pathophysiological mechanisms of neuropathic pain and testing pharmacological agent.

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Section: Behavioral Symptoms Associated With the Spared Nerve Injurymentioning

confidence: 69%

Behavioral, Biochemical and Electrophysiological Changes in Spared Nerve Injury Model of Neuropathic Pain

Guida¹,

Gregorio

Palazzo³

et al. 2020

IJMS

View full text Add to dashboard Cite

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“…Anxiety and depression are common comorbid emotional deficits that are associated with neuropathic patients that adversely affect the patient's quality of life 28 , 29 . The use of open field and elevated maze plus in the analysis of anxiety-like and depressive behaviour in rodents has been well documented 30 . The study revealed that only a high dose of bromelain was effective in reversing the anxiety-like and depressive-like behaviours.…”

Section: Discussionmentioning

confidence: 99%

Bromelain reduced pro-inflammatory mediators as a common pathway that mediate antinociceptive and anti-anxiety effects in sciatic nerve ligated Wistar rats

Bakare

Owoyele

2021

Sci Rep

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The involvement of pro-inflammatory mediators complicates the complex mechanism in neuropathic pain (NP). This study investigated the roles of bromelain against pro-inflammatory mediators as a mechanism that underpins its antinociceptive and anti-anxiety effects in the peripheral model of NP. Sixty-four male Wistar rats randomly divided into eight groups, were used for the study. A chronic constriction injury model of peripheral neuropathy was used to induce NP. Tail-immersion and von Frey filaments tests were used to assess hyperalgesia while open field and elevated plus mazes were used to assess anxiety-like behaviour. NF-кB, iNOS, nitrate, and pro-inflammatory cytokines were investigated in the plasma, sciatic nerve, and brain tissues using ELISA, spectrophotometer, and immunohistochemistry techniques after twenty-one days of treatment. Bromelain significantly (p < 0.05) improved the cardinal signs of NP and inhibited anxiety-like behaviours in ligated Wistar rats. It mitigated the increases in cerebral cortex interleukin (IL) -1β, IL-6, and PGE2 levels. Bromelain reduced NF-кB, IL-1β, IL-6, TNF-α, PGE2, and nitrate concentrations as well as the expression of iNOS in the sciatic nerve. Hence, the antinociceptive and anxiolytic effects of bromelain in the sciatic nerve ligation model of NP is in part due to its ability to reduce nitrosative and inflammatory activities.

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“…Depressive-like behaviour may require even more time to evolve 66 . Whilst some studies suggest that up to 4 months may be required before robust anxiety-behaviour is evident after injury 14,15 , other studies using similar methodology have not replicated these observations 16 , perhaps as a consequence of animal-related factors such as strain or gender 25 . To our knowledge, very few studies have explored the effect of strain on the development of emotional comorbidities after nerve injury 44 .…”

Section: Discussionmentioning

confidence: 99%

“…And despite very similar methodology, some preclinical studies show time-dependent development of anxiety-like comorbidity following nerve-injury 14,15 , while others have failed to confirm this 16 , where the only apparent differences have been animal-and facility-related factors, like strain, gender and laboratory environment. A broad range of studies have now compared different inbred and outbred rat strains on parameters related to pain, anxiety and depression (examples: [17][18][19][20][21][22][23][24] ), but surprisingly, to our knowledge, very few have explored the effects of strain/animal genetics on the development of emotional comorbidities following injury, despite assumptions that this may be a relevant factor to explain the variability in the field 25 .…”

mentioning

confidence: 99%

The influence of rat strain on the development of neuropathic pain and comorbid anxio-depressive behaviour after nerve injury

Hestehave

Abelson

Pedersen

et al. 2020

Sci Rep

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Back-translating the clinical manifestations of human disease burden into animal models is increasingly recognized as an important facet of preclinical drug discovery. We hypothesized that inbred rat strains possessing stress hyper-reactive-, depressive- or anxiety-like phenotypes may possess more translational value than common outbred strains for modeling neuropathic pain. Rats (inbred: LEW, WKY, F344/ICO and F344/DU, outbred: Crl:SD) were exposed to Spared Nerve Injury (SNI) and evaluated routinely for 6 months on behaviours related to pain (von Frey stimulation and CatWalk-gait analysis), anxiety (elevated plus maze, EPM) and depression (sucrose preference test, SPT). Markers of stress reactivity together with spinal/brain opioid receptor expression were also measured. All strains variously developed mechanical allodynia after SNI with the exception of stress-hyporesponsive LEW rats, despite all strains displaying similar functional gait-deficits after injury. However, affective changes reflective of anxiety- and depressive-like behaviour were only observed for F344/DU in the EPM, and for Crl:SD in SPT. Although differences in stress reactivity and opioid receptor expression occurred, overall they were relatively unaffected by SNI. Thus, anxio-depressive behaviours did not develop in all strains after nerve injury, and correlated only modestly with degree of pain sensitivity or with genetic predisposition to stress and/or affective disturbances.

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How to study anxiety and depression in rodent models of chronic pain?

Abstract: Pain is a multidimensional and subjective experience which is considered as a debilitating disease when it becomes chronic. Chronic pain does indeed affect various aspects of the patient's quality of life, including mood, sleep and cognitive processes (

Cited by 104 publications

References 292 publications

Behavioral, Biochemical and Electrophysiological Changes in Spared Nerve Injury Model of Neuropathic Pain

Behavioral, Biochemical and Electrophysiological Changes in Spared Nerve Injury Model of Neuropathic Pain

Bromelain reduced pro-inflammatory mediators as a common pathway that mediate antinociceptive and anti-anxiety effects in sciatic nerve ligated Wistar rats

The influence of rat strain on the development of neuropathic pain and comorbid anxio-depressive behaviour after nerve injury

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