Are the emergence of affective disturbances in neuropathic pain states contingent on supraspinal neuroinflammation?

Fiore, Nathan T.; Austin, Paul J.

doi:10.1016/j.bbi.2016.04.012

Cited by 68 publications

(64 citation statements)

References 259 publications

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“…Accumulating evidence has suggested the key role of neuroinflammation mediated by microglia in linking neuropathic pain and depression (Burke et al, 2014; Fiore and Austin, 2016). It is reported that pro-inflammatory cytokines led to hyperalgesia (Schiavuzzo et al, 2015); meanwhile, pro-inflammatory cytokines also induced depressive-like behaviors in animals (Norman et al, 2010); In human studies, pro-inflammatory cytokines such as TNF-α and IL-1β are increased in the cerebrospinal fluid and blood in patients with chronic neuropathic pain (Alexander et al, 2005), suggesting a critical role of M1-mediated neuroinflammation in this disorder.…”

Section: Discussionmentioning

confidence: 99%

Spared Nerve Injury Increases the Expression of Microglia M1 Markers in the Prefrontal Cortex of Rats and Provokes Depression-Like Behaviors

et al. 2017

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Pain and depression are frequently co-existent in clinical practice, yet the underlying mechanisms remain largely to be determined. Microglia activation and subsequent pro-inflammatory responses play a crucial role in the development of neuropathic pain and depression. The process of microglia polarization to the pro-inflammatory M1 or anti-inflammatory M2 phenotypes often occurs during neuroinflammation. However, it remains unclear whether M1/M2 microglia polarization is involved in the neuropathic pain induced by spared nerve injury (SNI). In the present study, the mechanical withdrawal threshold, forced swim test, sucrose preference test, and open field test were performed. The levels of microglia markers including ionized calcium-binding adaptor molecule 1 (Iba1), cluster of differentiation 11b (CD11b), M1 markers including CD68, inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), IL-6, tumor necrosis factor-a (TNF-α), 8-hydroxy-2-deoxyguanosine (8-OH-dG), and M2 markers including CD206, arginase 1 (Arg1), IL-4 in the prefrontal cortex were determined on day 14 after SNI. The results showed that SNI produced mechanical allodynia and depressive-like behaviors, and also increased the expressions of microglia markers (Iba1, CD11b) and M1 markers (CD68, iNOS, IL-1β, TNF-α, and 8-OH-dG) in the prefrontal cortex. Notably, minocycline administration reversed these abnormalities. In addition, minocycline also promoted M2 microglia polarization as evidenced by up-regulation of CD206 and Arg1. In conclusion, data from our study suggest that SNI can lead to depression-like behaviors, while M1 polarization and consequent overproduction of pro-inflammatory cytokines plays a key role in the pathogenesis of neuropathic pain. The data furthermore indicate that modulation of inflammation by inhibition of M1 polarization could be a strategy for treatment of neuropathic pain, and might prevent the induction of neuropathic pain-induced depression symptoms.

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Section: Discussionmentioning

confidence: 99%

Spared Nerve Injury Increases the Expression of Microglia M1 Markers in the Prefrontal Cortex of Rats and Provokes Depression-Like Behaviors

et al. 2017

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“…Nerve injury results in mood disturbance associated with up-regulation of IL-1β 24 , IL-6 26 and TNF-α 56 in the PFC, and inhibition of inflammation rescues mood disturbance. Inflammatory signaling is triggered after peripheral nerve injury, which projects to the several supraspinal regions (including the PFC) via neural, humoral or cellular pathways 57 . In this study, we observed increased levels of proinflammatory cytokines of IL-6, IL-1β, TNF-α as well as anti-inflammatory cytokines of IL-4 and IL-10 in the rats with depression-like phenotype, but not rats without depression-like phenotype.…”

Section: Discussionmentioning

confidence: 99%

Alterations in the inflammatory cytokines and brain-derived neurotrophic factor contribute to depression-like phenotype after spared nerve injury: improvement by ketamine

Xie

Wang

et al. 2017

Sci Rep

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Although pain is frequently accompanied with depression, little is known about the risk factors contributing to individual differences to the comorbidity of pain and depression. In this study, we examined whether cytokines and brain-derived neurotrophic factor (BDNF) might contribute to the individual differences in the development of neuropathic pain-induced depression. Rats were randomly subjected to spared nerved ligation (SNI) or sham surgery. The SNI rats were divided into two groups by the data from depression-related behavioral tests. Rats with depression-like phenotype displayed higher levels of pro-inflammatory cytokines (e.g., interleukin (IL)-1β, IL-6) as well as imbalance of pro/anti-inflammatory cytokines compared with rats without depression-like phenotype and sham-operated rats. Levels of BDNF in the prefrontal cortex of rats with depression-like phenotype were lower than those of rats without depression-like phenotype and sham-operated rats. A single dose of ketamine ameliorated depression-like behaviors in the rats with depression-like phenotype. Interestingly, higher serum levels of IL-1β and IL-6 in the rat with depression-like phenotype were normalized after a single dose of ketamine. These findings suggest that alterations in the inflammatory cytokines and BDNF might contribute to neuropathic pain-induced depression, and that serum cytokines may be predictable biomarkers for ketamine’s antidepressant actions.

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“…A recent study using positron emission tomography–magnetic resonance imaging showed for the first time, in vivo, that the occurrence of glial activation, as measured by an increase in [ 11 C]PBR28 binding, was greater in the thalamus of patients with chronic pain as compared to controls [130]. Preclinical research involving nerve injury models have shown that chronic pain evokes anatomically specific neuroinflammation in brain regions that is causally linked to anxiety and depressive-like symptoms [131]. Specifically, nerve injury elicits the production of pro-inflammatory cytokines both in the periphery and centrally, which can cause a reduction in BDNF (neurogenesis) and glucocorticoid receptor expression and function, and an increase in excitoxicity in brain regions that are critical for behavior regulation (i.e., hippocampus, hypothalamus, amygdala, prefrontal cortex) [131,132,133,134,135].…”

Section: Potential Neurobiological Mechanisms Underlying Comorbid mentioning

confidence: 99%

“…Preclinical research involving nerve injury models have shown that chronic pain evokes anatomically specific neuroinflammation in brain regions that is causally linked to anxiety and depressive-like symptoms [131]. Specifically, nerve injury elicits the production of pro-inflammatory cytokines both in the periphery and centrally, which can cause a reduction in BDNF (neurogenesis) and glucocorticoid receptor expression and function, and an increase in excitoxicity in brain regions that are critical for behavior regulation (i.e., hippocampus, hypothalamus, amygdala, prefrontal cortex) [131,132,133,134,135]. Altering the connectivity of these regions can lead to alterations in function and behavioral disturbances.…”

Section: Potential Neurobiological Mechanisms Underlying Comorbid mentioning

confidence: 99%

Mental Health Comorbidities in Pediatric Chronic Pain: A Narrative Review of Epidemiology, Models, Neurobiological Mechanisms and Treatment

et al. 2016

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Chronic pain during childhood and adolescence can lead to persistent pain problems and mental health disorders into adulthood. Posttraumatic stress disorders and depressive and anxiety disorders are mental health conditions that co-occur at high rates in both adolescent and adult samples, and are linked to heightened impairment and disability. Comorbid chronic pain and psychopathology has been explained by the presence of shared neurobiology and mutually maintaining cognitive-affective and behavioral factors that lead to the development and/or maintenance of both conditions. Particularly within the pediatric chronic pain population, these factors are embedded within the broader context of the parent–child relationship. In this review, we will explore the epidemiology of, and current working models explaining, these comorbidities. Particular emphasis will be made on shared neurobiological mechanisms, given that the majority of previous research to date has centered on cognitive, affective, and behavioral mechanisms. Parental contributions to co-occurring chronic pain and psychopathology in childhood and adolescence will be discussed. Moreover, we will review current treatment recommendations and future directions for both research and practice. We argue that the integration of biological and behavioral approaches will be critical to sufficiently address why these comorbidities exist and how they can best be targeted in treatment.

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Are the emergence of affective disturbances in neuropathic pain states contingent on supraspinal neuroinflammation?

Cited by 68 publications

References 259 publications

Spared Nerve Injury Increases the Expression of Microglia M1 Markers in the Prefrontal Cortex of Rats and Provokes Depression-Like Behaviors

Spared Nerve Injury Increases the Expression of Microglia M1 Markers in the Prefrontal Cortex of Rats and Provokes Depression-Like Behaviors

Alterations in the inflammatory cytokines and brain-derived neurotrophic factor contribute to depression-like phenotype after spared nerve injury: improvement by ketamine

Mental Health Comorbidities in Pediatric Chronic Pain: A Narrative Review of Epidemiology, Models, Neurobiological Mechanisms and Treatment

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