Reduced sleep, stress responsivity, and female sex contribute to persistent inflammation-induced mechanical hypersensitivity in rats

Page, Gayle G.; Opp, Mark R.; Kozachik, Sharon

doi:10.1016/j.bbi.2014.02.013

Cited by 15 publications

(18 citation statements)

References 73 publications

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“…Changes in higher-order functions such as anxiety or depression are critical components of pain phenotypes, especially in the context of a chronic pain state (196,197). Studies in animal models (99,198,199) and in vivo positron emission tomography (PET) associated with magnetic resonance imaging (MRI) in humans (200,201) are consistent with the fact that chronic pain states lead to an alteration of glial function in the brain.…”

Section: Supraspinal Areasmentioning

confidence: 80%

Neuraxial Cytokines in Pain States

et al. 2020

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A high-intensity potentially tissue-injuring stimulus generates a homotopic response to escape the stimulus and is associated with an affective phenotype considered to represent pain. In the face of tissue or nerve injury, the afferent encoding systems display robust changes in the input-output function, leading to an ongoing sensation reported as painful and sensitization of the nociceptors such that an enhanced pain state is reported for a given somatic or visceral stimulus. Our understanding of the mechanisms underlying this non-linear processing of nociceptive stimuli has led to our appreciation of the role played by the functional interactions of neural and immune signaling systems in pain phenotypes. In pathological states, neural systems interact with the immune system through the actions of a variety of soluble mediators, including cytokines. Cytokines are recognized as important mediators of inflammatory and neuropathic pain, supporting system sensitization and the development of a persistent pathologic pain. Cytokines can induce a facilitation of nociceptive processing at all levels of the neuraxis including supraspinal centers where nociceptive input evokes an affective component of the pain state. We review here several key proinflammatory and anti-inflammatory cytokines/chemokines and explore their underlying actions at four levels of neuronal organization: (1) peripheral nociceptor termini; (2) dorsal root ganglia; (3) spinal cord; and (4) supraspinal areas. Thus, current thinking suggests that cytokines by this action throughout the neuraxis play key roles in the induction of pain and the maintenance of the facilitated states of pain behavior generated by tissue injury/inflammation and nerve injury.

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Section: Supraspinal Areasmentioning

confidence: 80%

Neuraxial Cytokines in Pain States

et al. 2020

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“…Finally, it is important to point out that, compared to other inbred and outbred strains, the F344 rat strain is a high stress responsive strain both emotionally (Carobrez and Bertoglio, 2005) and in HPA axis responsiveness to stress (Page et al., 2014, Sternberg et al., 1992). Given that other studies of social defeat have largely used Wistar (e.g., Kieran et al., 2010, Kinn et al., 2008, Rygula et al., 2005, Rygula et al., 2008) or Sprague Dawley (Andre et al., 2005, Becker et al., 2008) rats as intruders, it will be important to validate these findings in other strains.…”

Section: Discussionmentioning

confidence: 99%

Sex differences in sleep, anhedonia, and HPA axis activity in a rat model of chronic social defeat

Page

Opp

Kozachik

2016

Neurobiology of Stress

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Repeated bouts of a major stressor such as social defeat are well known to induce a depression phenotype in male rats. Despite strong evidence and acknowledgement that women have a two-fold lifetime greater risk of developing major depression compared to men, the inclusion of female rats in studies employing social defeat are very rare; their absence is attributed to less aggressive interactions. This study sought to compare in male and female rats the impact of repeated social defeat, three times per week for four weeks, on the development of changes in sleep architecture and continuity, sucrose preference as a measure of anhedonia, changes in body weight, and basal plasma corticosterone levels. We found significant reductions in rapid eye movement sleep (REMS) during the light phase in both females and males, and significant increases in numbers of vigilance state transitions during the early dark phase in females but not in males. Additionally, females exhibited significantly greater reductions in sucrose intake than males. On the other hand, no sex differences in significantly elevated basal corticosterone levels were evident, and only the males exhibited changes in body weight. Taken together these findings suggest that the inclusion of female rats in studies of social defeat may offer greater insights in studies of stress and depression.

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“…Neuropathic pain is a complex pain state caused by dysfunction of the somatosensory nervous system, starting from primary nociceptive afferent axons up to various supraspinal brain regions. Most cases of neuropathic pain are chronic and patients often develop comorbidities such as anxiety, depression and sleep disturbance, which in turn contribute to or exacerbate pain (Nicholson and Verma, 2004;Page et al, 2014). Several experimental rodent models, such as spared nerve injury (SNI), have been used to study neuropathic pain and its comorbidities (Campbell and Meyer, 2006).…”

Section: Introductionmentioning

confidence: 99%

Spinal versus brain microglial and macrophage activation traits determine the differential neuroinflammatory responses and analgesic effect of minocycline in chronic neuropathic pain

Wang

Piirainen

et al. 2016

Brain, Behavior, and Immunity

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Substantial evidence indicates involvement of microglia/macrophages in chronic neuropathic pain. However, the temporal-spatial features of microglial/macrophage activation and their pain-bound roles remain elusive. Here, we evaluated microglia/macrophages and the subtypes in the lumbar spinal cord (SC) and prefrontal cortex (PFC), and analgesic-anxiolytic effect of minocycline at different stages following spared nerve injury (SNI) in rats. While SNI enhanced the number of spinal microglia/macrophages since post-operative day (POD)3, pro-inflammatory MHCII spinal microglia/macrophages were unexpectedly less abundant in SNI rats than shams on POD21. By contrast, less abundant anti-inflammatory CD172a (SIRPα) microglia/macrophages were found in the PFC of SNI rats. Interestingly in naïve rats, microglial/macrophage expression of CD11b/c, MHCII and MHCII/CD172a ratio were higher in the SC than the cortex. Consistently, multiple immune genes involved in anti-inflammation, phagocytosis, complement activation and M2 microglial/macrophage polarization were upregulated in the spinal dorsal horn and dorsal root ganglia but downregulated in the PFC of SNI rats. Furthermore, daily intrathecal minocycline treatment starting from POD0 for two weeks alleviated mechanical allodynia most robustly before POD3 and attenuated anxiety on POD9. Although minocycline dampened spinal MHCII microglia/macrophages until POD13, it failed to do so on cortical microglia/macrophages, indicating that dampening only spinal inflammation may not be enough to alleviate centralized pain at the chronic stage. Taken together, our data provide the first evidence that basal microglial/macrophage traits underlie differential region-specific responses to SNI and minocycline treatment, and suggest that drug treatment efficiently targeting not only spinal but also brain inflammation may be more effective in treating chronic neuropathic pain.

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Reduced sleep, stress responsivity, and female sex contribute to persistent inflammation-induced mechanical hypersensitivity in rats

Cited by 15 publications

References 73 publications

Neuraxial Cytokines in Pain States

Neuraxial Cytokines in Pain States

Sex differences in sleep, anhedonia, and HPA axis activity in a rat model of chronic social defeat

Spinal versus brain microglial and macrophage activation traits determine the differential neuroinflammatory responses and analgesic effect of minocycline in chronic neuropathic pain

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