Brain, behavior, and immunity
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Brain Behav. Immun. · Oct 2011
ReviewPeripheral immune contributions to the maintenance of central glial activation underlying neuropathic pain.
Recent evidence implicates an adaptive immune response in the central nervous system (CNS) mechanisms of neuropathic pain. This review identifies how neuropathic pain alters CNS immune privilege to facilitate T cell infiltration. ⋯ In this way, T cells may contribute to the maintenance of neuropathic pain through pro-inflammatory interactions with microglia and by facilitating the activation of astrocytes in the spinal dorsal horn. Based on the evidence presented in this review, we suggest that this bidirectional, pro-inflammatory system of neurons, glia and T cells in neuropathic pain should be renamed the pentapartite synapse, and identifies the latest member as a potential disease-modifying therapeutic target.
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Brain Behav. Immun. · Oct 2011
Fatigued breast cancer survivors and gene polymorphisms in the inflammatory pathway.
Chronic fatigue (CF) in breast cancer survivors (BCSs) has been associated with increased serum C-reactive protein-levels (CRP), pro-inflammatory cytokines and cytokine gene single nucleotide polymorphisms (SNPs). Still, there are few studies on these topics, and due to small study-cohorts the possibility to adjust for other conditions related to inflammatory processes, e.g. depression, has been limited. In 302 BCSs, examined approximately four years after treatment for breast cancer stage II/III, data on high sensitivity (hs)CRP, leukocytes and mRNA interleukin (IL)1β and IL6R expression, depression and chronic fatigue were available. ⋯ In the subset of persistent fatigued and never-fatigued individuals the CRP SNP (rs3091244) was associated with hsCRP level (p=0.02). IL1β and IL6R mRNA expression levels were not related to the IL1β and IL6R genotypes. In a large cohort of BCSs the investigated SNPs in inflammation-related genes were not associated with fatigue, though subset analyses indicated an association between the CRP SNP (rs3091244) and serum hsCRP.
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Brain Behav. Immun. · Oct 2011
Neuronal NR2B-containing NMDA receptor mediates spinal astrocytic c-Jun N-terminal kinase activation in a rat model of neuropathic pain.
Spinal N-methyl d-aspartate receptor (NMDAR) plays a pivotal role in nerve injury-induced central sensitization. Recent studies suggest that NMDAR also contributes to neuron-astrocyte signaling. c-Jun N-terminal kinase (JNK) is persistently and specifically activated (indicated by phosphorylation) in spinal cord astrocytes after nerve injury and thus it is considered as a dependable indicator of pain-related astrocytic activation. NMDAR-mediated JNK activation in spinal dorsal horn might be an important form of neuron-astrocyte signaling in neuropathic pain. ⋯ Treatments targeting NMDAR-nNOS pathway also influenced interleukin-1beta expression, which further confirmed our hypothesis. Taken together, our results suggest that neuronal NMDAR-nNOS pathway could activate astrocytic JNK pathway. Excitatory neuronal transmission initiates astrocytic activation-induced neuroinflammation in this way, which contributes to nerve injury-induced neuropathic pain.
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Brain Behav. Immun. · Aug 2011
Comparative StudyNaloxone-precipitated morphine withdrawal behavior and brain IL-1β expression: comparison of different mouse strains.
The development of opioid dependence involves classical neuronal opioid receptor activation and is due in part to engagement of glia causing a proinflammatory response. Such opioid-induced glial activation occurs, at least in part, through a non-classical opioid mechanism involving Toll-like-receptor 4 (TLR4). Among the immune factors released following the opioid-glia-TLR4 interaction, interleukin-1β (IL-1β) plays a prominent role. ⋯ Gene sequence differences of IL - 1β and TLR4 genes alone did not explain the heterogeneity of dependence behavior between mouse strains. Together, these data further support the involvement of opioid-induced CNS immune signaling in dependence development. Moreover, this study demonstrated the advantages of utilizing multiple mouse strains and indicates that appropriate choice of mouse strains could enhance future research outcomes.
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Brain Behav. Immun. · Aug 2011
Microglial GRK2: a novel regulator of transition from acute to chronic pain.
Pain is a hallmark of tissue damage and inflammation promoting tissue protection and thereby contributing to repair. Therefore, transient acute pain is an important feature of the adaptive response to damage. However, in a significant number of cases, pain persists for months to years after the problem that originally caused the pain has resolved. ⋯ This finding is clinically relevant because rodent models of chronic pain are associated with reduced cellular levels of GRK2. We propose that GRK2 is a newly discovered major player in the regulation of chronic pain. The pathways regulated by this kinase may open up new avenues for development of treatment strategies that target the cause, and not the symptoms of chronic pain.