Brain, behavior, and immunity
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Brain Behav. Immun. · Nov 2010
Involvement of the peripheral sensory and sympathetic nervous system in the vascular endothelial expression of ICAM-1 and the recruitment of opioid-containing immune cells to inhibit inflammatory pain.
Endogenous opioids are known to be released within certain brain areas following stressful stimuli. Recently, it was shown that also leukocytes are a potential source of endogenously released opioid peptides following stress. They activate sensory neuron opioid receptors and result in the inhibition of local inflammatory pain. ⋯ The selective degeneration of sensory or sympathetic nerve fibers attenuated the enhanced expression of vascular endothelial ICAM-1 after intraplantar (i.pl.) FCA and abolished endogenous opioid peptide-mediated peripheral analgesia. Our results suggest that, during localized inflammatory pain, peripheral sensory and sympathetic nerve fibers augment the expression of vascular endothelial ICAM-1 simultaneously with the increased recruitment of opioid peptide-containing leukocytes which consequently promotes the endogenous opioid peptide-mediated inhibition of inflammatory pain. They support existing evidence about a close link between the nervous and the immune system.
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Brain Behav. Immun. · Oct 2010
Elevated macrophage migration inhibitory factor (MIF) is associated with depressive symptoms, blunted cortisol reactivity to acute stress, and lowered morning cortisol.
Macrophage Migration Inhibitory Factor (MIF) is a proinflammatory cytokine produced by leukocytes and the secretory cells of the HPA axis. Remarkably, glucocorticoids (GC) induce leukocyte MIF secretion, while MIF renders leukocytes insensitive to the anti-inflammatory effects of glucocorticoids. In light of reported associations between dysphoric states, increased inflammatory activity, and reduced GC sensitivity, the current study investigated the association between MIF, loneliness and depressive symptoms. ⋯ The observed association between HPA function and MIF remained robust after adjustment for depressive symptoms, and demographic, anthropomorphic, and behavioural factors. High levels of depressive symptoms were likewise associated with lower morning cortisol, but this association became non-significant after adjustment for MIF. MIF may be an important neuro-immune mediator linking depressive symptoms with inflammation and HPA dysregulation.
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Brain Behav. Immun. · Oct 2010
Involvement of microglial P2X7 receptors and downstream signaling pathways in long-term potentiation of spinal nociceptive responses.
Tetanic stimulation of the sciatic nerve (TSS) produces long-term potentiation (LTP) of C-fiber-evoked field potentials in the spinal cord. This potentiation is considered to be a substrate for long-lasting sensitization in the spinal pain pathway. Because microglia have previously been shown to regulate the induction of spinal LTP, we hypothesize that P2X7 receptors (P2X7R), which are predominantly expressed in microglia and participate in the communication between microglia and neurons, may play a role in this induction. ⋯ Further, pre-administration of BBG inhibited increased expression of the microglial marker Iba-1, phosphorylated p38 (p-p38), interleukin 1β (IL-1β) and GluR1 following TSS. Pre-administration of the IL-1 receptor antagonist (IL-1ra) blocked both the induction of spinal LTP and the up-regulation of GluR1. These results suggest that microglial P2X7Rs and its downstream signaling pathways play a pivotal role in the induction of spinal LTP and persistent pain induced by TSS.
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Brain Behav. Immun. · Oct 2010
Freewheel training decreases pro- and increases anti-inflammatory cytokine expression in mouse intestinal lymphocytes.
Intestinal inflammation and inflammatory bowel diseases (IBD) may occur due to imbalances in pro- and anti-inflammatory cytokines. Long-term exercise reduces the risk for IBD. The purpose of this study was to determine the effect of long-term wheel running in healthy mice on intestinal lymphocyte (IL) expression of pro- and anti-inflammatory cytokine proteins. ⋯ A single exposure to intense aerobic treadmill exercise increased pro-(TNF-α) and anti-(IL-10) inflammatory cytokine and pro-apoptotic protein (caspase 3) expression in IL. The percent of early and late apoptotic, and dead IL were higher after acute exercise. Although long-term voluntary wheel running did not protect against acute exercise-induced changes in IL cytokine expression or apoptosis, there was an overall 'anti-inflammatory' effect observed as a result of wheel running in healthy mice.
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Brain Behav. Immun. · Oct 2010
T lymphocytes containing β-endorphin ameliorate mechanical hypersensitivity following nerve injury.
Neuropathic pain is a debilitating consequence of nerve injuries and is frequently resistant to classical therapies. T lymphocytes mediate adaptive immune responses and have been suggested to generate neuropathic pain. In contrast, in this study we investigated T cells as a source of opioidergic analgesic β-endorphin for the control of augmented tactile sensitivity following neuropathy. ⋯ The re-established CRF antinociception could be reversed by co-injection of an antibody against β-endorphin or an opioid receptor antagonist with limited access to the central nervous system. We propose that, in response to CRF stimulation, T lymphocytes accumulating at the injured nerves utilize β-endorphin for activation of local neuronal opioid receptors to reduce neuropathy-induced mechanical hypersensitivity. Our findings reveal β-endorphin-containing T cells as a crucial component of beneficial adaptive immune responses associated with painful peripheral nerve injuries.