Brain, behavior, and immunity
-
Brain Behav. Immun. · May 2013
Randomized Controlled TrialLow-dose endotoxin potentiates capsaicin-induced pain in man: evidence for a pain neuroimmune connection.
Despite the wealth of evidence in animals that immune activation has a key role in the development and maintenance of chronic pain, evidence to support this in humans is scant. We have sought such evidence by examining the effect of a subtle immunological stimulus, low dose intravenous endotoxin, on the allodynia, hyperalgesia, flare and pain produced by intradermal capsaicin in healthy volunteers. ⋯ These data demonstrate clinically a significant role for the neuroimmune pain connection in modifying pain, thus providing evidence that immune priming may produce pain enhancement in humans and hence offer a novel range of pharmacological targets for anti-allodynics and/or analgesics. Additionally, the simplicity of the model makes it suitable as a test-bed for novel immune-targeted pain therapeutics.
-
Brain Behav. Immun. · Mar 2013
ReviewSurgery and stress promote cancer metastasis: new outlooks on perioperative mediating mechanisms and immune involvement.
Surgery for the removal of a primary tumor presents an opportunity to eradicate cancer or arrest its progression, but is also believed to promote the outbreak of pre-existing micrometastases and the initiation of new metastases. These deleterious effects of surgery are mediated through various mechanisms, including psychological and physiological neuroendocrine and paracrine stress responses elicited by surgery. In this review we (i) describe the many risk factors that arise during the perioperative period, acting synergistically to make this short timeframe critical for determining long-term cancer recurrence, (ii) present newly identified potent immunocyte populations that can destroy autologous tumor cells that were traditionally considered immune-resistant, thus invigorating the notion of immune-surveillance against cancer metastasis, (iii) describe in vivo evidence in cancer patients that support a role for anti-cancer immunity, (iv) indicate neuroendocrine and paracrine mediating mechanisms of stress- and surgery-induced promotion of cancer progression, focusing on the prominent role of catecholamines and prostaglandins through their impact on anti-cancer immunity, and through direct effects on the malignant tissue and its surrounding, (v) discuss the impact of different anesthetic approaches and other intra-operative procedures on immunity and cancer progression, and (vi) suggest prophylactic measures against the immunosuppressive and cancer promoting effects of surgery.
-
Brain Behav. Immun. · Feb 2013
ReviewAt the extreme end of the psychoneuroimmunological spectrum: delirium as a maladaptive sickness behaviour response.
Delirium is a common and severe neuropsychiatric syndrome characterised by acute deterioration and fluctuations in mental status. It is precipitated mainly by acute illness, trauma, surgery, or drugs. Delirium affects around one in eight hospital inpatients and is associated with multiple adverse consequences, including new institutionalisation, worsening of existing dementia, and death. ⋯ We discuss inflammatory and stress-related triggers of delirium in the context of new animal models that allow us to dissect some aspects of the mechanisms underpinning these episodes. We discuss some differences between the sickness behaviour syndrome model and delirium in the context of the complexity in the latter due to other factors such as prior pathology, psychological stress and drug effects. We conclude that, with appropriate caveats, the study of sickness behaviour in the vulnerable brain offers a promising route to uncover the mechanisms of this common and serious unmet medical need.
-
Brain Behav. Immun. · Jan 2013
Strain influences on inflammatory pathway activation, cell infiltration and complement cascade after traumatic brain injury in the rat.
Increasing evidence suggests that genetic background affects outcome of traumatic brain injuries (TBI). Still, there is limited detailed knowledge on what pathways/processes are affected by genetic heterogeneity. The inbred rat strains DA and PVG differ in neuronal survival following TBI. ⋯ A stronger activation of the complement system in DA was associated with higher cerebrospinal fluid levels of neurofilament-light, a biomarker for nerve/axonal injury. In summary, we demonstrate substantial differences between DA and PVG rats in activation of inflammatory pathways; in particular, immune cell influx and complement activation associated with neuronal/axonal injury after TBI. These findings suggest genetic influences acting on inflammatory activation to be of importance in TBI and motivate further efforts using experimental forward genetics to identify genes/pathways that affect outcome.
-
Brain Behav. Immun. · Jan 2013
Impairment of lithium chloride-induced conditioned gaping responses (anticipatory nausea) following immune system stimulation with lipopolysaccharide (LPS) occurs in both LPS tolerant and LPS non-tolerant rats.
Anticipatory nausea is a classically conditioned response to a context that has been previously paired with toxin-induced nausea and/or vomiting. When injected with a nausea-inducing drug, such as lithium chloride (LiCl), rats will show a distinctive conditioned gaping response that has been suggested to be an index of nausea. Previous studies have found that immune system activation with an endotoxin, such as lipopolysaccharide (LPS), attenuates LiCl-induced conditioned gaping in rats. ⋯ Gaping responses were attenuated in rats treated with LPS in both the LPS tolerant and LPS non-tolerant groups. There were significant negative correlations between spleen weight as well as spleen/body weight ratios, and levels of conditioned gaping responses in LiCl treated rats, but not control rats. These results show that LPS interferes with learning/memory in the anticipatory nausea paradigm in rats that are both LPS tolerant and LPS non-tolerant.