The cancer-related event that is most disruptive to the cancer patient's quality of life is pain. To begin to define the mechanisms that give rise to cancer pain, we examined the neurochemical changes that occur in the spinal cord and associated dorsal root ganglia in a murine model of bone cancer. Twenty-one days after intramedullary injection of osteolytic sarcoma cells into the femur, there was extensive bone destruction and invasion of the tumor into the periosteum, similar to that found in patients with osteolytic bone cancer. In the spinal cord, ipsilateral to the cancerous bone, there was a massive astrocyte hypertrophy without neuronal loss, an expression of dynorphin and c-Fos protein in neurons in the deep laminae of the dorsal horn. Additionally, normally non-noxious palpation of the bone with cancer induced behaviors indicative of pain, the internalization of the substance P receptor, and c-Fos expression in lamina I neurons. The alterations in the neurochemistry of the spinal cord and the sensitization of primary afferents were positively correlated with the extent of bone destruction and the growth of the tumor. This "neurochemical signature" of bone cancer pain appears unique when compared to changes that occur in persistent inflammatory or neuropathic pain states. Understanding the mechanisms by which the cancer cells induce this neurochemical reorganization may provide insight into peripheral factors that drive spinal cord plasticity and in the development of more effective treatments for cancer pain.

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Stress is generally considered to suppress the immune system and may lead to an increase in the occurrence of disease in the presence of a pathogen. The immune system is ordinarily brought back to a baseline response level after immune challenge through homeostatic processes, in part regulated by the hypothalamic-pituitary-axis. Often, findings reported from various studies investigating the effects of stress on the immune system are conflicting and difficult to reconcile into a cohesive and comprehensible set of universally applicable theories. These discrepancies may be partly explained by the types and durations of the stressors, the aspect(s) of immune system measured, genetics, and social status. A particular stressor may enhance cell-mediated immune responses while suppressing humoral responses or vice versa, thus disrupting the balance between these components of the immune system. How farm animals perceive their environment depends not only on traditional environmental stressors (e.g., heat, cold, humidity, pollutants), but also on aspects of their social environment. Dominant animals may have enhanced immune activation, whereas subordinates have suppression of the same immune component in response to the same stressor. This could explain why individual animals within a group respond differently to stressors and disease challenges. A better understanding of the consequences and complex interactions between social and environmental stressors for innate and adaptive immune traits must be developed so we can more fully understand the effects of stress on immunity in livestock. Once these complex relationships are better understood, more effective interventions can be designed to improve animal health and well-being.

Little is known about the participation of beta chemokines in inflammatory processes within the central nervous system. The release of three of these peptides (macrophage inflammatory protein [MIP]-1alpha, MIP-1beta, and monocyte chemoattractant protein-1) from human fetal microglial cell and astrocyte cultures was assessed following stimulation by lipopolysaccharide, interleukin-1beta, and tumor necrosis factor-alpha. Although striking differences were found between these two types of glial cells in their responsiveness to lipopolysaccharide and cytokines, both microglia and astrocytes produced all three beta chemokines. Only microglial cells, however, demonstrated an increased migratory response to the beta chemokines. The results of this in vitro study suggest that beta chemokines may play an important role in the trafficking of mononuclear phagocytes within the brain.