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Human cytomegalovirus (CMV) infection is asymptomatic in immunocompetent individuals. However, it can lead to disease in immunodeficient population. Little is known of the mechanisms underlying the pathogenicity of the virus. We investigated the impact of CMV infection on mouse nervous system. Peripheral nerves but not spinal cord was permissive to MCMV during acute infection. Activated CD8 T cells, monocytes/macrophages and cytokine expression were increased in the blood and sciatic nerves of infected mice, which exhibited transient sensory dysfunction. This study indicates that systemic MCMV infection leads to a dissemination of MCMV into peripheral nerves, which is associated with a local inflammation but not nerve tissue damage in the acute phase.
Learn More >Persistent post-surgical pain (PPSP) is a chronic pain condition, often with neuropathic features, that occurs in approximately 20% of children who undergo surgery. The biological basis of PPSP has not been elucidated. Anesthetic drugs can have lasting effects on the developing nervous system, although the clinical impact of this phenomenon is unknown. Here, we used a mouse model to test the hypothesis that early developmental exposure to isoflurane causes cellular and molecular alteration in the pain perception circuitry that causes a predisposition to chronic, neuropathic pain via a pathologic upregulation of the mammalian target of the rapamycin (mTOR) signaling pathway. Mice were exposed to isoflurane at postnatal day 7 and select cohorts were treated with rapamycin, an mTOR pathway inhibitor. Behavioral tests conducted 2 months later showed increased evidence of neuropathic pain, which did not occur in rapamycin-treated animals. Immunohistochemistry showed neuronal activity was chronically increased in the insular cortex, anterior cingulate cortex, and spinal dorsal horn, and activity was attenuated by rapamycin. Immunohistochemistry and western blotting (WB) showed a co-incident chronic, abnormal upregulation in mTOR activity. We conclude that early isoflurane exposure alters the development of pain circuits and has the potential to contribute to PPSP and/or other pain syndromes.
Learn More >The anterior cingulate cortex (ACC) is a key structure of the pain processing network. Several structural and functional alterations of this brain area have been found in migraine. In addition, altered serotonergic neurotransmission has been repeatedly implicated in the pathophysiology of migraine, although the exact mechanism is not known. Thus, our aim was to investigate the relationship between acute increase of brain serotonin (5-HT) level and the activation changes of the ACC using pharmacological challenge MRI (phMRI) in migraine patients and healthy controls.
Learn More >Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most debilitating long-term side effects in breast cancer survivors. We conducted a randomized controlled pilot trial to assess the feasibility, safety, and effects of an acupuncture intervention on CIPN in this population.
Learn More >Recent experimental research has suggested that spinal manipulative therapy (SMT) may reduce pain through modulation of the ascending pain signals and/or the central pain-regulating mechanisms. People with persistent neck pain (NP) have also been found to have disturbances in autonomic nervous system (ANS) regulation. A common way to study the ANS is to measure heart rate variability (HRV). It is not known whether deviations in HRV are related to changes in pain perception or to the treatment response to SMT. Commonly, an individual in pain will experience pain reduction when exposed to a second pain stimulus, a mechanism known as conditioned pain modulation (CPM). Patients with persistent pain have been found to have a reduced CPM reaction. It is not known whether this is predictive of treatment response to SMT. The aim of the study is to examine the effects of SMT on HRV and pain. Further, a secondary aim is to test whether a CPM test can be used to predict treatment response in a population of patients with recurrent and persistent NP.
Learn More >Neuropathic pain is a common pain condition that has a major negative impact on health-related quality of life. However, despite decades of research, it remains difficult to treat neuropathic pain. Lacosamide is a sodium-channel blocker that is efficacious in animal models of neuropathic pain. In humans, its effect in neuropathic pain is inconclusive, based on inconsistent results and very large placebo responses. Previous trials have not used patient stratification or looked for predictors for response.
Learn More >The Improving the Wellbeing of people with Opioid Treated CHronic Pain (I-WOTCH) randomised controlled trial uses a multicomponent self-management intervention to help people taper their opioid use. This approach is not widely used and its efficacy is unknown. A process evaluation alongside the trial will help to assess how the intervention was delivered, looking at the dose of intervention received and the fidelity of the delivery. We will explore how the intervention may have brought about change through the experiences of the participants receiving and the staff delivering the intervention and whether there were contextual factors involved.
Learn More >Chronic low back pain (LBP) is a leading cause of disability worldwide. Biopsychosocial rehabilitation programs have been advocated for its management, especially since the widespread acceptance of the biopsychosocial model of chronic pain. Despite extensive evidence of its short-term benefits, few studies have reported on its long-term effect and more specifically on indirect outcomes such as return to work and quality of life (QoL). The present study evaluated the long-term effect of a multidisciplinary biopsychosocial rehabilitation (MBR) program for patients with chronic LBP, for which short- and intermediate-term efficacy had been established, with an emphasis on recovering work capability.
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