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Inflammation constitutes both positive and negative aspects to recovery following peripheral nerve injury. Following damage to the peripheral nervous system (PNS), immune cells such as macrophages play a beneficial role in creating a supportive environment for regrowing axons by phagocytosing myelin and axonal debris. However, a prolonged inflammatory response after peripheral nerve injury has been implicated in the pathogenesis of negative symptoms like neuropathic pain. Therefore, the post-injury inflammation must be carefully controlled to prevent secondary damage while allowing for regeneration. CRYAB (also known as alphaB-crystallin/HSPB5) is a small heat shock protein that has many protective functions including an immunomodulatory role in mouse models of multiple sclerosis, spinal cord injury, and stroke. Because its expression wanes and rebounds in the early and late periods respectively after PNS damage, and CRYAB null mice with sciatic nerve crush injury display symptoms of pain, we investigated whether CRYAB is involved in the immune response following PNS injury.
Learn More >While multiple pharmacological and non-pharmacological interventions treating chronic non-specific low back pain (CLBP) are available, they have been shown to produce at best modest effects. Interventions such as repetitive transcranial magnetic stimulation (rTMS), a form of non-invasive brain stimulation, have exhibited promising results to alleviate chronic pain. However, evidence on the effectiveness of rTMS for CLBP is scarce due to limited rigorous clinical trials. Combining rTMS with motor control exercises (MCE) may help to address both central and nociceptive factors contributing to the persistence of LBP. The primary aim of this randomised controlled trial is to compare the effectiveness of a combination of rTMS and MCE to repeated rTMS sessions alone, sham rTMS and a combination of sham rTMS and MCE on pain intensity.
Learn More >Patients classified as having whiplash-associated disorder (WAD) grade II, which reflects approximately 93% of patients with WAD who are commonly managed by health care professionals, exhibit both physical (eg, pain and disability) and psychological (eg, fear of movement, anxiety, posttraumatic stress) problems that, in approximately 50% of cases, persist beyond 3 months. There is still much ongoing debate regarding factors predictive of poor recovery. The strongest associations have been found for high initial pain and disability following whiplash injury. In addition, a growing body of evidence supports the clinical importance of characteristic features, such as disturbed nociceptive processing (eg, local or general hyperalgesia to cold and mechanical stimuli), inefficient cognitions and beliefs about pain/movement/recovery, and posttraumatic stress symptoms, in the development and maintenance of physical and psychological manifestations in patients with WAD. For this reason, the field shifted away from single interventions that mainly follow a biomedical approach, such as exercise therapy and activity programs, to gold standard multimodal care (at least 2 distinct therapeutic modalities given by 1 or more health care professionals) that acknowledges the biopsychological nature of WAD. To date, there exist several multimodal care approaches to managing WAD; however, for most the efficacy has been found to be rather limited. One may argue that the limited success of some approaches can be attributed to the fact that they focused mainly on rehabilitating the physical symptoms (eg, pain, disability) rather than also the associated cognitive (eg, catastrophizing) and psychological (eg, posttraumatic stress symptoms) symptoms of the condition, leaving much room for improvement. In this article, current and previous evidence is used to explain why and how a comprehensive and multimodal treatment for people with WAD-consisting of a combination of pain neuroscience education, cognition-targeted exercise therapy, and stress management-can be applied in clinical practice.
Learn More >Little is known about the effects of sleep disturbance (SD) on clinical outcomes after spine surgery.
Learn More >With the aging population, it is clear that the demand for future chronic pain treatment modalities is at an all-time high. One of the newest treatment modalities that is gaining popularity with both practitioners and patients alike is that of regenerative medicine and the use of stem cells to treat chronic painful conditions. This article aims to distill the most recent, available data from both laboratory research and clinical trials to better illuminate the potentials for these therapies in the treatment of chronic pain.
Learn More >Chemotherapy-Induced Peripheral Neuropathy (CIPN) is a common, difficult-to-treat, and dose-limiting side effect associated with Oxaliplatin (OXA) treatment. In this study, we evaluated the effect of three antioxidants – namely N-acetylcysteine, α-lipoic acid and vitamin E – upon nociceptive parameters and antitumor efficacy of OXA in a tumor-bearing Swiss mice model. Oral treatment with antioxidants inhibited both mechanical and cold allodynia when concomitantly administrated with OXA (preventive protocol), as well as in animals with previously established CIPN (therapeutic protocol). OXA increased Reactive Oxygen Species (ROS) production and lipoperoxidation, and augmented the content of pro-inflammatory cytokines (IL-1β and TNF-α) and expression of the astrocytic marker Gfap mRNA in the spinal cord. Antioxidants decreased ROS production and lipoperoxidation, and abolished neuroinflammation in OXA-treated animals. Toll-like receptor 4 (Tlr4) and inflammasome enzyme caspase-1/11 knockout mice treated with OXA showed reduced levels of pro-inflammatory cytokines (but not oxidative stress) in the spinal cord, which were associated with resistance to OXA-induced mechanical allodynia. Lastly, antioxidants affected neither antitumor activity nor hematological toxicity of OXA in vivo. The herein presented results are provocative for further evaluation of antioxidants in clinical management of chemotherapy-induced peripheral neuropathy. Perspectives: This study reports preventive and therapeutic efficacy of orally administrated antioxidants (N-acetylcysteine, α-lipoic-acid and Vitamin-E) for alleviating oxaliplatin-induced peripheral neuropathy in tumor-bearing mice. Antioxidants' anti-nociceptive effects are associated with inhibition of ROS-dependent neuroinflammation, and occur at no detriment of OXA antitumor activity, therefore indicating a translational potential of these compounds.
Learn More >Dual enkephalinase inhibitors (DENKIs) are pain medications that indirectly activate opioid receptors and can be used as an alternative to traditional opioids. Understanding the physiology of enkephalins and their inhibitors and the pharmacology of these drugs will allow for proper clinical application for chronic pain patients in the future.
Learn More >Although millions of people are diagnosed with cancer each year, survival has never been greater thanks to early diagnosis and treatments. Powerful chemotherapeutic agents are highly toxic to cancer cells, but because they typically do not target cancer cells selectively, they are often toxic to other cells and produce a variety of side effects. In particular, many common chemotherapies damage the peripheral nervous system and produce neuropathy that includes a progressive degeneration of peripheral nerve fibers. Chemotherapy-induced peripheral neuropathy (CIPN) can affect all nerve fibers, but sensory neuropathies are the most common, initially affecting the distal extremities. Symptoms include impaired tactile sensitivity, tingling, numbness, paraesthesia, dysesthesia, and pain. Since neuropathic pain is difficult to manage, and because degenerated nerve fibers may not grow back and regain normal function, considerable research has focused on understanding how chemotherapy causes painful CIPN so it can be prevented. Due to the fact that both therapeutic and side effects of chemotherapy are primarily associated with the accumulation of reactive oxygen species (ROS) and oxidative stress, this review focuses on the activation of endogenous antioxidant pathways, especially PPARγ, in order to prevent the development of CIPN and associated pain. The use of synthetic and natural PPAR а agonists to prevent CIPN is discussed.
Learn More >This review aims to summarize interventions used in the perioperative period to reduce the development of new persistent postoperative opioid use in opioid-naïve patients.
Learn More >Because somatosensory PNS neurons, in particular nociceptors, are specially tuned to be able to detect a wide variety of both exogenous and endogenous signals, one might assume that these neurons express a greater variety of receptor genes. This assumption has not been formally tested. Because cells detect such signals via cell surface receptors, we sought to formally test the hypothesis that PNS neurons might express a broader array of cell surface receptors than CNS neurons using existing single cell RNA sequencing resources from mouse. We focused our analysis on ion channels, G-protein coupled receptors (GPCRS), receptor tyrosine kinase and cytokine family receptors. In partial support of our hypothesis, we found that mouse PNS somatosensory, sympathetic and enteric neurons and CNS neurons have similar receptor expression diversity in families of receptors examined, with the exception of GPCRs and cytokine receptors which showed greater diversity in the PNS. Surprisingly, these differences were mostly driven by enteric and sympathetic neurons, not by somatosensory neurons or nociceptors. Secondary analysis revealed many receptors that are very specifically expressed in subsets of PNS neurons, including some that are unique among neurons for nociceptors. Finally, we sought to examine specific ligand-receptor interactions between T cells and PNS and CNS neurons. Again, we noted that most interactions between these cells are shared by CNS and PNS neurons despite the fact that T cells only enter the CNS under rare circumstances. Our findings demonstrate that both PNS and CNS neurons express an astonishing array of cell surface receptors and suggest that most neurons are tuned to receive signals from other cells types, in particular immune cells.
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