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Neuropathic pain is a challenging clinical problem and remains difficult to treat. Altered gene expression in peripheral sensory nerves and neurons due to nerve injury is well documented and contributes critically to the synaptic plasticity in the spinal cord and the initiation and maintenance of chronic pain. However, our understanding of the epigenetic mechanisms regulating the transcription of pro-nociceptive (e.g., NMDA receptors and α2δ-1) and antinociceptive (e.g., potassium channels and opioid and cannabinoid receptors) genes are still limited. In this review, we summarize recent studies determining the roles of histone modifications (including methylation, acetylation, and ubiquitination), DNA methylation, and noncoding RNAs in neuropathic pain development. We review the epigenetic writer, reader, and eraser proteins that participate in the transcriptional control of the expression of key ion channels and neurotransmitter receptors in the dorsal root ganglion after traumatic nerve injury, which is commonly used as a preclinical model of neuropathic pain. A better understanding of epigenetic reprogramming involved in the transition from acute to chronic pain could lead to the development of new treatments for neuropathic pain.
Learn More >Worldwide the use of opioids, both doctor-prescribed and illicit, has increased. In most countries, opioids are first prescribed by general practitioners (GPs). Identifying factors that influence GPs' opioid prescription decision-making may help reduce opioid misuse and overuse. We performed a systematic review to gain insight into GP attitudes towards opioid prescription and to identify possible solutions to promote changes in the field of primary care.
Learn More >Bleeding is a potential complication after neuraxial and peripheral nerve blocks. The risk is increased in patients on antiplatelet and anticoagulant drugs. This joint guideline from the European Society of Anaesthesiology and Intensive Care and the European Society of Regional Anaesthesia aims to provide an evidence-based set of recommendations and suggestions on how to reduce the risk of antithrombotic drug-induced haematoma formation related to the practice of regional anaesthesia and analgesia.
Learn More >Clinically focused interventions for people living with pain, such as health professional education, clinical decision support systems, prescription drug monitoring programs, and multidisciplinary care to support opioid tapering, have all been promoted as important solutions to the North American opioid crisis. Yet none have so far delivered substantive beneficial opioid-related population health outcomes. In fact, while total opioid prescribing has leveled off or reduced in many jurisdictions, population-level harms from opioids have continued to increase dramatically. We attribute this failure partly to a poor recognition of the epistemic and ethical complexities at the interface of clinical and population health. We draw on a framework of knowledge networks in wicked problems to identify 3 strategies to help navigate these complexities: (1) designing and evaluating clinically focused interventions as complex interventions, (2) reformulating evidence to make population health dynamics apparent, and (3) appealing to the inseparability of facts and values to support decision-making in uncertainty. We advocate that applying these strategies will better equip clinically focused interventions as complements to structural and public health interventions to achieve the desired beneficial population health effects. (. 2022;112(S1):S56-S65. https://doi.org/10.2105/AJPH.2021.306500).
Learn More >Sterile water injections can provide effective pain relief during childbirth, particularly for low back pain related to childbirth. However, the pain associated administering the injections can negatively impact women's impressions of the procedure. It may discourage women from considering repeat doses despite the quality of analgesia experienced. Determining strategies to reduce the pain related to the administration of sterile water injections would improve the acceptability of the technique. Therefore, the aim of this study was to evaluate the effect of topical local anesthesia on the pain associated with administration of sterile water injections.
Learn More >Sedentary lifestyle, chronic disease, or microgravity can cause muscle deconditioning that then has an impact on other physiological systems. An example is the nervous system, which is adversely affected by decreased physical activity resulting in increased incidence of neurological problems such as chronic pain. We sought to better understand how this might occur by conducting RNA sequencing experiments on muscle biopsies from human volunteers in a 5-week bed-rest study with an exercise intervention arm. We also used a computational method for examining ligand-receptor interactions between muscle and human dorsal root ganglion (DRG) neurons, the latter of which play a key role in nociception and are generators of signals responsible for chronic pain. We identified 1352 differentially expressed genes (DEGs) in bed rest subjects without an exercise intervention but only 132 DEGs in subjects with the intervention. Among 591 upregulated muscle genes in the no intervention arm, 26 of these were ligands that have receptors that are expressed by human DRG neurons. We detected a specific splice variant of one of these ligands, placental growth factor (PGF), in deconditioned muscle that binds to neuropilin 1, a receptor that is highly expressed in DRG neurons and known to promote neuropathic pain. We conclude that exercise intervention protects muscle from deconditioning transcriptomic changes, and prevents changes in the expression of ligands that might sensitize DRG neurons, or act on other cell types throughout the body. Our work creates a set of actionable hypotheses to better understand how deconditioned muscle may influence the function of sensory neurons that innervate the entire body.
Learn More >To evaluate the effectiveness of Δ9-tetrahydrocannabinol (dronabinol, DRO), as an add-on treatment in patients with refractory chronic pain (CP).
Learn More >While widely used for the treatment of chronic pelvic pain, limited data exists on efficacy of gabapentin, especially in the subgroup of women suffering from chronic pelvic pain without a known diagnosis, such as endometriosis.
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