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High rates of chronic non-cancer pain (CNCP), concerns about adverse effects including dependence among those prescribed potent pain medicines, the recent evidence supporting active rather than passive management strategies and a lack of funding for holistic programme have resulted in challenges around decision making for treatment among clinicians and their patients. Discrete choice experiments (DCEs) are one way of assessing and valuing treatment preferences. Here, we outline a protocol for a study that assesses patient preferences for CNCP treatment.
Learn More >Migraine is a debilitating neurological disorder involving abnormal trigeminovascular activation and sensitization. However, the underlying cellular and molecular mechanisms remain unclear.
Learn More >The Centers for Disease Control and Prevention guidelines in 2016 recommended avoiding concurrent use of opioids and benzodiazepines.
Learn More >Paediatric chronic pain is a significant problem that can have devastating impacts on quality of life. Multimodal interdisciplinary interventions are the mainstay of paediatric treatment. The aim of this article is to provide a comprehensive review of the effectiveness of interdisciplinary interventions in the management of paediatric chronic pain.
Learn More >Almotriptan, a serotonin 5-HT agonist has been used in the acute treatment of migraine with or without aura for 20 years, accumulating data on more than 15,000 patients in studies and from an estimated >150 million treated migraine attacks in daily clinical practice. The last major review of almotriptan was written almost 10 years ago. The current narrative review provides an overview of the experience gained with almotriptan over that time, and highlights data published in the last decade. Areas covered: Randomized clinical trials, observational studies, postmarketing studies and meta-analyses involving almotriptan for the treatment of acute migraine identified through a systematic literature search. Expert opinion: Triptans are a mainstay of anti-migraine treatment. Findings with ALT over the last 10 years have reinforced the positive efficacy and tolerability results that were reported during the first 10 years following its introduction. In particular, more recent clinical results have confirmed its efficacy in women with menstrual migraine, the usefulness of early intervention, long-term benefit in adults, and also its efficacy and safety in adolescents. Overall, ALT can be considered an optimal choice for managing acute migraine resistant to first-line drugs.
Learn More >Enhanced recovery pathways have quickly become part of the standard of care for patients undergoing elective surgery, especially in North America and Europe. One of the central tenets of this multidisciplinary approach is the use of multimodal analgesia with opioid-sparing and even opioid-free anesthesia and analgesia. However, the current state is a historically high use of opioids for both appropriate and inappropriate reasons, and patients with chronic opioid use before their surgery represent a common, often difficult-to-manage population for the enhanced recovery providers and health care team at large. Furthermore, limited evidence and few proven successful protocols exist to guide providers caring for these at-risk patients throughout their elective surgical experience. Therefore, the fourth Perioperative Quality Initiative brought together an international team of multidisciplinary experts, including anesthesiologists, nurse anesthetists, surgeons, pain specialists, neurologists, nurses, and other experts with the objective of providing consensus recommendations. Specifically, the goal of this consensus document is to minimize opioid-related complications by providing expert-based consensus recommendations that reflect the strength of the medical evidence regarding: (1) the definition, categorization, and risk stratification of patients receiving opioids before surgery; (2) optimal perioperative treatment strategies for patients receiving preoperative opioids; and (3) optimal discharge and continuity of care management practices for patients receiving opioids preoperatively. The overarching theme of this document is to provide health care providers with guidance to reduce potentially avoidable opioid-related complications including opioid dependence (both physical and behavioral), disability, and death. Enhanced recovery programs attempt to incorporate best practices into pathways of care. By presenting the available evidence for perioperative management of patients on opioids, this consensus panel hopes to encourage further development of pathways specific to this high-risk group to mitigate the often unintentional iatrogenic and untoward effects of opioids and to improve perioperative outcomes.
Learn More >Accurate tools for measuring physical activity are important for monitoring patients with chronic pain. However, these tools have not been properly validated in this population.
Learn More >The trigeminal root entry zone (TREZ) is the transitional zone of central and peripheral tissue compartments in the trigeminal root. Microvascular compression on the TREZ is the main etiology of most idiopathic trigeminal neuralgia (TN) patients. However, the pathogenesis of TN is still uncertain. To investigate the glial plasticity changes in oligodendrocytes, Schwann cells, astrocytes and microglia/macrophages in the TREZ in TN, immunohistochemical staining and Western blot methods were performed in rats with TN induced by compression injury. The results showed that mechanical compression injury in the trigeminal nerve of the TN rats induced glial plasticity in the TREZ, which dynamically changed the glial interface of the CNS-PNS transitional zone. Additionally, glial fibrillary acidic protein (GFAP)-immunoreactive astrocyte processes significantly proliferated and extended distally from the central region to the peripheral side of the TREZ after nerve compression injury in the TN group. Moreover, the expression of p75 in Schwann cells was upregulated on the peripheral side of the TREZ, and activated Iba-1-immunoreactive microglia/macrophages were observed on both sides of the TREZ. A significantly higher number of Schwann cells, astrocytes and microglia/macrophages were found in the TN group than in the sham operation group (p < 0.05). In conclusion, mechanical compression injury in the TN rats activated various glial cells, including oligodendrocytes, astrocytes, Schwann cells and microglia/macrophages, in the CNS-PNS transitional zone of TREZ. Changes in glial cell plasticity in the TREZ after compression injury might be involved in TN pathogenesis.
Learn More >Transmission of pain signals from primary sensory neurons to secondary neurons of the central nervous system is critically dependent on presynaptic voltage-gated calcium channels. Calcium channel-binding domain 3 (CBD3), derived from the collapsin response mediator protein 2 (CRMP2), is a peptide aptamer that is effective in blocking N-type voltage-gated calcium channel (Ca2.2) activity. We previously reported that recombinant adeno-associated virus (AAV)-mediated restricted expression of CBD3 affixed to enhanced green fluorescent protein (EGFP) in primary sensory neurons prevents the development of cutaneous mechanical hypersensitivity in a rat neuropathic pain model. In this study, we tested whether this strategy is effective in treating established pain. We constructed AAV6-EGFP-CBD3A6K (AAV6-CBD3A6K) expressing a fluorescent CBD3A6K (replacing A to K at position 6 of CBD3 peptide), which is an optimized variant of the parental CBD3 peptide that is a more potent blocker of Ca2.2. Delivery of AAV6-CBD3A6K into lumbar (L) 4 and 5 dorsal root ganglia (DRG) of rats 2 weeks following tibial nerve injury (TNI) induced transgene expression in neurons of these DRG and their axonal projections, accompanied by attenuation of pain behavior. We additionally observed that the increased Ca2.2α1b immunoreactivity in the ipsilateral spinal cord dorsal horn and DRG following TNI was significantly normalized by AAV6-CBD3A6K treatment. Finally, the increased neuronal activity in the ipsilateral dorsal horn that developed after TNI was reduced by AAV6-CBD3A6K treatment. Collectively, these results indicate that DRG-restricted AAV6 delivery of CBD3A6K is an effective analgesic molecular strategy for the treatment of established neuropathic pain.
Learn More >The monosodium iodoacetate (MIA)-induced joint degeneration in rats is the most used animal model to screen analgesic drugs to alleviate osteoarthritis (OA) pain. This study aimed to evaluate the analgesic efficacy of pregabalin (PGB) in an MIA-induced OA model in rodents by using functional and neuroproteomic pain assessment methods. Treatment group included PGB in curative intent over 9 days compared to gold standard therapy (positive controls) and placebo (negative control). Functional assessments of pain (quantitative sensory testing and operant test) were performed concomitantly with spinal neuropeptides quantification. At day 21 post-OA induction, PGB in MIA rats reduced tactile allodynia (P = 0.028) and improved the place escape/avoidance behavior (P = 0.04) compared to values recorded at last time-point before initiating analgesic therapy. All spinal neuropeptide concentrations, such as substance P, calcitonin gene-related peptide, bradykinin and somatostatin, came back to normal (non affected) rat values, compared to their increase observed in MIA rats receiving the placebo (P < 0.0001). Initiated 13 days after chemical OA induction, repeated medication with PGB provided analgesia according to quantitative sensory testing, operant test and targeted neuropeptides pain assessment methods. This report highlights the interest of using reliable and sensitive methods like targeted neuropeptide quantification to detect the analgesic effects of a test article with concomitant functional assessments of pain when studying OA pain components. This article is protected by copyright. All rights reserved.
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