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Evaluate the effect of upadacitinib on pain outcomes in patients with active psoriatic arthritis (PsA) or ankylosing spondylitis (AS) across 3 randomised trials (SELECT-PsA 1 and 2 for PsA; SELECT-AXIS 1 for AS).
Learn More >One of the factors contributing to transformation of migraine are sleep disorders, which can act as a trigger and/or perpetuating factor in these patients. This study's primary objective was to identify predictive factors related to sleep quality in patients with chronic migraine (CM); the secondary objective was to identify any differences in psychological variables and disability between patients with CM with better or poorer sleep quality.
Learn More >Understanding how pharmaceutical opioids and antipyretic analgesics interact with the immune system potentially has major clinical implications for management of patients with infectious diseases and surgical and critical care patients. An electronic search was carried out on MEDLINE, EMBASE, PsycINFO, CENTRAL and the Cochrane library to identify reports describing the immunomodulatory effects of opioid analgesics and antipyretic analgesics, and their effects in infectious diseases. In adaptive immunity, nonsteroidal anti-inflammatory drugs have divergent effects: augmenting cell-mediated immunity but inhibiting humoral immunity. Nonsteroidal anti-inflammatory drugs have demonstrated a beneficial role in Mycobacterium tuberculosis infection and histoplasmosis in animals, and may be plausible adjuvants to antimicrobial agents in these diseases. There is a need to evaluate these findings rigorously in human clinical trials. There is preliminary evidence demonstrating antiviral effects of indomethacin in SARS CoV-2 in vitro; however, uncertainty regarding its clinical benefit in humans needs to be resolved in large clinical trials. Certain opioid analgesics are associated with immunosuppressive effects, with a developing understanding that fentanyl, morphine, methadone and buprenorphine suppress innate immunity, whilst having diverse effects on adaptive immunity. Morphine suppresses key cells of the innate immunity and is associated with greater risk of infection in the postsurgical setting. Efforts are needed to achieve adequate analgesia whilst avoiding suppression of the innate immunity in the immediate postoperative period caused by certain opioids, particularly in cancer surgery.
Learn More >Transient receptor potential melastatin subtype 8 (TRPM8) is a cation channel extensively expressed in sensory neurons and implicated in different painful states. However, the effectiveness of TRPM8 modulators for pain relief is still a matter of discussion, since structurally diverse modulators lead to different results, depending on the animal pain model. In this work, we described the antinociceptive activity of a β-lactam derivative, RGM8-51, showing good TRPM8 antagonist activity, and selectivity against related thermoTRP channels and other pain-mediating receptors. In primary cultures of rat dorsal root ganglion (DRG) neurons, RGM8-51 potently reduced menthol-evoked neuronal firing without affecting the major ion conductances responsible for action potential generation. This compound has in vivo antinociceptive activity in response to cold, in a mouse model of oxaliplatin-induced peripheral neuropathy. In addition, it reduces cold, mechanical and heat hypersensitivity in a rat model of neuropathic pain arising after chronic constriction of the sciatic nerve. Furthermore, RGM8-51 exhibits mechanical hypersensitivity-relieving activity, in a mouse model of NTG-induced hyperesthesia. Taken together, these preclinical results substantiate that this TRPM8 antagonist is a promising pharmacological tool to study TRPM8-related diseases.
Learn More >The common technique using a basal infusion for an ambulatory continuous peripheral nerve blocks frequently results in exhaustion of the local anesthetic reservoir prior to resolution of surgical pain. We sought to improve and prolong analgesia by delaying initiation using an integrated timer and delivering a lower hourly volume of local anesthetic as automated boluses. We hypothesized that, compared with a traditional continuous infusion, ropivacaine administered with automated boluses at a lower dose and 5-hour delay would (1) provide at least noninferior analgesia [difference in average pain no greater than 1.7 points] while both techniques were functioning [average pain score day after surgery]; and, (2) result in a longer duration [dual primary outcomes].
Learn More >Neuropathic pain indicates pain caused by damage to the somatosensory system and is difficult to manage and treat. A new treatment strategy urgently needs to be developed. Both autophagy and apoptosis are critical adaptive mechanisms when neurons encounter stress or damage. Recent studies have shown that, after nerve damage, both autophagic and apoptotic activities in the injured nerve, dorsal root ganglia, and spinal dorsal horn change over time. Many studies have shown that upregulated autophagic activities may help myelin clearance, promote nerve regeneration, and attenuate pain behavior. On the other hand, there is no direct evidence that the inhibition of apoptotic activities in the injured neurons can attenuate pain behavior. Most studies have only shown that agents can simultaneously attenuate pain behavior and inhibit apoptotic activities in the injured dorsal root ganglia. Autophagy and apoptosis can crosstalk with each other through various proteins and proinflammatory cytokine expressions. Proinflammatory cytokines can promote both autophagic/apoptotic activities and neuropathic pain formation, whereas autophagy can inhibit proinflammatory cytokine activities and further attenuate pain behaviors. Thus, agents that can enhance autophagic activities but suppress apoptotic activities on the injured nerve and dorsal root ganglia can treat neuropathic pain. Here, we summarized the evolving changes in apoptotic and autophagic activities in the injured nerve, dorsal root ganglia, spinal cord, and brain after nerve damage. This review may help in further understanding the treatment strategy for neuropathic pain during nerve injury by modulating apoptotic/autophagic activities and proinflammatory cytokines in the nervous system.
Learn More >Excessive intravascular release of lysed cellular contents from damaged red blood cells (RBCs) in patients with sickle cell anemia (SCA) can activate the inflammasome, a multiprotein oligomer promoting maturation and secretion of pro-inflammatory cytokines, including interleukin 1-beta (IL-1b). We hypothesized that IL-1b blockade by canakinumab in patients with SCA would reduce markers of inflammation and clinical disease activity. In this randomized, double-blind, multi-center phase 2a study, patients aged 8-20 years old with SCA (HbSS or HbSb0thalassemia), history of acute pain episodes and elevated hsCRP >1.0 mg/L at screening were randomized 1:1 to received 6 monthly treatments with 300 mg s.c. canakinumab or placebo. Measured outcomes at baseline and weeks 4, 8, 12, 16, 20 and 24 included electronic patient-reported outcomes, hospitalization rate and adverse events (AEs) and serious AEs (SAEs). All but one of the 49 enrolled patients were receiving stable background hydroxyurea therapy. Although the primary objective (pre-specified reduction of pain) was not met, compared to placebo-arm patients, canakinumab-treated patients had reductions in markers of inflammation, occurrence of SCA-related AE and SAE, and number and duration of hospitalizations, as well as trends for improvement in pain intensity, fatigue and absences from school or work. Post-hoc analysis revealed treatment effects on weight, restricted to pediatric patients. Canakinumab was well tolerated with no treatment-related SAEs and no new safety signal. These findings demonstrate that the inflammation associated with SCA can be reduced by selective IL-1b blockade by canakinumab with potential for therapeutic benefits. This trial was registered at www.clinicaltrials.gov as NCT02961218.
Learn More >Atopic dermatitis (AD) is a chronic, inflammatory skin disease with persistent and severe itch among its hallmark features. Significant increases in type 2 cytokines (i.e., IL-4, IL-13, IL-31) have been documented in acute AD lesions and lead to multi-faceted downstream effects, including inflammation, epidermal barrier dysfunction, and itch.
Learn More >Headache, both before and after injury, has been associated with worse outcome following mild traumatic brain injury (MTBI). This study examined whether three MTBI patient groups – no headache (reported no pre-/post-injury headache), pre-injury headache (reported pre-injury headache, nearly all of whom also reported post-injury headache), and post-traumatic headache only (denied pre-injury headache and reported post-injury headache) – differed in acute-to-subacute outcomes.
Learn More >The experience of chronic pain is influenced by gender, race, and age but is understudied in older Black women. Society and family alike expect Black older women to display superhuman strength and unwavering resilience. This qualitative study examined the narratives of 9 rural- and urban-dwelling Black older women to identify the ways in which they displayed strength while living with chronic osteoarthritis pain. Their "herstories" parallel the 5 characteristics of the Superwoman Schema/Strong Black Woman. Two additional characterizations emerged: spiritual submission for strength and code switching to suffering Black woman; these may be unique to Black Americans with pain.
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