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The objective was to investigate the efficacy and safety of soticlestat as adjunctive therapy in participants with complex regional pain syndrome (CRPS).

The thalamocortical (TC) circuit is closely associated with pain processing. The hyperpolarization-activated cyclic nucleotide-gated (HCN) 2 channel is predominantly expressed in the ventral posterolateral thalamus (VPL) that has been shown to mediate neuropathic pain. However, the role of VPL HCN2 in modulating TC circuit activity is largely unknown. Here, by using optogenetics, neuronal tracing, electrophysiological recordings, and virus knockdown strategies, we showed that the activation of VPL TC neurons potentiates excitatory synaptic transmission to the hindlimb region of the primary somatosensory cortex (S1HL) as well as mechanical hypersensitivity following spared nerve injury (SNI)-induced neuropathic pain in mice. Either pharmacological blockade or virus knockdown of HCN2 (shRNA-Hcn2) in the VPL was sufficient to alleviate SNI-induced hyperalgesia. Moreover, shRNA-Hcn2 decreased the excitability of TC neurons and synaptic transmission of the VPL-S1HL circuit. Together, our studies provide a novel mechanism by which HCN2 enhances the excitability of the TC circuit to facilitate neuropathic pain.

Ruxolitinib cream 1.5% (OPZELURA™) is a topical formulation of ruxolitinib, a potent, selective inhibitor of Janus kinase (JAK)1 and JAK2. The targeting of these kinases is associated with therapeutic benefits in patients with atopic dermatitis (AD). In two identically designed, multinational, phase III studies in patients aged ≥ 12 years with mild to moderate AD, ruxolitinib cream 1.5% improved measures of disease severity, pruritus and sleep disturbance relative to vehicle cream when applied twice daily for 8 weeks. Disease severity was controlled for the next 44 weeks when applied as needed to active lesions. Ruxolitinib cream 1.5% was well tolerated in this patient population; its safety profile was similar to that of vehicle cream over the short term, with the types of treatment-emergent adverse events typical of those seen in the vehicle-controlled period over the longer term. Moreover, application site treatment-emergent adverse events indicative of skin tolerability issues (e.g. stinging/burning sensation) were infrequent and no safety findings suggestive of systemic JAK inhibition were identified. Although further longer-term data would be of use, ruxolitinib cream 1.5% provides an alternative to established topical agents (e.g. corticosteroids and calcineurin inhibitors) for the treatment of mild to moderate AD in adults and adolescents.

Diagnosis of hip osteoarthritis (OA) is based on clinical arguments, and medical imaging is obtained to confirm the diagnosis and rule out other possible sources of pain. Conventional radiographs are recommended as the first line imaging modality to investigate chronic hip pain. They should be obtained in a rigorous technique that includes an antero-posterior (AP) radiograph of the pelvis. The choice of the appropriate lateral view depends on the clinical indication, Lequesne's false profile being valuable in the assessment of OA. Magnetic resonance imaging (MRI) is more sensitive to detect joint effusion/synovitis, cartilage, labral, and bone marrow lesions. However, structural joint changes are frequent in asymptomatic population and neither radiographs nor MRI have shown a good correlation with pain and functional impairment. MRI seems to be more suitable than radiographs as a biomarker for clinical trials addressing early OA. The absence of a validated MR biomarker of early OA, together with issues related to machine availability and MRI protocol repeatability, prevent the widespread use of MRI in clinical trials.

Animal models have consistently indicated that central sensitization and the development of chronic neuropathic pain is linked to changes to inhibitory signalling in the dorsal horn of the spinal cord. However, replication of data investigating the cellular mechanisms that underly these changes remain a challenge and there is still a lack of understanding about what aspects of spinal inhibitory transmission most strongly contribute to the disease. Here, we compared the effect of two different sciatic nerve injuries commonly used to generate rodent models of neuropathic pain on spinal glycinergic signalling. Using whole-cell patch-clamp electrophysiology in spinal slices, we recorded from neurons in the lamina II of the dorsal horn and evoked inhibitory postsynaptic currents with a stimulator in lamina III, where glycinergic cell bodies are concentrated. We found that glycine inputs onto radial neurons were reduced following partial nerve ligation (PNL) of the sciatic nerve, consistent with a previous report. However, this finding was not replicated in animals that underwent chronic constriction injury (CCI) to the same nerve region. To limit the between-experiment variability, we kept the rat species, sex, and age consistent and had a single investigator carry out the surgeries. These data show that PNL and CCI cause divergent spinal signalling outcomes in the cord and add to the body of evidence suggesting that treatments for neuropathic pain should be triaged according to nerve injury or cellular dysfunction rather than the symptoms of the disease.

An expanding array of image-guided spine interventions have the potential to provide immediate and effective pain relief. Innovations in spine intervention have proceeded rapidly, with clinical adoption of new techniques at times occurring before the development of bodies of evidence to establish efficacy. Although new spine interventions have been evaluated by clinical trials, acceptance of results has been hindered by controversies regarding trial methodology. This article explores controversial aspects of four categories of image-guided interventions for painful conditions: spine interventions for postdural puncture headache resulting from prior lumbar procedures; epidural steroid injections for cervical and lumbar radiculopathy; facet and sacroiliac joint pain interventions; and vertebral augmentations for compression fractures. For each intervention, we summarize the available literature with an emphasis on persistent controversies and discuss how current areas of disagreement and challenge may shape future research and innovation. Despite the ongoing areas of debate for various aspects of these procedures, effective treatments continue to emerge and show promise for aiding relief on a range of debilitating conditions.

Fatigue is a symptom that can negatively impact patients' quality of life. However, the relationship of AD with fatigue has not been fully studied, especially in children.

Self-efficacy is one of the important factors affecting chronic diseases. In the current epidemiological context of low back pain (LBP), LBP self-efficacy has become a topic of great practical interest for researchers. However, no bibliometric analysis related to LBP self-efficacy has been performed to date. The purpose of this study was to conduct and explore the current state of research in LBP self-efficacy from 1980 to 2021, by using bibliometric analysis and scientific mapping.

Itching and skin pain are bothersome symptoms of psoriasis, but evidence is limited regarding the treatment effectiveness on these symptoms in daily clinical settings. We assessed the changes in the levels of itching and skin pain after brodalumab treatment in Japanese patients with psoriasis using patient-reported outcomes (PROs). Patients with psoriasis who have inadequate response to existing treatments were enrolled in the single-arm, open-label, multicenter, prospective ProLOGUE study and received brodalumab 210 mg subcutaneously in daily clinical practice. Psoriasis Area and Severity Index (PASI) and PRO assessments were performed at baseline and weeks 12 and 48. Seventy-three patients (men, 82.2%; median age, 54.0 years) were enrolled. The Itch Numeric Rating Scale (NRS; p < 0.0001 at weeks 12 and 48) and Skin Pain NRS (week 12, p = 0.0004; week 48, p < 0.0001) scores significantly decreased from baseline. The Itch NRS score was significantly higher in patients with a Dermatology Life Quality Index (DLQI) score of ≥2 (vs. 0/1; p < 0.0001 at weeks 12 and 48) and in patients with a Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) global satisfaction domain score of ≤70% (vs. >70%; week 12, p = 0.0120; week 48, p = 0.0348). The Itch NRS score cutoff value for achieving a PASI score of ≤2, DLQI score of 0/1, and TSQM-9 global satisfaction domain score of >70% was 1 at week 12 and 0 at week 48. Brodalumab treatment was associated with improvement in itching and skin pain in Japanese patients with psoriasis. An Itch NRS score of 0 can be a long-term treatment goal for psoriasis (Japan Registry of Clinical Trials identifier: jRCTs031180037).