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Restorative neurostimulation is a rehabilitative treatment for patients with refractory chronic low back pain (CLBP) associated with dysfunction of the lumbar multifidus muscle resulting in impaired neuromuscular control. The ReActiv8-B randomized, sham-controlled trial provided evidence of the effectiveness and safety of an implanted, restorative neurostimulator. The two-year analysis previously published in this journal demonstrated accrual of clinical benefits and long-term durability.
Learn More >There is increasing evidence that some biomarkers are implicated in migraine pathogenesis. This study looks at plasma proteome in migraine patients for potential protein biomarkers.
Learn More >Pain is a personalized event or body alarm system that can limit a patient's activities and lead to negative repercussions. The commercially available conventional treatment strategies like oral, parenteral, and topical drug delivery systems for pain management are associated with side effects and poor patient compliance. The transdermal route is eminent for its painless distribution. Among transdermal drug delivery system, microneedles (MNs) are gaining attention for their application with delivery at the deeper dermal layer because it bypasses the major barrier of the skin, easily accesses the skin dermal microcirculation, prevents damage to dermal blood vessels, and can be simply inserted into the skin without utilizing any additional applicator devices. Hence, considered a promising drug delivery strategy with high patient compliance. This review highlights the recent advancements of MNs in pain management. The present work mainly emphasizes all the case studies reported from the past 10 years that utilize MNs containing therapeutics in the treatment of chronic pain-associated diseases like rheumatoid arthritis, neuropathic pain, osteoarthritis, psoriatic arthritis, and atopic dermatitis. These studies have proven the efficacious application of MNs in the management of chronic pain and inflammation. The review also covered the clinical trials, patents, and future goals of pain management by using MNs.
Learn More >T-type Ca2+ channels play a dual role in modulating the excitability of dorsal root ganglia neurons.
A subgroup of low-threshold dorsal root ganglia (DRG) neurons discharge action potentials (APs) with an afterdepolarizing potential (ADP). The ADP is formed by T-type Ca2+ currents. It is known that T-type Ca2+ currents contribute to neuropathic pain. However, the change in ADP-firing of injured DRG neurons has not been widely studied yet. Here we applied patch clamp to record ADP-firing and T-type Ca2+ currents in intact and chronically compressed DRG (CCD) neurons and examined T-type Ca2+ channel proteins expression with western blotting. After CCD injury, the incidences of both ADP firing and non-ADP burst firing increased, and T-type Ca2+ channels contributed to both of these firing patterns. The neurons discharging large-amplitude-ADP firing were TTX-insensitive, implying that high-density T-type Ca2+ channels might cooperate with TTX-insensitive Na+ channels to reduce the AP threshold. By contrast, the neurons displaying non-ADP burst firing were TTX-sensitive, implying that low density T-type Ca2+ channels may cooperate with TTX-sensitive Na+ channels to increase AP number. In DRG neurons, T-type Ca2+ currents density varied widely, ranging between 100 pA/pF and 5 pA/pF. After injury, the proportion of DRG neurons with large T-type Ca2+ currents increased in parallel with the increase in the incidence of large-amplitude-ADP firing. And in addition to Cav3.2, Cav3.3 channels are also likely to contribute to low-threshold firing. The data revealed that T-type Ca2+ channels may play a dual role in modulating the injured neurons' high excitability through a cooperative process with Na+ channels, thereby contributing to neuropathic pain.
Learn More >Pain usually receives insufficient attention by individuals due to the misconception that pain is a natural consequence of aging. For persons aged 65 and older, a disease requiring further research is fibromyalgia, characterized by chronic pain without clear pathology. Mind-body therapies like mindfulness are beneficial for this population as they affect psychological and biological aspects of pain. These therapies emphasize a nonjudgmental acceptance of thoughts and attention to the experience without attempting to resist or change them. Despite the potential benefits of mindfulness interventions for persons with fibromyalgia aged 65 and older, only few studies have examined the effects of these therapies, yielding conflicting findings. Importantly, no study has yet to be conducted exclusively on this population. This comprehensive review examined existing literature focusing on the effects of mindfulness-based interventions on the physical and mental well-being of persons with fibromyalgia aged 65 and older. It highlights the need for further research on the relationship between mindfulness, fibromyalgia, and gerontology, calling for a standard protocol of intervention.
Learn More >Our aim was to assess the association between four inflammatory polymorphisms with the development of post-COVID pain and to associate these polymorphisms with the clinical pain phenotype in individuals who had been hospitalized by COVID-19. Three potential genotypes of IL-6 (rs1800796), IL-10 (rs1800896), TNF-α (rs1800629), and IFITM3 (rs12252) single nucleotide polymorphisms (SNPs) were obtained from no-stimulated saliva samples from 293 (49.5% female, mean age: 55.6 ± 12.9 years) previously hospitalized COVID-19 survivors by polymerase chain reactions. Pain phenotyping consisted of the evaluation of pain features, sensitization-associated symptoms, anxiety levels, depressive levels, sleep quality, catastrophizing, and kinesiophobia levels in patients with post-COVID pain. Analyses were conducted to associate clinical features with genotypes. One hundred and seventeen (39.9%) patients experienced post-COVID pain 17.8 ± 5.2 months after hospital discharge. No significant differences in the distribution of the genotype variants of any SNPs were identified between COVID-19 survivors with and without post-COVID pain (all, > 0.47). Similarly, the clinical pain phenotype was not significantly different between patients with and without post-COVID pain since no differences in any variable were observed for any SNPs. In conclusion, four SNPs associated with inflammatory and immune responses did not appear to be associated with post-COVID pain in previously hospitalized COVID-19 survivors. Further, neither of the SNPs were involved in the phenotyping features of post-COVID pain.
Learn More >Neuropathic pain is well known to occur after damage to the somatosensory system. Aryl hydrocarbon receptor (AhR) has neuroprotective effects when the central nervous system is subjected to internal and external stimulations. However, the exact mechanism by which AhR regulates neuropathic pain is poorly understood. Nerve explant culture and the chronic constrictive nerve injury (CCI) model in wild or AhR-knockout mice were used in this study. In the nerve explant culture, the ovoid number increased in the AhR-/- condition and was decreased by omeprazole (AhR agonist) in a dose-dependent manner. Increased nerve degeneration and the associated inflammation response appeared in the AhR-/- condition, and these changes were attenuated by omeprazole. High expression of AhR in the injured nerve was noted after CCI. Deletion of AhR aggravated nerve damages and this was restored by omeprazole. Deletion of AhR increased NGF expression and reduced axon number in the paw skin, but this was attenuated by omeprazole. A highly expressed inflammation reaction over the dorsal spinal cord, somatosensory cortex, and hippocampus was noted in the AhR-deleted animals. Administration of omeprazole attenuated not only the inflammatory response, but also the amplitude of somatosensory evoked potential. Deletion of AhR further aggravated the neurobehavior compared with the wild type, but such behavior was attenuated by omeprazole. Chronic constrictive nerve injury augmented AhR expression of the injured nerve, and AhR deletion worsened the damage, while AhR agonist omeprazole counteracted such changes. AhR agonists could be potential candidates for neuropathic pain treatment.
Learn More >Fibromyalgia (FM) is a disease characterized by widespread musculoskeletal chronic pain that impairs the patient's quality of life and is considered a somatization disorder. The symptoms of the disease also affect the patient mentally, mainly since invisible pain is the only thing that indicates its existence. A typical symptom that characterizes FM patients is the lack of acceptance of the disease since its pathophysiology is not elucidated, hence the deficiencies in its management, or rather, cognitively, the belief that there is no disease to manage. The current paper aims to shed light on the new treatment methods at a holistic level, that is, cognitive, physical, and pharmacological therapies.
Learn More >Ehlers-Danlos syndrome (EDS) represents a family of heritable connective tissue disorders with overlapping phenotypic features, frequently including joint hypermobility, tissue fragility, and skin hyperextensibility. Comorbid symptoms are common for patients with EDS and include multiple body systems marked by neurologic, cardiovascular, gastrointestinal, musculoskeletal issues, chronic pain, headaches, and anxiety and depression. The many comorbidities lead to high disease burden, which requires greater healthcare utilization.
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