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The pathophysiology of cluster headache and how cluster episodes are triggered, are still poorly understood. Recurrent inflammation of the trigeminovascular system has been hypothesized. It was noted that some long-term attack-free cluster headache patients suddenly developed a new cluster episode shortly after COVID-19 vaccination.
Learn More >The modern management of chronic pain is largely focused on improving functional capacity (often despite ongoing pain) by using graded activation and exposure paradigms. However, many people with chronic pain find functional activation programs aversive, and dropout rates are high. Modern technologies such as virtual reality (VR) could provide a more enjoyable and less threatening way for people with chronic pain to engage in physical activity. Although VR has been successfully used for pain relief in acute and chronic pain settings, as well as to facilitate rehabilitation in conditions such as stroke and cerebral palsy, it is not known whether VR can also be used to improve functional outcomes in people with chronic pain.
Learn More >Although sleep quantity and quality appear to be interrelated, most previous studies have considered sleep duration and insomnia symptoms as distinct entities. We therefore examined whether there is a joint effect of sleep duration and long-term changes in insomnia symptoms on the risk of recurrent chronic spinal pain. We performed a prospective study of 8,788 participants who participated in three surveys over ∼22 years and reported chronic spinal pain at the first, second, or both surveys. Adjusted risk ratios (RRs) were calculated for the risk of recurrent spinal pain at the last survey associated with self-reported sleep duration at the first survey and changes in insomnia symptoms between the two first surveys. Compared to participants with normal sleep duration (7-9 h) and no insomnia symptoms at the two first surveys, participants with insomnia symptoms over the same period had RRs of spinal pain of 1.33 (95% CI 1.26-1.41) in the last survey if they reported normal sleep duration and 1.50 (95% CI 1.34-1.67) if they reported short sleep (≤6 h). The corresponding RRs for spinal pain for participants who improved their sleep symptoms were 1.09 (95% CI 1.00-1.19) for those with normal sleep and 1.13 (95% CI 0.88-1.45) for those with short sleep. In conclusion, people who reported insomnia symptoms over ∼10 years in combination with short sleep had a particularly increased risk of recurrent spinal pain. Improvement in insomnia symptoms was associated with a favorable prognosis.
Learn More >Fibromyalgia is a prevalent disorder manifesting with widespread musculoskeletal pain and central sensitization, as well as fatigue, sleep issues, psychologic distress, and poor quality of life. Patients with fibromyalgia also may be diagnosed with other painful conditions amenable to treatment with spinal cord stimulation (SCS), although it is unclear how these patients respond to SCS compared with patients without fibromyalgia.
Learn More >Pain is a warning signal for the body defense mechanisms and is a critical sensation for supporting life. However, orofacial pain is not a vital sensation, but a disease. However, there are still many unclear points about the pathophysiological mechanism of orofacial pain. This situation makes it difficult for many clinicians to treat orofacial pain hypersensitivity.
Learn More >Several functional neuroimaging studies on healthy controls and patients with migraine with aura have shown that the activation of functional networks during visual stimulation is not restricted to the striate system, but also includes several extrastriate networks.
Learn More >Although nonsteroidal anti-inflammatory drugs (NSAIDs) are medicines that are widely used to relieve pain, reduce inflammation, and bring down high temperature, literature confirmed that they still have harmful side effects. Most of their side effects are in the digestive system due to the carboxylic group. As naproxen is one of the NSAIDs, in this work, we try to mask the carboxylic group in naproxen with a relatively safe functional group. So, herein, we report the synthesis of new naproxen-based hydrazones derivatives, namely, (E)-N'-1-(4-chlorophenyl)ethylidene)-2-(6-methoxynaphthalen-2-yl)propane hydrazide (4a) and (E)-N'-(4-hydroxybenzylidene)-2-(6-methoxynaphthalen-2-yl)propane hydrazide ethanol solvate (4b). The compounds were confirmed by X-ray diffraction studies. Hirshfeld surface analyses and energy frameworks of 4a and 4b have been carried out and blind molecular docking studies of them to the COX-2 enzyme were undertaken to obtain binding affinities for judging whether the compounds could act as anti-inflammatory agents. The compounds interact with the key residues: Arg120, Val349, Leu352, Tyr355, Val523, Ala527, Ser530, and Leu531 of the active enzyme pocket. Molecular dynamics studies predicted that the complexes of 4a and 4b with COX-2 are structurally stable and no major conformational changes were observed. Confirmation of the docking and simulation data was achieved by a binding free energies analysis that indicated the dominance of van der Waals energy. The compounds are drug-like molecules as they obey all prominent drug-like rules and have acceptable pharmacokinetic profiles. To investigate the relationship between their intrinsic electronic properties and their possible similarities to actual drugs, the gas-phase DFT optimizations and NBO analyses were also performed in this study.
Learn More >Rheumatoid arthritis (RA) is an inflammatory type of arthritis that causes joint pain and damage. The inflammatory cell infiltration (e.g., M1 macrophages), the poor O supply at the joint, and the excess reactive oxygen species (ROS)-induced oxidative injury are the main causes of RA. We herein report a polydopamine (PDA)-coated CeO-dopped zeolitic imidazolate framework-8 (ZIF-8) nanocomposite CeO-ZIF-8@PDA (denoted as ) that can synergistically treat RA. Under near-infrared (NIR) light irradiation, PDA efficiently scavenges ROS and results in an increased temperature in the inflamed area because of its good light-to-heat conversion efficiency. The rise of temperature serves to obliterate hyper-proliferative inflammatory cells accumulated in the diseased area while vastly promoting the collapse of the acidic-responsive skeleton of ZIF-8 to release the encapsulated CeO. The released CeO exerts its catalase-like activity to relieve hypoxia by generating oxygen via the decomposition of HO highly expressed in the inflammatory sites. Thus, the constructed composite can treat RA through NIR-photothermal/ROS-scavenging/oxygen-enriched combinative therapy and show good regression of pro-inflammatory cytokines and hypoxia-inducible factor-1α (HIF-1α) in vitro and promising therapeutic effect on RA in rat models. The multimodal nano-platform reported herein is expected to shed light on the design of synergistic therapeutic nanomedicine for effective RA therapy.
Learn More >Headache is one of the most frequently reported symptoms in post-COVID patients. The clinical phenotype of COVID-19 headache combines phenotypic features of both tension-type headache (TTH) and migraine. We aimed to assess the effectiveness, side effects and predictors of amitriptyline (AMT) response in a real-world study setting.
Learn More >Post-amputation pain causes great suffering to amputees, but still no effective drugs are available due to its elusive mechanisms. Our previous clinical studies found that surgical removal or radiofrequency treatment of the neuroma at the axotomized nerve stump effectively relieves the phantom pain afflicting patients after amputation. This indicated an essential role of the residual nerve stump in the formation of chronic post-amputation pain (CPAP). However, the molecular mechanism by which the residual nerve stump or neuroma is involved and regulates CPAP is still a mystery. In this study, we found that nociceptors expressed the mechanosensitive ion channel TMEM63A and macrophages infiltrated into the dorsal root ganglion (DRG) neurons worked synergistically to promote CPAP. Histology and qRT-PCR showed that TMEM63A was mainly expressed in mechanical pain-producing non-peptidergic nociceptors in the DRG, and the expression of TMEM63A increased significantly both in the neuroma from amputated patients and the DRG in a mouse model of tibial nerve transfer (TNT). Behavioral tests showed that the mechanical, heat, and cold sensitivity were not affected in the Tmem63a mice in the naïve state, suggesting the basal pain was not affected. In the inflammatory and post-amputation state, the mechanical allodynia but not the heat hyperalgesia or cold allodynia was significantly decreased in Tmem63a mice. Further study showed that there was severe neuronal injury and macrophage infiltration in the DRG, tibial nerve, residual stump, and the neuroma-like structure of the TNT mouse model, Consistent with this, expression of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β all increased dramatically in the DRG. Interestingly, the deletion of Tmem63a significantly reduced the macrophage infiltration in the DRG but not in the tibial nerve stump. Furthermore, the ablation of macrophages significantly reduced both the expression of Tmem63a and the mechanical allodynia in the TNT mouse model, indicating an interaction between nociceptors and macrophages, and that these two factors gang up together to regulate the formation of CPAP. This provides a new insight into the mechanisms underlying CPAP and potential drug targets its treatment.
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