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Functional connectivity impairment of thalamus-cerebellum-scratching neural circuits in pruritus of chronic spontaneous urticaria.

Pruritus of chronic spontaneous urticaria (CSU) is one of the most common and irritating sensations that severely affects the quality of life. However, the changes in the functional connectivity (FC) between thalamic subregions and other brain regions have not been fully elucidated. This study aimed to explore the potential changes in brain neural circuits by focusing on various subregions of the thalamus in patients with CSU pruritus to contribute to the understanding of chronic pruritus from the perspective of central mechanisms. A total of 56 patients with CSU and 30 healthy controls (HCs) completed the data analysis. Urticaria Activity Score 7 (UAS7), pruritus visual analog score (VAS-P), Dermatological Life Quality Index (DLQI), and immunoglobulin E (IgE) values were collected to assess clinical symptoms. Seed-based resting-state functional connectivity (rs-FC) analysis was used to assess relevant changes in the neural circuits of the brain. Compared to HCs, seeds within the caudal temporal thalamus (cTtha) on the right side of patients with CSU showed increased rs-FC with the cerebellum anterior lobe (CAL). Seeds within the lateral prefrontal thalamus (lPFtha) on the right side showed increased rs-FC with both CAL and pons, while those within the medial prefrontal thalamus (mPFtha) on the right side showed increased rs-FC with both CAL and the dorsal lateral prefrontal cortex (dlPFC) on the right side. Seeds within the posterior parietal thalamus (PPtha) on the right side showed increased rs-FC with the cerebellum posterior lobe (CPL) on the left side. The UAS7 values and IgE levels were positively correlated with the rs-FC of the right dlPFC. Our results suggest that patients with CSU may exhibit stronger rs-FC alterations between certain thalamic subregions and other brain regions. These changes affect areas of the brain involved in sensorimotor and scratching.

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Topology of pain networks in patients with temporomandibular disorder and pain-free controls with and without concurrent experimental pain: A pilot study.

Temporomandibular disorders (TMD) involve chronic pain in the masticatory muscles and jaw joints, but the mechanisms underlying the pain are heterogenous and vary across individuals. In some cases, structural, functional, and metabolic changes in the brain may underlie the condition. In the present study, we evaluated the functional connectivity between 86 regions of interest (ROIs), which were chosen based on previously reported neuroimaging studies of pain and differences in brain morphology identified in an initial surface-based morphometry analysis. Our main objectives were to investigate the topology of the network formed by these ROIs and how it differs between individuals with TMD and chronic pain ( = 16) and pain-free control participants ( = 12). In addition to a true resting state functional connectivity scan, we also measured functional connectivity during a 6-min application of a noxious cuff stimulus applied to the left leg. Our principal finding is individuals with TMD exhibit more suprathreshold correlations (higher nodal degree) among all ROIs but fewer "hub" nodes (i.e., decreased betweenness centrality) across conditions and across all pain pathways. These results suggest is this pain-related network of nodes may be "over-wired" in individuals with TMD and chronic pain compared to controls, both at rest and during experimental pain.

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Mechanisms of exercise for diabetic neuropathic pain.

Diabetic neuropathic pain (DNP) is a common disease that affects the daily lives of diabetic patients, and its incidence rate is very high worldwide. At present, drug and exercise therapies are common treatments for DNP. Drug therapy has various side effects. In recent years, exercise therapy has received frequent research and increasing attention by many researchers. Currently, the treatment of DNP is generally symptomatic. We can better select the appropriate exercise prescription for DNP only by clarifying the exercise mechanism for its therapy. The unique pathological mechanism of DNP is still unclear and may be related to the pathological mechanism of diabetic neuropathy. In this study, the mechanisms of exercise therapy for DNP were reviewed to understand better the role of exercise therapy in treating DNP.

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Therapeutic Potential of Diacerein in Management of Pain.

Diacerein (DCN), an analogue of rhein (a glycosidal compound of natural origin), is currently used in the treatment of osteoarthritis and is given a fast-track designation for development to treat epidermolysis bullosa (EB). It is a nonsteroidal anti-inflammatory drug having disease-modifying properties in osteoarthritis and anti-inflammatory effects for the treatment of EB. Diacerein has a beneficial effect on pain relief and demonstrated antioxidant and anti-apoptotic effects, which are useful in renal disease, diabetes, and other disorders. This review discusses the possible mechanism of diacerein in the management of pain. The potential role of rhein and diacerein in the treatment of neuropathic, inflammatory and nociceptive pain is also reviewed. The effect of diacerein and rhein on mediators of pain, such as transient receptor potential cation channel subfamily V (TRPV1), Substance P, glutamate, inflammatory cytokines, nitric oxide, matrix metalloproteinases, histamine, palmitoylethanolamide, nuclear factor-kappa B (NFkB), and prostaglandin, has also been discussed. The data highlights the role of diacerein in neuropathic, nociceptive and inflammatory pain. Clinical trials and mechanism of action studies are needed to ascertain the role of diacerein, rhein or their analogues in the management of pain, alone or in combination with other approved therapies.

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Relationship between Postoperative Pain and Sociocultural Level in Major Orthopedic Surgery.

Total knee arthroplasty (TKA) and total hip arthroplasty (THA) are associated with moderate to severe postoperative pain (POP). POP is theoretically predictable and may be influenced by sociocultural differences. This study aimed to identify the relationship between POP and the sociocultural level of the patient undergoing THA or TKA.

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Proteomic and metabolomic profiling of acupuncture for migraine reveals a correlative link via energy metabolism.

Migraine is a neurovascular disease with a high disability rate. Acupuncture treatment has emerged as a safe and viable alternative prophylactic therapy that can effectively alleviate the duration and frequency of migraine attacks. However, the therapeutic mechanisms underlying the effects of acupuncture are yet to be systematically elucidated. In this study, we enrolled female patients with migraine without aura ( = 20) and healthy controls ( = 10). Patients received acupuncture treatment on DU20, DU24, bilateral GB13, GB8, and GB20, applied three times per week over the course of 4 weeks for 12 sessions in total. Blood samples were collected from the median cubital vein before and after acupuncture treatment. Proteomic and metabolomic profiling was performed using liquid chromatography-mass spectrometry to determine the characteristics of differentially expressed molecules and expression of their corresponding biological pathways as well as to elucidate the pathogenesis of migraine and the biological effects underlying the treatment of migraine with acupuncture. Proteomic and metabolomic profiling of plasma samples from patients with migraine without aura before and after acupuncture treatment revealed enrichment of immune-related pathway functions and the arginine synthesis pathway. Joint pathway analyses revealed significant enrichment of the pentose phosphate and glycolysis/gluconeogenesis pathways in patients with migraine. The glycolysis/gluconeogenesis and riboflavin metabolism pathways were significantly enriched after acupuncture treatment. The expression levels of various key proteins and metabolites, including α-D-glucose, flavin adenine dinucleotide, biliverdin reductase B, and L-glutamate, were significantly differentially expressed before and after acupuncture treatment in patients with migraine without aura. Treatment of migraine with acupuncture was associated with significant changes in key molecules and pathways, indicative of physiological changes in the trigeminovascular system, glutamate neurotoxicity, and other migraine-related physiological changes. Overall, our comprehensive analysis using proteomic and metabolomic profiling demonstrates that energy metabolism may serve as a key correlative link in the occurrence of migraine and the therapeutic effects of acupuncture treatment. Our findings may facilitate the identification of diagnostic and therapeutic modalities in the ongoing search for effective treatments for migraine attacks.

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The economic burden of low back pain in KwaZulu-Natal, South Africa: A prevalence-based cost-of-illness analysis from the healthcare provider’s perspective.

Low back pain (LBP) is a multifactorial and the most prevalent musculoskeletal disorder, whose economic burden is of global concern. Evidence suggests that the burden of LBP in increasing and will continue rising with the greatest burden occurring in low-and-middle-income-countries (LMICs). This study sought to determine the economic burden of LBP in KwaZulu-Natal, South Africa from the providers perspective.

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NSAID Hypersensitivity in the Pediatric Population: Classification and Diagnostic Strategies.

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently administered drugs, mainly for their anti-pyretic, but also for pain-relieving and anti-inflammatory effects in children. NSAIDs are composed of structurally divergent subgroups of drugs with similar pharmacological and adverse effects. Aspirin originates from salicin and was the first synthesized analgesic. As a prototype of NSAIDs; aspirin-induced hypersensitivity reactions were first reported, but subsequently, other phenotypes of hypersensitivity reactions were also described with aspirin and other NSAIDs. There are certain challenging aspects of NSAID-hypersensitivity in the pediatric population that need to be further investigated. These include the effect of age on drug metabolism and the natural history of the various phenotypes of NSAID-hypersensitivity, the effect of certain co-factors (infections, exercise) on NSAID-hypersensitivity, and diagnostic clinical and laboratory biomarkers clarifying the endotypes. In recent years, a non-negligible number of case series, studies and expert panel reports have been published in this field with some novel features and diagnostic modalities in the pediatric population. With the current review; the clinical phenotypes and diagnostic and management modalities of suspected NSAID-induced hypersensitivity reactions in childhood and adolescence were explained and updated by examining past and current publications.

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Prevalence of inverse psoriasis subtype with immune checkpoint inhibitors.

Cutaneous immune-related adverse events (irAEs) are the most common irAEs caused by immune-checkpoint inhibitors (ICI). Psoriasiform eruptions, both and flares, may occur. Evidence is lacking on inverse psoriasis subtype.

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The analgesic power of pleasant touch in individuals with chronic pain: Recent findings and new insights.

This mini-review covers recent works on the study of pleasant touch in patients with chronic pain (CP) and its potential use as a treatment. While experiments have demonstrated that pleasant touch, through the activation of CT-afferents and the brain regions involved in its affective value, might reduce the unpleasantness and intensity of induced pain, the interaction between pleasant touch and CP remains under-examined. Some experiments show that CP might disrupt the positive aspects of receiving pleasant touch, while in other studies the perception of pleasantness is preserved. Moreover, only a few attempts have been made to test whether touch can have a modulatory effect on CP, but these results also remain inconclusive. Indeed, while one recent study demonstrated that CT-touch can diminish CP after a short stimulation, another study suggested that pleasant touch might not be sufficient. Future studies should further investigate the psychological and neural interplay between pleasant touch and CP. In the conclusion of this mini-review, we propose a new tool we have recently developed using immersive virtual reality (IVR).

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