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Targeting N-type calcium channels in young-onset of some neurological diseases.

Calcium (Ca ) is an important second messenger in charge of many critical processes in the central nervous system (CNS), including membrane excitability, neurotransmission, learning, memory, cell proliferation, and apoptosis. In this way, the voltage-gated calcium channels (VGCCs) act as a key supply for Ca entry into the cytoplasm and organelles. Importantly, the dysregulation of these channels has been reported in many neurological diseases of young-onset, with associated genetic factors, such as migraine, multiple sclerosis, and Huntington's disease. Notably, the literature has pointed to the role of N-type Ca channels (NTCCs) in controlling a variety of processes, including pain, inflammation, and excitotoxicity. Moreover, several Ca channel blockers that are used for therapeutic purposes have been shown to act on the N-type channels. Therefore, this review provides an overview of the NTCCs in neurological disorders focusing mainly on Huntington's disease, multiple sclerosis, and migraine. It will discuss possible strategies to generate novel therapeutic strategies.

Efficacy and safety evaluation of dexmedetomidine for postoperative patient controlled intravenous analgesia: A systematic review and meta-analysis.

To investigate the efficacy and safety of dexmedetomidine (DEX) for postoperative patient controlled intravenous analgesia (PCIA). Two investigators independently searched Pubmed, Embase, Scopus, Cochrane Library and CBM for randomized controlled trials of DEX for PCIA. Thirty-seven studies with a total of 5,409 patients were included in this meta-analysis. Compared with analgesics alone, DEX for PCIA reduced pain score at 24 h [mean difference (MD) = -0.70; 95% confidence interval (CI): -0.85, -0.54; < 0.00001, = 90%] and 48 h postoperatively (MD = -0.43; 95% CI: -0.52, -0.34; < 0.00001, = 96%). Moreover, DEX reduced analgesics consumption during the first 24 h [standardized mean difference (SMD) = -0.25; 95% CI: -0.34, -0.16; < 0.00001, = 91%] and the number of resuscitation analgesics administered [odds ratio (OR) = 0.54; 95% CI: 0.44, 0.66; < 0.00001, = 72%]. Furthermore, DEX improved patient satisfaction (OR = 3.55; 95% CI: 2.36, 5.35; < 0.00001, = 60%), and reduced incidence of side effects, such as postoperative nausea and vomiting (PONV) (OR = 0.47; 95% CI: 0.39, 0.57; < 0.00001, = 59%) and pruritus after surgery (OR = 0.45; 95% CI: 0.30, 0.68; = 0.0001, = 0%). Besides, DEX attenuates inflammatory cytokine levels, such as IL-6 (MD = -5.73; 95% CI: -8.34, -3.12; < 0.00001, = 91%) and TNF-α (MD = -0.63; 95% CI: -0.76, -0.50; < 0.00001, = 89%). Finally, DEX increased the risk of bradycardia (OR = 1.66; 95% CI: 1.12, 2.45; = 0.01, = 15%), but the complication of hypotension did not differ between the two groups (OR = 1.30; 95% CI: 0.84, 2.04; = 0.25, = 0%). DEX is used for postoperative PCIA analgesia, which can significantly improve the analgesic effect, effectively control postoperative inflammatory response, reduce the dosage and adverse reactions of analgesics, and improve postoperative patient satisfaction. Of course, the impact of the immunosuppressive effect of DEX on the prognosis of patients needs further study. CRD42022340933, https://www.crd.york.ac.uk/prospero/.

The potential mechanisms and application prospects of non-coding RNAs in intervertebral disc degeneration.

Low back pain (LBP) is one of the most common musculoskeletal symptoms and severely affects patient quality of life. The majority of people may suffer from LBP during their life-span, which leading to huge economic burdens to family and society. According to the series of the previous studies, intervertebral disc degeneration (IDD) is considered as the major contributor resulting in LBP. Furthermore, non-coding RNAs (ncRNAs), mainly including microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), can regulate diverse cellular processes, which have been found to play pivotal roles in the development of IDD. However, the potential mechanisms of action for ncRNAs in the processes of IDD are still completely unrevealed. Therefore, it is challenging to consider ncRNAs to be used as the potential therapeutic targets for IDD. In this paper, we reviewed the current research progress and findings on ncRNAs in IDD: i). ncRNAs mainly participate in the process of IDD through regulating apoptosis of nucleus pulposus (NP) cells, metabolism of extracellular matrix (ECM) and inflammatory response; ii). the roles of miRNAs/lncRNAs/circRNAs are cross-talk in IDD development, which is similar to the network and can modulate each other; iii). ncRNAs have been attempted to combat the degenerative processes and may be promising as an efficient bio-therapeutic strategy in the future. Hence, this review systematically summarizes the principal pathomechanisms of IDD and shed light on the therapeutic potentials of ncRNAs in IDD.

Characteristics of vestibular migraine, probable vestibular migraine, and recurrent vertigo of childhood in caloric and video head impulse tests.

Vertigo is very common in children, but the specific diagnosis and characteristics are not clear. The main objective of this study was to analyze the characteristics of caloric test (CT) and video head impulse test (vHIT) in vestibular migraine of childhood (VMC), probable vestibular migraine of childhood (PVMC), and recurrent vertigo of childhood (RVC), which can provide a reference value for their clinical diagnosis.

Modulation of colonic function in irritable bowel syndrome rats by electroacupuncture at ST25 and the neurobiological links between ST25 and the colon.

Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disease characterized by abdominal pain and defecation disorders. Acupuncture therapy positively affects IBS, with ST25 being the main point. However, ST25 has mostly been used in conjunction with other acupoints. This study aimed to observe the therapeutic effect of electroacupuncture at ST25 alone in IBS and the neurobiological mechanism of ST25 associated with the colon. First, we observed the effect of electroacupuncture at ST25 on the visceral pain threshold and slow-wave discharge of the colon in IBS model rats. Second, we explored the neurobiological mechanism of ST25 associated with the colon using a neural tracer technique. The results showed that (1) electroacupuncture at ST25 alone can alleviate visceral hypersensitivity and restore normal slow-wave frequency and rhythm of the colon in IBS rats; (2) there is a close neuroanatomical connection between ST25 and the colon, i.e., in the dorsal root ganglion (DRG), ST25 is similar in innervation to the colon, mainly in the T8-L1 segment, while the presence of double-labeled positive neurons is present in a part of the DRG; retrogradely labeled motor neurons associated with ST25 were observed in the anterior horn of the spinal cord, and retrogradely labeled sympathetic postganglionic neurons associated with ST25 were observed in the sympathetic nerve chain. These findings suggested that the DRGs and the dorsal horn of the spinal cord are important targets for electroacupuncture at ST25 to reduce visceral hypersensitivity in IBS rats. The sympathetic ganglia may be an important site for ST25 to regulate intestinal motility. The neurobiological mechanism of ST25 action in IBS rats should be further investigated in the future by combining related techniques, such as pseudorabies virus, optogenetics, calcium imaging, and electrophysiology.

Efficacy of repetitive transcranial magnetic stimulation on chronic migraine: A meta-analysis.

Migraine is a neurovascular disorder that affects the quality of life of more than 1 billion people worldwide. Repetitive transcranial magnetic stimulation (rTMS) is a neuromodulation tool that uses pulsed magnetic fields to modulate the cerebral cortex. This meta-analysis ascertained the therapeutic or preventive effect of rTMS on chronic migraine.

Effect of music intervention on subjective scores, heart rate variability, and prefrontal hemodynamics in patients with chronic pain.

Music interventions have been proposed in recent years as a treatment for chronic pain. However, the mechanisms by which music relieves pain are unclear, and the effects of music intervention on physiological indicators in patients with chronic pain remain to be explored. This study aimed to explore whether a music intervention would have effects on subjective pain ratings, heart rate variability, and functional connectivity of the cerebral cortex in patients with chronic pain.

Opioid and gabapentinoid prescriptions in England from 2015 to 2020.

Concerns gradually arose about misuse of gabapentinoids (gabapentin and pregabalin), especially when used in combination with opioids. Because it can be a driver of usage, trends in prescribing habits may be interesting to analyse. The aim of this study is to examine the evolution of prescriptions of opioids and gabapentinoids in England from 2015 to 2020 at a regional level.

Are inflammatory parameters an independent predictor of hip osteoarthritis severity? A prospective cross-sectional study.

This study aimed to investigate the relationship between the presence of hip osteoarthritis and the neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, monocyte-lymphocyte ratio, and neutrophil-monocyte ratio.

Pilot comparison of outcome measures across chemical and surgical experimental models of chronic osteoarthritis in the rat (Rattus norvegicus).

Relatively little work has evaluated both the disease of osteoarthritis (OA) and clinically-relevant pain outcome measures across different OA models in rats. The objective of this study was to compare sensitivity, pain, and histological disease severity across chemical and surgical models of OA in the rat. Stifle OA was induced in Sprague-Dawley rats via intraarticular injection of monoiodoacetate (MIA) or surgical transection of anterior cruciate ligament and/or destabilization of medial meniscus (ACL+DMM or DMM alone). Reflexive (e.g., mechanical and thermal stimuli) measures of sensitivity and non-reflexive assays (e.g., lameness, static hindlimb weight-bearing asymmetry, dynamic gait analysis) of pain were measured over time. Joint degeneration was assessed histologically. Six-weeks post OA-induction, the ACL+DMM animals had significantly greater visually observed lameness than MIA animals; however, both ACL+DMM and MIA animals showed equal pain as measured by limb use during ambulation and standing. The MIA animals showed increased thermal, but not mechanical, sensitivity compared to ACL+DMM animals. Joint degeneration was significantly more severe in the MIA model at 6 weeks. Our pilot data suggest both the ACL+DMM and MIA models are equal in terms of clinically relevant pain behaviors, but the MIA model is associated with more severe histological changes over time potentially making it more suitable for screening disease modifying agents. Future work should further characterize each model in terms of complex pain behaviors and biochemical, molecular, and imaging analysis of the sensory system and joint tissues, which will allow for more informed decisions associated with model selection and investigative outcomes.

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