YokoCo

Neurostimulation-based therapeutic approaches are emerging as alternatives to pharmacological drugs, but need further development to optimize efficacy and reduce variability. Despite its key relevance to pain, the insular cortex has not been explored in cortical neurostimulation approaches. Here, we developed an approach to perform repetitive transcranial direct current stimulation of the posterior insula (PI tDCS) and studied its impact on sensory and aversive components of neuropathic pain and pain-related anxiety and the underlying neural circuitry in mice using behavioral methods, pharmacological interventions and the expression of the activity-induced gene product, Fos. We observed that repetitive PI tDCS strongly attenuates the development of neuropathic mechanical allodynia and also reverses chronically established mechanical and cold allodynia for several weeks post-treatment by employing descending opioidergic antinociceptive pathways. Pain-related anxiety, but not pain-related aversion, were inhibited by PI tDCS. These effects were associated with a long-term suppression in the activity of key areas involved in pain modulation, such as the cingulate, prefrontal and motor cortices. These data uncover the significant potential of targeting the insular cortex with the objective of pain relief and open the way for more detailed mechanistic analyses that will contribute to improving cortical neurostimulation therapies for use in the clinical management of pain.

Febrile seizure (FS) is a common type of seizure occurring in human during infancy and childhood. Although an epileptic seizure is associated with psychiatric disorders and comorbid diseases such as depression, anxiety, autism spectrum disorders, sleep disorders, attention deficits, cognitive impairment, and migraine, the causal relationship between FS and psychiatric disorders is poorly understood. The objective of the current study was to investigate the relationship of FS occurrence in childhood with the pathogenesis of anxiety disorder and depression using an FS rat model. We induced febrile seizures in infantile rats (11 days postnatal) using a mercury vapor lamp. At 3 weeks and 12 weeks after FS induction, we examined behaviors and recorded local field potentials (LFPs) to assess anxiety and depression disorder. Interestingly, after FS induction in infantile rats, anxiogenic behaviors and depression-like phenotypes were found in both adult and juvenile FS rats. The analysis of LFPs revealed that 4-7 Hz hippocampal theta rhythm, a neural oscillatory marker for anxiety disorder, was significantly increased in FS rats compared with their wild-type littermates. Taken together, our findings suggest that FS occurrence in infants is causally related to increased levels of anxiety-related behaviors and depression-like symptoms in juvenile and adult rodents.

Pannexin1 (Panx1) is expressed in both neurons and glia where it forms ATP-permeable channels that are activated under pathological conditions such as epilepsy, migraine, inflammation, and ischemia. Membrane lipid composition affects proper distribution and function of receptors and ion channels, and defects in cholesterol metabolism are associated with neurological diseases. In order to understand the impact of membrane cholesterol on the distribution and function of Panx1 in neural cells, we used fluorescence recovery after photobleaching (FRAP) to evaluate its mobility and electrophysiology and dye uptake to assess channel function. We observed that cholesterol extraction (using methyl-β-cyclodextrin) and inhibition of its synthesis (lovastatin) decreased the lateral diffusion of Panx1 in the plasma membrane. Panx1 channel activity (dye uptake, ATP release and ionic current) was enhanced in cholesterol-depleted Panx1 transfected cells and in wild-type astrocytes compared to non-depleted or Panx1 null cells. Manipulation of cholesterol levels may, therefore, offer a novel strategy by which Panx1 channel activation might modulate various pathological conditions.

(1) Background: Patients diagnosed with chronic pain suffer from long-term pain, which negatively affects their daily lives and mental health. Virtual reality (VR) technologies are considered a therapeutic tool to manage pain perception and mental health conditions. This systematic review aimed to appraise the efficacy of VR in improving pain intensity, anxiety, depression and mood among patients with chronic pain; (2) Methods: Five electronic databases were systematically searched using the terms representing VR and chronic pain. Quality assessment was conducted using Cochrane Collaboration's tool and Newcastle-Ottawa scale; (3) Results: Seventeen peer-reviewed articles were included in this review. It was found that VR was able to reduce pain intensity in patients with phantom limb pain, chronic headache, chronic neck pain and chronic low-back pain. The effects of VR on the improvement of anxiety, depression and mood were not determined due to the inadequate amount of clinical evidence; (4) Conclusions: VR, especially immersive VR, improves pain outcomes and its effects may vary depending on the approach and study design. More research is still needed to investigate the clinical use of VR in patients with chronic pain.

Nonsteroidal anti-inflammatory drugs (NSAIDs) and analgesics are the most commonly used drugs worldwide and their availability over-the-counter is increasing. The aim of this study was to examine the frequency of their use as well as the awareness of the associated risk of side effects in patients with chronic kidney disease (CKD) compared to the patients at general practice (GP) offices. We found that 88.5% of the CKD and 97.1% of the GP group used NSAIDs and/or analgesics ( < 0.0001). Paracetamol was chosen the most often by both study groups, but the proportion of patients taking paracetamol was significantly higher in the CKD group ( < 0.006). On the contrary, the proportion of patients taking ibuprofen was significantly higher in GP group ( < 0.0001). Furthermore, almost 37% of CKD and 60% of GP patients never consult with their doctor before taking NSAIDs or analgesics. The influence of advertisements on the decision to take these drugs was found to be marginal in both groups. In conclusion, the NSAIDs and/or analgesics use is very common. The differences between the studied cohorts in self-decision making and the type of drugs used between the studied cohorts warrant tailored educational approaches.

Stress urinary incontinence (SUI) represents one of the most common subtypes of urinary incontinence (UI) reported by women. Studies have shown an association of SUI with nonspecific low back pain (NSLBP). The primary aim of the present study was to explore the long-term effects of a combined treatment of manual techniques and pelvic floor muscle (PFM) training in women suffering from SUI associated with NSLBP. The secondary aim was to evaluate which manual approach combined with PFM rehabilitation is more effective in improving symptoms related to SUI and in reducing pain perception related to NSLBP. Twenty-six patients suffering from SUI associated with chronic NSLBP were randomly assigned to one of two groups: the postural rehabilitation group (PRg) or the spinal mobilization group (SMg). Both groups performed a manual approach combined with PFM rehabilitation. All patients were evaluated before the treatment (T0), after 10 sessions (T1) and after 30 days from the end of the treatment (T2). The results showed an improvement in both groups in all of the investigated outcomes. Combining manual therapy and PFM training within the same therapy session may be useful for improving both SUI and NSLBP and increasing the quality of life of women suffering from SUI associated with NSLBP.

Clavicle fracture fixation is commonly performed under general anesthesia due to the complex sensory innervation in this region which poses a challenge for anesthesiologists applying regional anesthetic (RA) techniques. In part 1 of this two-part study, we summarized the current literature describing various RA approaches in clavicle fractures and surgery. In our earlier scoping review, we surmised that a superficial or intermediate cervical plexus block (CPB) may provide analgesia for this procedure and, when combined with an interscalene brachial plexus block (ISB), can provide anesthesia to the clavicular region for surgical fixation. We performed a retrospective study, consolidating assumptions that were based on the results of our earlier scoping review. A retrospective study was conducted on 168 consecutive patients who underwent clavicle fixation surgery at a tertiary healthcare system in Singapore. We used a standardized to collate perioperative data from the electronic health records of both hospitals, including anesthetic technique, analgesic requirements, pain scores, and adverse events, up to the second postoperative day or up until discharge. In our study, patients who received RA had significantly reduced pain scores and opioid requirements, compared to general anesthesia (GA) alone. Through subgroup analysis, differences were found in postoperative pain scores and opioid requirements in the following order: GA alone > GA with local infiltration analgesia > CPB > CPB plus ISB. All patients who received combined CPB and ISB had upper limb weakness in recovery, compared to none with CPB alone ( < 0.001). Of those who received an ISB either in isolation or combined with a CPB, four (9.3%) were reported to have dyspnea (within 24 h) and motor weakness that persisted beyond 12 h, compared to none for patients that received CPB alone. Addition of a CPB to GA for clavicle fracture fixation surgery is associated with reduced pain scores in the early postoperative period, with a lower opioid requirement compared to GA alone. In patients undergoing GA, the combination of a CPB with an ISB was associated with a small, although statistically significant, reduction in pain scores and opioid requirements compared to a CPB alone.

Fibromyalgia (FM) is a chronic pain syndrome with an unclear etiology. In addition to pain, FM patients suffer from a diverse array of symptoms and comorbidities, encompassing fatigue, cognitive dysfunction, mood disorders, sleep deprivation, and dizziness. Due to the complexity of FM, the diagnosis and treatment of it are highly challenging. The aim of the present work was to investigate some clinical and psychological characteristics of FM patients, and to uncover possible correlations with pharmacological and non-pharmacological therapies. We conducted a cross-sectional, questionnaire-based study aimed at evaluating pain, psychological traits, and the self-perceived effectiveness of pharmacological and non-pharmacological treatments in an Italian population of FM patients. Descriptive statistics, correlation, and inference analyses were performed. We found a prevalence of a neuropathic/nociplastic type of pain, which correlated with psychological traits such as anxiety, low mood, psychophysical discomfort, and the inability to relax. The pain type and psychological traits proved to play a role in determining the self-perceived effectiveness of therapeutic interventions. Patients revealed a better response to non-pharmacological therapies, particularly dietary interventions, relaxation techniques, and psychotherapy rather than pharmacological interventions. The sum of our data indicates that for better outcomes, the type of pain and psychological traits should be considered for tailor-made treatments considering non-pharmacological protocols as a complement to the use of drugs.

Chronic low-back pain (CLBP) is a common disease with several negative consequences on the quality of life, work and activity ability and increased costs to the health-care system. When pharmacological, psychological, physical and occupational therapies or surgery fail to reduce CLBP, patients may be a candidate for Spinal Cord Stimulation (SCS). SCS consists of the transcutaneous or surgical implantation of different types of electrodes in the epidural space; electrodes are then connected to an Implanted Pulse Generator (IPG) that generates stimulating currents. Through spinal and supraspinal mechanisms based on the "gate control theory for pain transmission", SCS reduces symptoms of CLBP in the almost totality of well-selected patients and its effect lasts up to eight years in around 75% of patients. However, the evidence in favor of SCS still remains weak, mainly due to poor trial methodology and design. This narrative review is mainly addressed to those professionals that may encounter patients with CLBP failing conventional treatments. For this reason, we report the mechanisms of pain relief during SCS, the technical features and some clinical considerations about the application of SCS in patients with CLBP.

Multiple sclerosis (MS) represents a major cause of chronic neurological disability in young adults and can result in upper limb sensorimotor impairment with a huge impact on manual dexterity and activities of daily living. Moreover, pain is common in MS and a large proportion of patients suffer from central neuropathic pain. To date, no rehabilitative treatment has been described as useful for these patients. A 46-year-old woman, affected by relapsing-remittent MS, described a one-year history of right shoulder pain (Visual Analogue Scale = 8) that started gradually and without trauma. The patient also presented balance and gait impairments, upper limb strength deficit, and fatigue (Expanded Disability Status Scale = 5.5). A multidisciplinary treatment was proposed, including three intra-articular corticosteroid injections and one month of manual therapy, three sessions/week, based on proprioceptive neuromuscular facilitation for the upper limb. At the end of the rehabilitative treatment, pain relief and an improvement in the range of motion of the affected shoulder, upper limb muscle strength, and hand dexterity were observed. The present paradigmatic case report with literature review demonstrated that a multidisciplinary approach seems to be effective in pain relief in a patient with central neuropathic shoulder pain and relapsing-remitting MS.