YokoCo

Peripheral nerve stimulation (PNS) has been utilized for over 50 years with accumulating evidence of efficacy in a variety of chronic pain conditions. The level and strength of evidence supporting the use of PNS for peripheral neuropathic pain remains unclear. The purpose of this review is to synthesize data from prospective studies on the efficacy of PNS for neuropathic pain as it pertains to pain intensity, neurological deficits/neuropathy (e.g., weakness, sensory deficits, gait/balance), and other secondary outcomes (quality of life, satisfaction, emotional functioning, and adverse events). In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, this review identified articles from MEDLINE(R), EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus. Overall, per the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria, pooled results demonstrate very low quality or low quality of evidence supporting modest to substantial improvement in pain and neurological function after PNS implantation for treatment of peripheral neuropathic pain. PNS for phantom limb pain was the only indication that had moderate level evidence. Future prospective and well-powered studies are warranted to assess the efficacy of PNS for peripheral neuropathic pain.

Neurological and psychiatric patients have increased dramatically in number in the past few decades. However, effective treatments for these diseases and disorders are limited due to heterogeneous and unclear pathogenic mechanisms. Therefore, further exploration of the biological aspects of the disease, and the identification of novel targets to develop alternative treatment strategies, is urgently required. Systems-level investigations have indicated the potential involvement of the brain-gut axis and intestinal microbiota in the pathogenesis and regulation of neurological and psychiatric disorders. While intestinal microbiota is crucial for maintaining host physiology, some important sensory and regulatory cells in the host should not be overlooked. Intestinal epithelial enteroendocrine cells (EECs) residing in the epithelium throughout intestine are the key regulators orchestrating the communication along the brain-gut-microbiota axis. On one hand, EECs sense changes in luminal microorganisms via microbial metabolites; on the other hand, they communicate with host body systems via neuroendocrine molecules. Therefore, EECs are believed to play important roles in neurological and psychiatric disorders. This review highlights the involvement of EECs and subtype cells, via secretion of endocrine molecules, in the development and regulation of neurological and psychiatric disorders, including Parkinson's disease (PD), schizophrenia, visceral pain, neuropathic pain, and depression. Moreover, the current paper summarizes the potential mechanism of EECs in contributing to disease pathogenesis. Examination of these mechanisms may inspire and lead to the development of new aspects of treatment strategies for neurological and psychiatric disorders in the future.

In November 2018, the UK's Home Office established a legal route for eligible patients to be prescribed cannabis-based products for medicinal use in humans (CBPMs) as unlicensed medicines. These include liquid cannabis extracts for oral administration ("oils") and dried flowers for inhalation ("flos"). Smoking of CBPMs is expressly prohibited. To date, THC-predominant cannabis flowers remain the most prescribed CBPMs in project Twenty21 (T21), the first multi-center, prospective, observational UK cannabis patient registry. This observational, prospective data review analyzes patient-reported outcome measures (PROMS) collected by T21 associated with the inhalation of KHIRON 20/1, the most prescribed CBPM in the project. PROMS collected at baseline and at subsequent 3-month follow-up included health-related quality of life (HRQoL), general mood, and sleep. Condition-specific measures of illness severity were performed with the Brief Pain Inventory Short Form (BPI-SF) and the Generalized Anxiety Disorder 7-Item Scale (GAD-7). Participants (N = 344) were mostly males (77.6%, average age = 38.3) diagnosed mainly with chronic pain (50.9%) and anxiety-related disorders (25.3%). Inhalation of KHIRON 20/1 was associated with a marked increase in self-reported HRQoL, general mood, and sleep (N = 344; < 0.001). Condition-specific assessments showed significant improvements in pain severity (T = 6.67; < 0.001) and interference (T = 7.19; < 0.001) in patients using KHIRON 20/1 for chronic pain (N = 174). Similar results were found for patients diagnosed with anxiety-related disorders (N = 107; T = 12.9; < 0.001). Our results indicate that controlled inhalation of pharmaceutical grade, THC-predominant cannabis flos is associated with a significant improvement in patient-reported pain scores, mood, anxiety, sleep disturbances and overall HRQoL in a treatment-resistant clinical population.

Pain after an acute Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) condition (post-COVID pain) is becoming a new healthcare emergency. Precision medicine refers to an evidence-based method of grouping patients based on their diagnostic/symptom presentation and then tailoring specific treatments accordingly. Evidence suggests that post-COVID pain can be categorized as nociceptive (i.e., pain attributable to the activation of the peripheral receptive terminals of primary afferent neurons in response to noxious chemical, mechanical, or thermal stimuli), neuropathic (i.e., pain associated with a lesion or disease of the somatosensory nervous system and limited to a "neuroanatomically plausible" distribution of the system), nociplastic (i.e., pain arising from altered nociception despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors or evidence for disease or lesion of the somatosensory system causing the pain), or mixed type (when two pain phenotypes co-exist). Each of these pain phenotypes may require a different treatment approach to maximize treatment effectiveness. Accordingly, the ability to classify post-COVID pain patients into one of these phenotypes would likely be critical for producing successful treatment outcomes. The 2021 International Association for the Study of Pain (IASP) clinical criteria and grading system provide a framework for classifying pain within a precision pain medicine approach. Here we present data supporting the possibility of grouping patients with post-COVID pain into pain phenotypes, using the 2021 IASP classification criteria, with a specific focus on nociplastic pain, which is probably the primary mechanism involved in post-COVID pain. Nociplastic pain, which is usually associated with comorbid symptomology (e.g., poor sleep quality, fatigue, cognitive-emotional disturbances, etc.) and is considered to be more difficult to treat than other pain types, may require a more nuanced multimodal treatment approach to achieve better treatment outcomes.

On the slow path to improving the life expectancy and quality of life of patients post spinal cord injury (SCI), recovery remains controversial. The potential role of the regenerative capacity of the nervous system has led to numerous attempts to stimulate the SCI to re-establish the interrupted sensorimotor loop and to understand its potential in the recovery process. Numerous resources are now available, from pharmacological to biomolecular approaches and from neuromodulation to sensorimotor rehabilitation interventions based on the use of various neural interfaces, exoskeletons, and virtual reality applications. The integration of existing resources seems to be a promising field of research, especially from the perspective of improving living conditions in the short to medium term. Goals such as reducing chronic forms of neuropathic pain, regaining control over certain physiological activities, and enhancing residual abilities are often more urgent than complete functional recovery. In this perspective article, we provide an overview of the latest interventions for the treatment of SCI through broad phases of injury rehabilitation. The underlying intention of this work is to introduce a spinal cord neuroplasticity-based multimodal approach to promote functional recovery and improve quality of life after SCI. Nonetheless, when used separately, biomolecular therapeutic approaches have been shown to have modest outcomes.

Endometriosis is a benign chronic disease in women that is characterized by the presence of active foci of the endometrium or endometrial tissue occurring outside of the uterus. The disease causes disabling symptoms such as pelvic pain and infertility, which negatively affect a patient's quality of life. In addition, endometriosis imposes an immense financial burden on the healthcare system. At present, laparoscopy is the gold standard for diagnosing the disease because other non-invasive diagnostic tests have less accuracy. In addition, other diagnostic tests have low accuracy. Therefore, there is an urgent need for the development of a highly sensitive, more specific, and non-invasive test for the early diagnosis of endometriosis. Numerous researchers have suggested miRNAs as potential biomarkers for endometriosis diagnosis due to their specificity and stability. However, the greatest prognostic force is the determination of several miRNAs, the expression of which varies in a given disease. Despite the identification of several miRNAs, the studies are investigatory in nature, and there is no consensus on them. In the present review, we first provide an introduction to the dysregulation of miRNAs in patients with endometriosis and the potential use of miRNAs as biomarkers in the detection of endometriosis. Then we will describe the role of the mir-200 family in endometriosis. Several studies have shown that the expression of the mir-200 family changes in endometriosis patients, suggesting that they could be used as a diagnostic biomarker and therapeutic target for endometriosis.

Neuropathic pain is a condition that impacts a substantial portion of the population and is expected to affect a larger percentage in the future. This type of pain is poorly managed by current therapies, including opioids and NSAIDS, and novel approaches are needed. We used a cisplatin-induced model of neuropathic pain in mice to assess the effects of the cannabinoids THC and CBD alone or in varying ratios as anti-nociceptive agents. In addition to testing pure compounds, we also tested extracts containing high THC or CBD at the same ratios. We found that pure CBD had little impact on mechanical hypersensitivity, whereas THC reduced mechanical hypersensitivity in both male and female mice (as has been reported in the literature). Interestingly, we found that high CBD cannabis extract, at the same CBD dose as pure CBD, was able to reduce mechanical hypersensitivity, although not to the same level as high THC extract. These data suggest that, at least for CBD-dominant cannabis extracts, there is an increase in the anti-nociceptive activity that may be attributed to other constitutes of the plant. We also found that high THC extract or pure THC is the most efficacious treatment for reducing neuropathic pain in this model.

Despite the large body of research on sex differences in pain, there is a lack of translation to real-world pain management. Our aim was to analyse the sex differences in the analgesic response to oxycodone/naloxone (OXN) and tapentadol (TAP), in comparison with other opioids (OPO) commonly prescribed for chronic non-cancer pain (CNCP). An observational and cross-sectional study was conducted on ambulatory CNCP patients ( = 571). Sociodemographic, clinical (pain intensity, relief, and quality of life), safety (adverse events (AEs), adverse drug reactions), hospital frequentations and pharmacological (morphine equivalent daily dose (MEDD)) variables were collected. Multiple linear regressions were carried out to assess the association between sex and outcomes. Sex differences were observed, with lower female tolerability and higher hospital frequentation, especially in the OXN group (OR AEs report = 2.8 [1.8-4.4], < 0.001). Here, females showed higher hospital use (23% hospital admission, 30% prescription change, < 0.05), requiring a higher MEDD (127 ± 103 mg/day, < 0.05), compared to OXN men. Regardless of the opioid group, CNCP women were significantly older than men (three years), with significantly higher benzodiazepine use (OR = 1.6 [1.1-2.3]), more constipation (OR = 1.34 [0.93-1.90]) and headache (OR = 1.45 [0.99-2.13]) AEs, than men who were more likely to refer sexual dysfunction (OR = 2.77 [1.53-5.01]), and loss of libido (OR = 1.93 [1.22-3.04]). Sex-differences were found related to poorer female drug tolerability and higher hospital resources, even worst in OXN female users. Other differences related to older female ages and benzodiazepine prescription, need to be further analysed from a gender perspective.

: Adequate pain control is of crucial importance to patient recovery and satisfaction following abdominal surgeries. The optimal analgesia regimen remains controversial in liver resections. : Three groups of patients undergoing open hepatectomies were retrospectively analyzed, reviewing intravenous patient-controlled analgesia (IV-PCA) versus IV-PCA in addition to bilateral rectus sheath and subcostal transversus abdominis plane nerve blocks (IV-PCA + NBs) versus patient-controlled thoracic epidural analgesia (TEA). Patient-reported pain scores and clinical data were extracted and correlated with the method of analgesia. Outcomes included total morphine consumption and numerical rating scale (NRS) at rest and on movement over the first three postoperative days, time to remove the nasogastric tube and urinary catheter, time to commence on fluid and soft diet, and length of hospital stay. : The TEA group required less morphine over the first three postoperative days than IV-PCA and IV-PCA + NBs groups (9.21 ± 4.91 mg, 83.53 ± 49.51 mg, and 64.17 ± 31.96 mg, respectively, < 0.001). Even though no statistical difference was demonstrated in NRS scores on the first three postoperative days at rest and on movement, the IV-PCA group showed delayed removal of urinary catheter (removal on postoperative day 4.93 ± 5.08, 3.87 ± 1.31, and 3.70 ± 1.30, respectively) and prolonged length of hospital stay (discharged on postoperative day 12.71 ± 7.26, 11.79 ± 5.71, and 10.02 ± 4.52, respectively) as compared to IV-PCA + NBs and TEA groups. : For postoperative pain management, it is expected that the TEA group required the least amount of opioid; however, IV-PCA + NBs and TEA demonstrated comparable postoperative outcomes, namely, the time to remove nasogastric tube/urinary catheter, to start the diet, and the length of hospital stay. IV-PCA with NBs could thus be a reliable analgesic modality for patients undergoing open liver resections.

The pathophysiology of interstitial cystitis/bladder pain syndrome (IC/BPS) is multifactorial. Identifying the clinical characteristics and cystoscopic findings of bladder-centered IC/BPS facilitates optimal treatment strategies targeting the diseased urinary bladder. Patients with Hunner's lesion (HIC) and without Hunner's lesion (NHIC) should be treated differently. Based on the histopathological findings, NHIC can be treated with intravesical instillation of urothelial protective agents, such as hyaluronic acid, to cover the urothelial defects. In non-responders, chronic inflammation and higher urothelial dysfunction can be treated with intravesical botulinum toxin A injection, platelet-rich plasma injection, or low-energy shock wave treatment to reduce inflammation, increase tissue regeneration, and improve the urothelial barrier. Patients with HIC should be treated with electrocauterization first; augmentation enterocystoplasty should only be used in end-stage HIC when the contracted bladder is refractory to other treatments. The antiviral agent, valacyclovir, can be used in patients with HIC, small bladder capacity, and high-grade glomerulations. In addition, behavioral modification is always recommended from the beginning of treatment. Treatment with cognitive behavioral therapy interventions in combination with bladder therapy can reduce anxiety and improve treatment outcomes. Herein, recent advances in the pathophysiology and novel treatments for IC/BPS are reviewed.