Accepted

Our current understanding of central nervous system mechanisms supporting the experience of pain remains remarkably limited and produces substantial challenges when seeking to better diagnose and treat chronic pain. A new conceptual framework – The Distributed Nociceptive System – emphasizes system-level aspects of nociceptive processing by incorporating population coding and distributed process. The Distributed Nociceptive System provides a structure for understanding complex spatial aspects of chronic pain and provides a clear rationale for the further development of multi-disciplinary treatments for chronic pain.

Diabetic peripheral neuropathy (DPN) is a common neurological complication of diabetes mellitus without efficient interventions. Both lysine demethylase 5B (KDM5B) and sirtuin-3 (SIRT3) have been found to regulate islet function and glucose homeostasis. KDM5B was predicted to bind to the SIRT3 promoterby bioinformatics. Here, we investigated whether KDM5B affected DPN development via modulating SIRT3.

Trigeminal Neuralgia (TN) is an excruciating unilateral facial pain, which negatively affects patient's quality of life. Historically, it has been difficult to compare treatment efficacy due to the lack of standardized outcomes. In addition, patients' perspective has seldomly been acknowledged. The aim of this study was to reach consensus on what outcomes of treatment are important to different TN stakeholders (patients, clinicians and researchers), to identify the TN Core Outcome Set (TRINCOS).

Allodynia and hyperalgesia are common signs in individuals with complex regional pain syndrome (CRPS), mainly attributed to sensitization of the nociceptive system. Appropriate diagnostic tools for the objective assessment of such hypersensitivities are still lacking, which are essential for the development of mechanism-based treatment strategies.

Chronic nausea and vomiting syndromes (NVSs) are prevalent and debilitating disorders. Putative mechanisms include gastric neuromuscular disease and dysregulation of brain-gut interaction, but clinical tests for objectively defining gastric motor function are lacking. A medical device enabling noninvasive body surface gastric mapping (BSGM) was developed and applied to evaluate NVS pathophysiology. BSGM was performed in 43 patients with NVS and 43 matched controls using Gastric Alimetry (Alimetry), a conformable high-resolution array (8 × 8 electrodes; 20-mm interelectrode spacing), wearable reader, and validated symptom-logging app. Continuous measurement encompassed a fasting baseline (30 minutes), 482-kilocalorie meal, and 4-hour postprandial recording, followed by spectral and spatial biomarker analyses. Meal responses were impaired in NVS, with reduced amplitudes compared to controls (median, 23.3 microvolts versus 38.0 microvolts, < 0.001), impaired fed-fasting power ratios (1.1 versus 1.6, = 0.02), and disorganized slow waves (spatial frequency stability, 13.6 versus 49.5; < 0.001). Two distinct NVS subgroups were evident with indistinguishable symptoms (all > 0.05). Most patients (62%) had normal BSGM studies with increased psychological comorbidities (43.5% versus 7.7%; = 0.03) and anxiety scores (median, 16.5 versus 13.0; = 0.035). A smaller subgroup (31%) had markedly abnormal BSGM, with biomarkers correlating with symptoms (nausea, pain, excessive fullness, early satiety, and bloating; all > 0.35, < 0.05). Patients with NVS share overlapping symptoms but comprise distinct underlying phenotypes as revealed by a BSGM device. These phenotypes correlate with symptoms, which should inform clinical management and therapeutic trial design.

The inclusion of certain variables in remission formulas for rheumatoid arthritis (RA) may give rise to discrepancies. An increase in patient global assessment (PGA), a variable showing the patient's self-evaluation of their disease activity, may alone tilt a patient out of remission when using certain remission-assessing methods. This study aimed to explore differences in remission rates among various formulas and the impact of PGA and other clinical variables on the calculation of remission.

(1) : The aim of this narrative review was to analyze the neuroanatomical and neurophysiological basis of cervicogenic pain in cervico-cranial pain syndromes, focusing particularly on cervico-orofacial syndromes as a background for the proper diagnosis and non-surgical treatment. Relevant literature on the topic from past 120 years has been surveyed. (2) : We surveyed all original papers, reviews, or short communications published in the English, Spanish, Czech or Slovak languages from 1900 to 2020 in major journals. (3) : The cervicogenic headache originates from the spinal trigeminal nucleus where axons from the C-C cervical spinal nerves and three branches of the trigeminal nerve converge (trigeminocervical convergence) at the interneurons that mediate cranio-cervical nociceptive interactions. The role of the temporomandibular joint in the broad clinical picture is also important. Despite abundant available experimental and clinical data, cervicogenic orofacial pain may be challenging to diagnose and treat. Crucial non-surgical therapeutic approach is the orthopedic manual therapy focused on correction of body posture, proper alignment of cervical vertebra and restoration of normal function of temporomandibular joint and occlusion. In addition, two novel concepts for the functional synthesis of cervico-cranial interactions are the tricentric concept of mouth sensorimotor control and the concept of a cervicogenic origin of bruxism. (4) : Understanding the basis of neuroanatomical and neurophysiological neuromuscular relations enables an effective therapeutic approach based principally on orthopedic manual and dental occlusal treatment.

Management of cancer pain is challenging. Despite the poor evidence, opioid therapy still remains the cornerstone for the management of cancer-related pain. Opioids should be given according to the clinical presentation in the different stages of disease. There is no drug of choice, as most opioids are effective. Thus, the choice should be based on the individual characteristics of patients. Optimization of opioid therapy may allow individual treatment according to the patient's characteristics and pain syndromes, providing timely alternatives in the different stages of disease. While most patients respond to an appropriate treatment associated with a comprehensive assessment and symptom control, a high level of experience and knowledge is necessary in determining conditions to maximize the analgesic response, eventually adding adjuvants in some specific circumstances. Alternative opioids may improve the balance between analgesia and adverse effects in the presence of a poor response to the first opioid in a large number of patients. Finally, a selected population can benefit from some interventional procedures.