Background/Objectives: Chronic primary pain (CPP) is a new diagnostic category including chronic pain conditions lacking clinical signs or a clear etiopathogenetic origin. These disorders may share a common neural mechanism known as central sensitization, where nociceptive neurons become hyper-responsive to standard or subthreshold pain stimuli, resulting in pain hyper-sensitivity. In this context, non-invasive brain stimulation (NIBS) appears to be a promising tool for improving CPP symptoms by targeting maladaptive brain activity and connectivity. To date, the effects of NIBS on CPP symptoms remain unexplored. To fill this gap, we conducted a meta-analysis, investigating the effect of NIBS in improving the three core symptoms of CPP, namely pain intensity, emotional distress, and functional disability. Methods: Following PRISMA guidelines, we screened four databases up to February 2025 for English-language, peer-reviewed randomized clinical trials that included CPP patients treated with NIBS and reported pre/post or follow-up scores on validated measures of at least one core symptom. Quality of life was examined as an additional outcome. Results: Fifty-four studies were included, with 1371 participants receiving real stimulation and 1103 sham. Findings highlighted that real stimulation improved CPP symptoms immediately after treatment and at one-month follow-up. Meta-regressions showed that longer CPP duration reduced short-term effects on emotional distress and diminished all outcomes at one-month follow-up. Conclusions: Further research is needed to establish standardized NIBS protocols for CPP management, to investigate the effectiveness at longer follow-up periods, and to test whether combining NIBS with other interventions enhances treatment effectiveness and durability.

Background: This study aimed at identifying neuropsychological sub‐phenotypes in amyotrophic lateral sclerosis (ALS) within the mild cognitive impairment (MCI) and mild behavioral impairment (MBI) frameworks. Methods: We used individual task−/item‐level data from the cognitive and behavioral sections of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) from 901 non‐demented ALS to derive neuropsychological sub‐phenotypes pursuant to classical MCI and MBI frameworks and in accordance with an expanded version of Strong's criteria, which also addressed memory and visuo‐spatial measures. Results: The prevalence of MCI and MBI was 39% and 37%, respectively in this retrospective review. The following MCI sub‐phenotypes were identified: dysexecutive MCI—single‐ and multiple‐domain (dMCI‐sd: 63%; dMCI‐md: 24%, respectively); non‐dysexecutive MCI—single‐ and multiple‐domain (ndMCI‐sd: 12%; ndMCI‐md: 1%, respectively). MBI was classified as follows: apathetic MBI—single‐ and multiple‐domain (aMBI‐sd: 40%; aMBI‐md: 20%, respectively); apathetic‐disinihibited/perseverative MBI—multiple domain (ad/pMBI‐md: 21%); disinihibited/perseverative MBI—multiple domain (d/pMBI‐md: 7%); psychotic MBI—single‐ and multiple‐domain (psyMBI‐sd: 2%; psyMBI‐md: 3%, respectively); unclassifiable MBI—multiple domain (uMBI‐md: 1%). 143 (16%) of patients exhibited mild cognitive and behavioral impairment (MCBI). Conclusions: This study delivers a provisional, ECAS‐based classification for the neuropsychological sub‐phenotyping of non‐demented ALS patients, which, with further validation, might be useful for both research and clinical purposes.