Accepted

Fibromyalgia is a chronic pain condition characterized by generalized musculoskeletal pain, hyperalgesia and allodynia, commonly associated with other symptoms such as fatigue, poor sleep quality, anxiety and depression. The clinical manifestations of this rheumatic disease have significant psychosocial and economic repercussions, with a substantial impact on health status, quality of life and social activities. Currently, recommendations for the management of fibromyalgia include patient education and non-pharmacological interventions, and among the indicated treatments, clinical guidelines include several physiotherapeutic resources, essential for individuals affected by this syndrome. Research in the physiotherapy field has demonstrated its effectiveness, but there is a need to update the literature. This study aims to identify the effectiveness of physiotherapy in the treatment of individuals with fibromyalgia. We performed a literature review looking for articles dated from March 2012 to March 2022 using the terms "fibromyalgia", "physiotherapy", "physical therapy", "rehabilitation" in different languages in various databases and their main information was read and collected and presented in a descriptive way. The effects of physiotherapy interventions are summarized in order to provide a reference for future research and clinical application. Research on non-pharmacological physiotherapy-oriented treatments has grown in recent years as an alternative for fibromyalgia treatment. This review allows fibromyalgia patients to receive appropriate physical therapy interventions to promote their health.

Pain treatment services and clinical indicators of pain chronicity focus on afferent nociceptive projections and psychological markers of pain perception with little focus on motor processes. Research supports a strong role for the motor system both in terms of pain related disability and in descending pain modulation. However, there is little understanding of the neurological regions implicated in pain-motor interactions and how the motor and sensory systems interact under conditions of pain. We performed an ALE meta-analysis on two clinical cohorts with atypical sensory and motor processes under conditions of pain and no pain. Persons with sensory altered processing (SAP) and no pain presented with greater activity in the precentral and supplementary motor area relative to persons with self-reported pain. In persons with motor altered processing (MAP), there appeared to be a suppression of activity in key pain regions such as the insula, thalamus, and postcentral gyrus. As such, activation within the motor system may play a critical role in dampening pain symptoms in persons with SAP, and in suppressing activity in key pain regions of the brain in persons with MAP. Future research endeavors should focus on understanding how sensory and motor processes interact both to understand disability and discover new treatment avenues.

Visual snow syndrome is a neurological condition characterized by continuous visual disturbance and a range of non-visual symptoms, including tinnitus and migraine. Little is known about the pathological mechanisms underlying visual snow syndrome. Here, we assessed brain morphometry and microstructure in visual snow syndrome patients using high-resolution structural and quantitative MRI. Forty visual snow syndrome patients (22 with migraine) and 43 controls underwent 7-Tesla MRI (MP2RAGE, 0.75 mm isotropic resolution). Volumetric and quantitative T1 values were extracted for white and grey matter regions and compared between groups. Where regions were significantly different between groups (false discovery rate corrected for multiple comparisons), comparisons were examined between patients with and without migraine. For visual snow syndrome patients, significant MRI variables were correlated with clinical severity (number of visual symptoms, perceived visual snow intensity, disruptiveness, fatigue and quality of life) and psychiatric symptoms prevalent in visual snow syndrome (depression, anxiety and depersonalization). Finally, cortical regions and individual thalamic nuclei were studied. Compared with controls, visual snow syndrome patients demonstrated a trend towards larger brain and white matter volumes and significantly lower T1 values for the entire cortex ( < 0.001), thalamus ( = 0.001) and pallidum ( = 0.001). For the patient group, thalamic T1 correlated with number of visual symptoms ( = 0.019,  = 0.390) and perceived disruptiveness of visual snow ( = 0.010,  = 0.424). These correlations did not survive multiple comparison corrections. As for specificity in visual snow syndrome group, T1 changes were most evident in caudal regions (occipital cortices) followed by parietal, temporal and prefrontal cortices. T1 values differed between groups for most individual thalamic nuclei. No differences were revealed between patients with and without migraine. In visual snow syndrome patients, we observed no changes in morphometry, instead widespread changes in grey matter microstructure, which followed a caudal-rostral pattern and affected the occipital cortices most profoundly. Migraine did not appear to independently affect these changes. Lower T1 values may potentially result from higher neurite density, myelination or increased iron levels in the visual snow syndrome brain. Further investigation of these changes may enhance our understanding of the pathogenesis of visual snow syndrome, ultimately leading to new treatment strategies.

Waste removal is essential for maintaining homeostasis and the normal function of the central nervous system (CNS). The glymphatic system based on aquaporin-4 (AQP4) water channels on the endfeet of astrocytes is recently discovered as the excretion pathway for metabolic waste products of CNS. In the CNS, α-syntrophin (SNTA1) directly or indirectly anchors AQP4 in astrocyte membranes facing blood vessels. Studies have indicated that β-hydroxybutyrate (BHB) can raise the expression of SNTA1 and thus restoring AQP4 polarity in mice models with Alzheimer's disease. The study aims to evaluate the neuroprotective mechanism of BHB in rats with painful diabetic neuropathy (PDN). PDN rats were modeled under a high-fat and high-glucose diet with a low dose of streptozotocin. Magnetic resonance imaging (MRI) was applied to observe the clearance of contrast to indicate the functional variability of the spinal glymphatic system. Mechanical allodynia was assessed by paw withdrawal threshold. The expressions of SNTA1 and AQP4 were tested, and the polarity reversal of AQP4 protein was measured. As demonstrated, PDN rats were manifested with deceased contrast clearance of the spinal glymphatic system, enhanced mechanical allodynia, lower expression of SNTA1, higher expression of AQP4, and reversed polarity of AQP4 protein. An opposite change in the above characteristics was observed in rats being treated with BHB. This is the first study that demonstrated the neuroprotective mechanism of BHB to attenuate PDN restoration of the AQP4 polarity in the spinal glymphatic system and provides a promising therapeutic strategy for PDN.

The role of GABAergic cell transplantation in improving neuropathic pain is controversial. We comprehensively searched the relevant literature to identify animal studies of GABAergic cell transplantation that recorded pain behaviors as an outcome according to the Cochrane Handbook 5.0.2. Controlled studies assessing the administration of GABAergic neurons or GABAergic neuronal progenitor cells to rat or mouse neuropathic pain animal models were included. Basic design information and mechanical allodynia thresholds and heat hyperalgesia thresholds data were collected. The risk of bias for the animal experiments was assessed according to the SYRCLE's tool. This study included 10 full-text articles. GABAergic cells transplantation leads to a statistically significant improvement of allodynia (SMD = 5.26; 95% confidence interval: 3.02-7.51; < 0.001) and hyperalgesia (SMD: 4.10; 95% confidence interval: 1.84-6.35; < 0.001). Differentiated GABAergic cells and without antibiotics using may have a better effect for improving neuropathic pain. GABAergic cell transplantation is a promising treatment for improving neuropathic pain. This systematic review and meta-analysis evaluated the effects of GABAergic cell transplantation on neuropathic pain, which can guide future clinical trials and possible clinical treatments, and better attenuate neuropathic pain caused by abnormal circuit hyperexcitability.