Rejected

Leukocyte infiltration and persistence within peripheral nerves have been implicated in chronic nociception pathogenesis in murine peripheral neuropathy models. Endoneurial cytokine and chemokine expression contribute to leukocyte infiltration and maintenance of a pro-inflammatory state that delays peripheral nerve recovery and promotes chronic pain behaviors in these mice. However, there has been a failure to translate murine model data into safe and effective treatments for chronic neuropathic pain in peripheral neuropathy patients, or develop reliable biomarkers that may help diagnose or determine treatment responses in affected patients. Initial work showed that persistent sciatic nerve CD11b+ CD45+ leukocyte infiltration was associated with disease severity in three mouse models of inflammatory and traumatic peripheral neuropathies, implying a direct contributing role in disease pathogenesis. In support of this, CD11b+ leukocytes were also seen in the sural nerve biopsies of chronic neuropathic pain patients with three different peripheral neuropathies. Systemic CD11b antagonism using a validated function-neutralizing monoclonal antibody effectively treated chronic nociception following unilateral sciatic nerve crush injury (a representative traumatic neuropathy model associated with axonal degeneration and increased blood-nerve barrier permeability) and does not cause drug addiction behaviors in adult mice. These data suggest that CD11b could be an effective molecular target for chronic neuropathic pain treatment in inflammatory and traumatic peripheral neuropathies. Despite known murine peripheral neuropathy model limitations, our initial work suggests that early expression of pro-inflammatory cytokines, such as tissue inhibitor of metalloproteinases-1 may predict subsequent chronic nociception development following unilateral sciatic nerve crush injury. Studies aligning animal model investigation with observational data from well-characterized human peripheral neuropathies, including transcriptomics and proteomics, as well as animal model studies using a human clinical trial design should foster the identification of clinically relevant biomarkers and effective targeted treatments with limited addiction potential for chronic neuropathic pain in peripheral neuropathy patients.

Chronic pain affects almost 38% of the Portuguese adult population, with high costs for both patients and society. Those who suffer with chronic pain frequently complain of feeling misunderstood and of lack of support. These complaints are the main reason why support telephone lines for chronic pain were created in some countries. However, there is no scientific data supporting their creation or evaluating their performance. This paper presents a qualitative study protocol to assess patients and healthcare professionals' perspectives on the creation of a telephone support line for chronic pain. It constitutes the first step to attain the main goal of developing and implementing a functioning support line for chronic pain in Portugal. The methodology to assess patients and healthcare professionals' perspectives and needs is presented. In order to gather information as close to reality as possible, focus groups interviews were chosen as data sources. Given the present context of the COVID-19 pandemic, meetings will take place online, using a digital platform. All interviews will be transcribed verbatim, coded and synthesised into categories and main themes. Thematic analysis will be conducted using NVivo® V12 software, employing an iterative and reflexive approach. Finally, comparative and relational analysis will be performed in order to identify topics where patients and professionals converge or greatly diverge. The findings will be useful for grounding the creation of a telephone support line for chronic pain patients. Results dissemination will be important for policy-makers to develop a new perspective towards chronic pain services available.

Fibro-adipose vascular anomaly (FAVA) is a recently described complex and painful benign lesion found in young adults and the pediatric population composed of intramuscular vascular, fibrous, and adipose tissues. A previous report has identified the presence of somatic mosaic mutations in the gene for the catalytic subunit of phosphatidylinositol 3-kinase () in cases of FAVA. Herein, we present a case of FAVA found in a 23-year-old male patient who presented with chronic wrist pain associated with a mass, and we identified an associated somatic activating mutation (H1047R) in . We briefly review the relevant literature surrounding the identification and histology of FAVA, the known mutational spectrum, downstream signaling pathways, and relevant treatment modalities. Our case highlights the association between FAVA and somatic mosaic activating mutations.

Identifying the prevalence of neuropathic pain components in patients with chronic tendinopathy conditions using the Self-Administered Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) questionnaire.

To evaluate the usefulness of surgical neurolysis for neuropathic pain relief in patients with posttraumatic brachial plexus injury (BPI).

The extent, range, and nature of available research in the field of herbal therapies for osteoarthritis (OA) have not been systematically analyzed. This study aimed to map the literature available on herbal therapies for OA and identify global hotspots and trends in this field.

Total Knee Arthroplasty (TKA) is an increasingly common procedure performed for advanced osteoarthritis. Optimal perioperative pain management strategies are critical for early mobilization and shorter hospital stays in TKA. Peripheral nerve blocks commonly used in TKA perioperative analgesia including individual and combined femoral, obturator, sciatic, lumbar plexus, and adductor canal nerve blocks. Overall, the safety profile varies depending on which block is utilized, but the current evidence suggests when optimally chosen and delivered, peripheral nerve blocks may provide a safe, effective option for perioperative analgesia. Determining optimal analgesic regimens for total knee arthroplasty is critical to improve postoperative pain, patient satisfaction, decreasing opioid usage, recovery times and functional outcomes, and as such, peripheral nerve blocks may represent a viable option to supplement analgesic requirements in the perioperative period.

This article was designed to provide critical evidence into the relationship between ambient temperature and intensity of back pain in people with lumbar disc herniation (LDH).

Paravertebral block (PVB) has been widely used in postoperative analgesia, especially in thoracic and breast surgery. However, the efficacy and safety of PVB for analgesia after renal surgery remains uncertain. Therefore, this study aimed to determine the postoperative analgesic efficacy and safety of PVB in renal surgery.

As the COVID-19 pandemic continues to unfold, numerous neurological symptoms emerge. The literature reports more and more manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) related to headache, dizziness, impaired consciousness, cognitive impairment, and motor disorders. Moreover, the infection of SARS-CoV-2 may have a durable neurological impact. ACE2/TMPRSS2 is the main entry point into cells for some strains of coronaviruses (CoVs), including SARS-CoV-2, which uses it to target the central nervous system (CNS). The aim of this study was to characterize the scope of the potential complex impact of a SARS-CoV-2 infection in the brain. It concerns different scales: the topographic, cognitive, sensorimotor, and genetic one. We investigated which cognitive and sensorimotor functions are associated with the brain regions where ACE2/TMPRSS2 is overexpressed, hypothesising that they might be particularly affected by the infection. Furthermore, overexpressed genes in these regions are likely to be impacted by COVID-19. This general understanding is crucial to establish the potential neurological manifestations of the infection. Data on mRNA expression levels of genes were provided by the Allen Institute for Brain Science (AIBS), and the localisation of brain functions by the LinkRbrain platform. The latter was also used to analyze the spatial overlap between ACE2/TMPRSS2 overexpression, and either function-specific brain activations or regional overexpression of other genes. The characterisation of these overexpressed genes was based on the GeneCards platform and the gene GSE164332 from the Gene Expression Omnibus database. We analysed the cognitive and sensorimotor functions whose role might be impaired, of which 88 have been categorised into seven groups: memory and recollection, motor function, pain, lucidity, emotion, sensory, and reward. Furthermore, we categorised the genes showing a significant increase in concentration of their mRNAs in the same regions where ACE2/TMPRSS2 mRNA levels are the highest. Eleven groups emerged from a bibliographical research: neurodegenerative disease, immunity, inflammation, olfactory receptor, cancer/apoptosis, executive function, senses, ischemia, motor function, myelination, and dependence. The results of this exploration could be in relation to the neurological symptoms of COVID-19. Furthermore, some genes from peripheral blood are already considered as biomarker of COVID-19. This method could generate new hypotheses to explore the neurological manifestations of COVID-19.