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Mechanisms Underlying the Neuropathic/Chronic Pain Development and Maintenance: Focus on...
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Mechanisms Underlying the Neuropathic/Chronic Pain Development and Maintenance: Focus on Pharmacological Targets and Therapeutic Approaches

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Neuropharmacology and Neuropathology".

Deadline for manuscript submissions: 25 May 2026 | Viewed by 7897

Special Issue Editor

Dr. Giada Amodeo

E-Mail Website
Guest Editor
Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Vanvitelli 32, 20129 Milano, Italy
Interests: pain; neuroinflammation; aging; mood disorders
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Pain can result from a wide range of medical conditions, indeed, it is frequently observed in patients with musculoskeletal diseases (e.g., osteoarthritis, rheumatoid arthritis, fibromyalgia, chronic back pain, myofascial pain syndrome, etc.), neurological disorders (peripheral neuropathy of various etiologies, multiple sclerosis, Parkinson’s disease, post-stroke pain, etc.), oncological conditions (related both to the tumour itself and to treatments, such as chemotherapy and radiotherapy), gastrointestinal diseases (e.g., irritable bowel syndrome, chronic inflammatory bowel diseases, chronic pancreatitis, etc.), gynecological/urogenital disorders (e.g., endometriosis, interstitial cystitis, vulvodynia, chronic prostatitis, etc.), and other conditions (e.g., chronic headache and migraine, chronic post-surgical pain, psychogenic pain, etc.).

Chronic pain is not merely a symptom but is recognized as a disease, as it may persist even after the apparent resolution of the initial cause. Recently, the WHO estimated that one in five people worldwide suffer or have suffered from chronic pain. This is a dramatic picture, considering that current treatments are often unsatisfactory or come with significant side effects.

Furthermore, the experience of pain is shaped by emotional and cognitive dimensions, past experiences, psychological structure, and socio-cultural factors. Identifying the mechanisms underlying the development of pain, predictive biomarkers, and novel therapeutic approaches remains an open challenge.

This Special Issue will welcome original clinical and preclinical studies as well as review manuscript.

Dr. Giada Amodeo
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Brain Sciences is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • neuropathic pain
  • chronic pain
  • mood alteration
  • neurons
  • glia cells
  • cytokines
  • neuroinflammation

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Published Papers (3 papers)

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Research

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11 pages, 482 KB  
Article
Radiofrequency Ablation and Pulsed Radiofrequency of Suprascapular Nerves for Managing Chronic Shoulder Pain
by Alaa Abd-Elsayed, Tristan R. Argall, Lukas J. Henjum, Dustin M. McKindsey, Nathan A. Perkins and Kenneth J. Fiala
Brain Sci. 2025, 15(9), 915; https://doi.org/10.3390/brainsci15090915 - 26 Aug 2025
Viewed by 2760
Abstract
Background: Chronic pain is a major contributor to a reduced quality of life in the United States, with chronic shoulder pain comprising a sizeable portion of complaints. Multiple techniques are utilized in the treatment of chronic shoulder pain, but many patients report significant [...] Read more.
Background: Chronic pain is a major contributor to a reduced quality of life in the United States, with chronic shoulder pain comprising a sizeable portion of complaints. Multiple techniques are utilized in the treatment of chronic shoulder pain, but many patients report significant pain refractory to these modalities. For these patients, the suprascapular nerve’s radiofrequency ablation (RFA) offers a potential long-lasting solution. Methods: This retrospective analysis used data from UW Health HealthLink records of patients who received suprascapular RFA from June 2017 to May 2024. Data were collected across 31 procedures, covering demographics, RFA technique, procedure efficacy, duration of relief, adverse events, and relevant medical history. The data were analyzed using a paired t-test. Results: The average pre-RFA pain score was 6.08/10, and the average post-RFA pain score was 2.95/10. The average percentage improvement was 63.3%, with a mean duration of improvement of 3.12 months. Five procedures yielded no improvement in pain. Conclusions: This study demonstrated that RFA is an effective alternative therapy for chronic shoulder pain refractory to conventional pain management strategies, with a potential for long-term relief. Limitations of this study are due to the inherent challenges of retrospective analyses. Full article
(This article belongs to the Special Issue Mechanisms Underlying the Neuropathic/Chronic Pain Development and Maintenance: Focus on Pharmacological Targets and Therapeutic Approaches)
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Review

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27 pages, 3362 KB  
Review
Cell-Free Therapies for Chronic Pain: The Rise of the Mesenchymal Stem Cell Secretome
by Giada Amodeo, Giulia Galimberti, Stefania Niada, Chiara Giannasi, Elena Della Morte, Silvia Franchi, Benedetta Riboldi, Stefania Ceruti, Anna Teresa Brini and Paola Sacerdote
Brain Sci. 2025, 15(12), 1263; https://doi.org/10.3390/brainsci15121263 - 25 Nov 2025
Viewed by 374
Abstract
Chronic pain is a pervasive global health issue that significantly impairs quality of life and remains inadequately managed by current therapeutic options. Traditional pharmacological treatments often offer limited relief and are associated with significant side effects, highlighting the urgent need for safer and [...] Read more.
Chronic pain is a pervasive global health issue that significantly impairs quality of life and remains inadequately managed by current therapeutic options. Traditional pharmacological treatments often offer limited relief and are associated with significant side effects, highlighting the urgent need for safer and more effective alternatives. Among emerging strategies, mesenchymal stem cell (MSC)-derived secretome, an acellular product composed of bioactive molecules such as cytokines, growth factors and extracellular vesicles, has gained increasing attention for its potent anti-inflammatory, neuroprotective and immunomodulatory properties. Unlike whole-cell therapies, secretome-based interventions offer advantages, including lower immunogenicity, higher safety and easier standardization and storage. Preclinical studies demonstrated that MSC secretome effectively alleviates pain-like behavior across various models of neuropathic, inflammatory and degenerative pain, primarily through neuroimmune modulation and glial cell reprogramming. In vitro experiments confirm its role in promoting neuronal survival, regulating opioid receptor expression and modulating (neuro)inflammatory responses. Preliminary clinical evidence supports its analgesic efficacy in conditions such as osteoarthritis, chronic low back pain and post-surgical pain, with a favorable safety profile and promising therapeutic outcomes. However, challenges remain, including variabilities in secretome composition, lack of standardized production protocols and absence of large-scale clinical trials. Despite these limitations, MSC secretome therapy represents a transformative approach in pain medicine. Continued research efforts are essential to optimize formulation, dosing and delivery strategies, as well as to clarify the regulatory landscape. With further validation, the MSC secretome could emerge as a novel, scalable and clinically viable solution for the management of chronic pain, bridging critical gaps in current treatment paradigms. Full article
(This article belongs to the Special Issue Mechanisms Underlying the Neuropathic/Chronic Pain Development and Maintenance: Focus on Pharmacological Targets and Therapeutic Approaches)
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13 pages, 505 KB  
Review
Sphenopalatine Ganglion Blocks in Headache Management: A Review
by Andrei Lyle Bautista, Killian Coyne, Alexander Bautista and Alaa Abd-Elsayed
Brain Sci. 2025, 15(7), 672; https://doi.org/10.3390/brainsci15070672 - 22 Jun 2025
Viewed by 4795
Abstract
Headache disorders are among the most prevalent and disabling neurological conditions worldwide, affecting more than three billion individuals and contributing to a substantial socioeconomic burden. Despite the availability of pharmacologic treatments such as triptans, NSAIDs, and CGRP monoclonal antibodies, a significant proportion of [...] Read more.
Headache disorders are among the most prevalent and disabling neurological conditions worldwide, affecting more than three billion individuals and contributing to a substantial socioeconomic burden. Despite the availability of pharmacologic treatments such as triptans, NSAIDs, and CGRP monoclonal antibodies, a significant proportion of patients remain refractory or intolerant to these therapies. The sphenopalatine ganglion (SPG), a parasympathetic neural structure in the pterygopalatine fossa, is increasingly recognized as a critical node in the pathophysiology of primary headache disorders. SPG blocks—using local anesthetics, neurolytic agents, or electrical neuromodulation—offer a minimally invasive therapeutic approach by disrupting nociceptive transmission and autonomic activation. This narrative review synthesizes the anatomical and physiological rationale for SPG intervention, details various procedural techniques, evaluates clinical evidence across headache subtypes, and explores future research directions. Conditions covered include migraine, cluster headache, tension-type headache, trigeminal neuralgia, and persistent idiopathic facial pain. With expanding evidence and evolving technologies, SPG-targeted interventions have the potential to reshape the management of refractory headaches and facial pain syndromes. Full article
(This article belongs to the Special Issue Mechanisms Underlying the Neuropathic/Chronic Pain Development and Maintenance: Focus on Pharmacological Targets and Therapeutic Approaches)
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