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Biomedicines
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Mechanisms and Pharmacological Targets for Pain
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Mechanisms and Pharmacological Targets for Pain

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 31 October 2025 | Viewed by 4831

Special Issue Editor

Dr. Renan F. do Espírito-Santo

E-Mail Website
Guest Editor
Department of Neural and Pain Sciences, University of Maryland School of Dentistry, Baltimore, MD, USA
Interests: pain; inflammation; pharmacology; drug discovery

Special Issue Information

Dear Colleagues,

This Special Issue, entitled "Mechanisms and Pharmacological Targets for Pain", aims to delve into the complex biological and molecular underpinnings of pain, a pervasive and often debilitating symptom affecting millions worldwide. This Special Issue will cover the diverse mechanisms involved in pain perception and transmission, from peripheral nociceptor activation to central nervous system processing. It will explore the latest research on inflammatory, neuropathic, and chronic pain conditions, highlighting the role of various cellular and molecular players such as ion channels, neurotransmitters, and cytokines. Additionally, this Special Issue will focus on identifying and evaluating novel pharmacological targets for pain management. It will include studies on new analgesic drugs, advancements in targeted therapies, and innovative delivery systems aimed at enhancing efficacy and reducing side effects. This Special Issue will also address the challenges and opportunities of translating preclinical findings into clinical practice. By bringing together cutting-edge research and expert insights, this Special Issue seeks to advance our understanding of pain mechanisms and foster the development of more effective and safer pain treatments.

Dr. Renan F. do Espírito-Santo
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 100 words) can be sent to the Editorial Office for announcement on this website.

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. Biomedicines 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 2600 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

  • drug discovery
  • chronic pain
  • inflammatory pain
  • mechanisms of action
  • pain pharmacology
  • immunomodulation
  • neuropathic pain

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Published Papers (4 papers)

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Research

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16 pages, 4129 KiB  
Article
Effective Management of Chronic Low Back Pain in the Elderly: A One-Year Cohort Study of Oxygen–Ozone Therapy Under CT Guidance Combined with Alpha Lipoic Acid, Palmitoylethanolamide, and Myrrh
by Matteo Bonetti, Michele Frigerio, Gian Maria Ottaviani, Giannantonio Pellicanò, Alessio Zambello, Mario Muto, Francesco Carinci and Federico Maffezzoni
Biomedicines 2025, 13(5), 1250; https://doi.org/10.3390/biomedicines13051250 - 20 May 2025
Viewed by 94
Abstract
Background and Objective: This observational study aimed to evaluate the clinical efficacy of combined oxygen–ozone (O2-O3) therapy under CT guidance with the oral administration of alpha-lipoic acid (ALA), palmitoylethanolamine (PEA), and myrrh in elderly patients suffering from chronic low [...] Read more.
Background and Objective: This observational study aimed to evaluate the clinical efficacy of combined oxygen–ozone (O2-O3) therapy under CT guidance with the oral administration of alpha-lipoic acid (ALA), palmitoylethanolamine (PEA), and myrrh in elderly patients suffering from chronic low back pain (LBP). Given the rising prevalence of degenerative spinal diseases in older adults, this study addresses the need for effective, minimally invasive treatment options. Methods: A total of 276 patients aged 65 to 92 years, with chronic unilateral or bilateral LBP, underwent CT-guided paravertebral infiltrations with an O2-O3 gas mixture. This treatment was complemented with a 30-day regimen of ALA (800 mg/day), PEA (600 mg/day), and myrrh (200 mg/day). Clinical outcomes were assessed at one month and one year post-treatment using the Visual Analog Scale (VAS) and the modified McNab method. Results: At one month, 32.94% of patients reported an excellent improvement, with the mean VAS score dropping from 8.17 to 2.81. At the one-year follow-up, 68.15% cumulatively experienced positive outcomes, with 17.78% reporting the complete resolution of pain. In this occasion, the mean VAS score was 3.57. Conclusions: The study demonstrates that the combination of oxygen–ozone therapy and oral ALA, PEA, and myrrh is a promising alternative for managing chronic low back pain in the elderly, leading to significant pain reduction and improved quality of life. Findings emphasize the need for further research to validate these results and explore the long-term benefits. Full article
(This article belongs to the Special Issue Mechanisms and Pharmacological Targets for Pain)
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13 pages, 2068 KiB  
Article
Acetyl-L-Carnitine as an Add-On Treatment in Fibromyalgia Syndrome: A Retrospective Analysis on 183 Patients, According to the Generalized Linear Mixed Model for Longitudinal Data
by Vittorio Schweiger, Libera Villagrossi, Francesco Taus, Leonardo Gottin, Eleonora Bonora, Marco Anderloni, Giustino Varrassi, Luca Polati, Marta Nizzero, Alvise Martini and Enrico Polati
Biomedicines 2025, 13(4), 820; https://doi.org/10.3390/biomedicines13040820 - 28 Mar 2025
Viewed by 653
Abstract
Background. Fibromyalgia Syndrome (FMS) is characterized by chronic widespread pain, sleep disturbances, fatigue and cognitive impairment. Methods. In this retrospective study, we analyzed data collected between 2017 and 2022 regarding Acetyl-L-Carnitine (ALC) as an add-on treatment in 183 adult patients with [...] Read more.
Background. Fibromyalgia Syndrome (FMS) is characterized by chronic widespread pain, sleep disturbances, fatigue and cognitive impairment. Methods. In this retrospective study, we analyzed data collected between 2017 and 2022 regarding Acetyl-L-Carnitine (ALC) as an add-on treatment in 183 adult patients with FMS according to the 2016 ACR (American College of Rheumatology) criteria and patients’ pain lasting for over three months. Patients with prior exposure to ALC or without informed consent were excluded. Results. Regarding efficacy, in the 137 analyzed patients, the change from baseline to the end of observation in Visual Analogue Scale score (VAS) was statistically significant, ranging from 75.9 ± 1.56 to 51.9 ± 1.99 (p < 0.001). Patients without FMS concomitant drug treatments achieved better VAS reduction than patients who were not drug-free at baseline. Regarding quality of life, a significant improvement in the Revised Fibromyalgia Impact Questionnaire (FIQ-R) score was evidenced, ranging from 75.1 ± 1.13 to 53.5 ± 1.34 (p < 0.001). The Short Form 12 Health Survey (SF12) scores showed a statistically significant improvement in both physical and mental components. Finally, the Pittsburgh Sleep Quality Index (PSQI) did not show a statistically significant difference from baseline. In the whole population, 23 patients (16.7%) reported Adverse Events (AEs), predominantly insomnia, shivering, headaches, and nausea. Only six patients reporting AEs discontinued the ALC treatment. Conclusions. This retrospective study evidenced the efficacy and safety of ALC in FMS patients. This may represent a useful approach, particularly for long-term treatments. Methodologically stronger studies will be necessary to validate our observations. Full article
(This article belongs to the Special Issue Mechanisms and Pharmacological Targets for Pain)
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Review

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18 pages, 592 KiB  
Review
Closed-Loop Spinal Cord Stimulation in Chronic Pain Management: Mechanisms, Clinical Evidence, and Emerging Perspectives
by Nicholas Mangano, Andrew Torpey, Catherine Devitt, George A. Wen, Christopher Doh and Abhishek Gupta
Biomedicines 2025, 13(5), 1091; https://doi.org/10.3390/biomedicines13051091 - 30 Apr 2025
Viewed by 436
Abstract
Background: Chronic pain remains a major clinical challenge, which is often resistant to conventional treatments. Spinal cord stimulation has been used for decades to manage refractory pain, traditionally relying on open-loop systems with fixed-output stimulation. However, these systems fail to account for physiological [...] Read more.
Background: Chronic pain remains a major clinical challenge, which is often resistant to conventional treatments. Spinal cord stimulation has been used for decades to manage refractory pain, traditionally relying on open-loop systems with fixed-output stimulation. However, these systems fail to account for physiological variability, leading to inconsistent pain relief. Closed-loop spinal cord stimulation represents a significant advancement by utilizing evoked compound action potentials to continuously modulate stimulation intensity in real-time, ensuring more stable and effective pain management. Methods: A comprehensive literature review was conducted using PubMed and ClinicalTrials.gov to identify and synthesize relevant published and ongoing studies with a focus on open-loop spinal cord stimulation for managing lower back pain. Results: Clinical trials, including the Avalon and Evoke studies, have demonstrated that closed-loop spinal cord stimulation provides superior pain relief, functional improvement, and reduced opioid dependence compared to traditional open-loop systems. Patients receiving closed-loop stimulation reported significantly higher rates of sustained pain reduction, improved quality of life, and fewer complications related to overstimulation. Emerging studies suggest its potential for conditions beyond back pain, such as neuropathic pain, cancer-related pain, and Raynaud’s phenomenon. Furthermore, cost-effectiveness analyses indicate that closed-loop spinal cord stimulation is a more economically viable treatment option compared to conventional medical management and open-loop systems. Conclusions: Closed-loop spinal cord stimulation represents a transformative development in neuromodulation, offering personalized and adaptive pain management that is distinct from open-loop spinal cord stimulation. Further research is warranted to explore its long-term durability, broader applications, and integration with emerging technologies in pain management. Full article
(This article belongs to the Special Issue Mechanisms and Pharmacological Targets for Pain)
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14 pages, 300 KiB  
Review
Post-Traumatic Trigeminal Neuropathic Pain: A Narrative Review of Understanding, Management, and Prognosis
by Hyun-Jeong Park, Jong-Mo Ahn and Ji-Won Ryu
Biomedicines 2024, 12(9), 2058; https://doi.org/10.3390/biomedicines12092058 - 10 Sep 2024
Cited by 1 | Viewed by 2881
Abstract
This study provides an updated overview of the clinical characteristics of post-traumatic trigeminal neuropathic pain (PTNP) resulting from dental procedures or facial trauma, addressing its etiology, prevalence, evaluation, management, and prognosis. PTNP arises from injury to the trigeminal nerve, which governs sensory and [...] Read more.
This study provides an updated overview of the clinical characteristics of post-traumatic trigeminal neuropathic pain (PTNP) resulting from dental procedures or facial trauma, addressing its etiology, prevalence, evaluation, management, and prognosis. PTNP arises from injury to the trigeminal nerve, which governs sensory and motor functions in the maxillofacial region. The prevalence and characteristics of PTNP vary considerably across studies, with a reported prevalence ranging from 1.55% to 13%. The predominant causative factors are dental procedures, particularly third molar removal and implant placement. While gender distribution varies, a trend towards higher incidence in females is observed, particularly within the 40–60-year age group. Anatomically, the mandibular nerve is frequently involved. PTNP presents with a spectrum of symptoms ranging from tingling sensations to severe pain. Diagnostic challenges arise due to the lack of standardized criteria and potential overlap with focal neuralgia, necessitating comprehensive evaluation. Misdiagnosis can lead to prolonged patient suffering and unnecessary interventions. Successful management hinges on prompt diagnosis and interdisciplinary collaboration, with early intervention crucial in mitigating progression to chronic pain. Although nerve recovery post-trauma is challenging, preventive measures through accurate evaluation and treatment are paramount. Management strategies for PTNP include non-invasive and surgical interventions, with non-invasive approaches encompassing systemic and local pharmacological management. This narrative review aims to enhance uniformity in PTNP evaluation and treatment approaches, ultimately improving patient care and outcomes. Full article
(This article belongs to the Special Issue Mechanisms and Pharmacological Targets for Pain)
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