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Life
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Pain and Therapy: Historical Perspectives and Future Directions
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Pain and Therapy: Historical Perspectives and Future Directions

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Medical Research".

Deadline for manuscript submissions: closed (22 May 2025) | Viewed by 3616

Special Issue Editors

Prof. Dr. Francesco Scaglione

E-Mail Website
Guest Editor
Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy
Interests: clinical pharmacology; infectious diseases; antimicrobial agents; oncology and onco-hematology
Special Issues, Collections and Topics in MDPI journals
Dr. Arianna Pani

E-Mail Website
Guest Editor
Toxicology Department of Oncology and Hemato-Oncology, University of Milan, Via Vanvitelli, 20133 Milan, Italy
Interests: cancer; antibiotic; treatement
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The Special Issue will collect original research articles, reviews, systematic reviews, and meta-analyses on physiological and therapeutic aspects of pain. Papers on innovative aspects and on the various types of pain, i.e., nociceptive, neuropathic, and nociplastic, are welcome. We would like to give particular emphasis to therapies with critical insights on opioids, NSAIDs, and supportive therapies. Finally, nutraceutical remedies of pain are welcome.

Prof. Dr. Francesco Scaglione
Dr. Arianna Pani
Guest Editors

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. Life 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

  • pain
  • nociceptive pain
  • neuropathic pain
  • neoplastic pain
  • pain physiology
  • pain treatment

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Published Papers (4 papers)

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Research

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18 pages, 2862 KiB  
Article
Effects of Repetitive Transcranial Magnetic Stimulation Applied over the Primary Motor Cortex on the Offset Analgesia Phenomenon
by Elisa Antoniazzi, Camilla Cavigioli, Vanessa Tang, Clara Zoccola, Massimiliano Todisco, Cristina Tassorelli and Giuseppe Cosentino
Life 2025, 15(2), 182; https://doi.org/10.3390/life15020182 - 26 Jan 2025
Viewed by 741
Abstract
In this study, we investigate the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) applied over the left upper limb primary motor cortex (M1) on the offset analgesia (OA) phenomenon, a measure of endogenous pain modulation. In particular, we aim to determine whether [...] Read more.
In this study, we investigate the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) applied over the left upper limb primary motor cortex (M1) on the offset analgesia (OA) phenomenon, a measure of endogenous pain modulation. In particular, we aim to determine whether rTMS influences OA differently in the forearm region, corresponding to the stimulated cortical area, compared to the trigeminal region. Twenty-two healthy volunteers underwent three experimental sessions: a baseline session without stimulation, an active rTMS session, and a sham rTMS session. Quantitative sensory testing (QST) paradigms, including warm and cold detection thresholds, heat pain threshold corresponding to a visual analogue scale (VAS) score of approximately 50–60 out of 100 (Pain50–60), and constant and offset trials, were assessed in both the forearm and trigeminal regions. The results revealed that active rTMS significantly enhanced the OA phenomenon in the forearm during the late phase, while no significant effects were observed in the trigeminal region. These findings suggest that rTMS may modulate central pain mechanisms in a body region-specific manner, potentially linked to the somatotopic organization of M1. This study points to possible mechanisms of action of rTMS for pain relief, highlighting the importance of region-specific effects in chronic pain treatment. Further research is needed to investigate the underlying mechanisms and clinical applicability of rTMS in patients with chronic pain conditions, especially when OA is compromised. Full article
(This article belongs to the Special Issue Pain and Therapy: Historical Perspectives and Future Directions)
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Review

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12 pages, 1045 KiB  
Review
Ketoprofen Lysine Salt vs. Ketoprofen Acid: Assessing the Evidence for Enhanced Safety and Efficacy
by Agnese Graziosi, Michele Senatore, Gianluca Gazzaniga, Stefano Agliardi, Arianna Pani and Francesco Scaglione
Life 2025, 15(4), 659; https://doi.org/10.3390/life15040659 - 16 Apr 2025
Cited by 1 | Viewed by 514
Abstract
Endoscopic investigations reveal that a significant majority of individuals taking NSAIDs exhibit acute hemorrhages and mucosal erosions within the gastroduodenal lining. Ketoprofen acid (KA) is a potent NSAID with established efficacy and cardiovascular tolerability, but its gastric tolerability is a recognized limitation. To [...] Read more.
Endoscopic investigations reveal that a significant majority of individuals taking NSAIDs exhibit acute hemorrhages and mucosal erosions within the gastroduodenal lining. Ketoprofen acid (KA) is a potent NSAID with established efficacy and cardiovascular tolerability, but its gastric tolerability is a recognized limitation. To mitigate this, ketoprofen lysine salt (KLS) was developed. This review evaluates the pharmacological advantages of KLS over KA. While both KA and KLS maintain similar potency, KLS offers distinct advantages. Firstly, KLS demonstrates superior gastrointestinal protection through enhanced antioxidant properties and upregulation of mucosal defenses, as evidenced by both in vitro and in vivo studies. Secondly, KLS exhibits significantly faster absorption, leading to a more rapid onset of analgesic effects; this is attributed to its increased solubility and faster achievement of therapeutic concentrations. In essence, KLS addresses the gastric tolerability issues of KA while providing a quicker onset of action, making it a valuable alternative for patients requiring NSAID therapy, particularly those with gastric sensitivities or in need of rapid pain relief. Full article
(This article belongs to the Special Issue Pain and Therapy: Historical Perspectives and Future Directions)
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Other

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15 pages, 2932 KiB  
Systematic Review
Prevalence of Neuropathic Pain in Morocco: A Systematic Review and Meta-Analysis
by Zhor Zeghari, Jihane Belayachi, Redouan El Ouardi and Redouane Abouqal
Life 2025, 15(5), 780; https://doi.org/10.3390/life15050780 - 14 May 2025
Viewed by 242
Abstract
This study aims to assess the prevalence of neuropathic pain in the Moroccan population through a systematic review and meta-analysis using a generalized linear mixed model (GLMM). The PRISMA guidelines for systematic reviews and meta-analysis were followed. All observational prevalence studies, conducted in [...] Read more.
This study aims to assess the prevalence of neuropathic pain in the Moroccan population through a systematic review and meta-analysis using a generalized linear mixed model (GLMM). The PRISMA guidelines for systematic reviews and meta-analysis were followed. All observational prevalence studies, conducted in both the general population and hospital settings in Morocco, published before 1 December 2023, were included, provided that neuropathic pain was identified based on consensus criteria. The databases searched included PubMed, Scopus, Web of Science, and the gray literature (Google Scholar). Data on the sample size, subgroups, sociodemographic and clinical characteristics of participants, as well as the methodology of each study, were extracted. The Joanna Briggs Institute tool for prevalence studies was used to assess the risk of bias. A random-effects generalized linear mixed model was applied for direct data adjustment, using Knapp–Hartung standard error correction. Heterogeneity was explored using Cochran’s Q test, Higgins’ I2 statistic, and prediction intervals. Subgroup analysis was performed based on underlying pathology, while meta-regression was conducted according to age and sex ratio. Publication bias was assessed using the Doi plot and LFK test. Sensitivity analysis was performed by stratifying studies based on their risk of bias. The statistical analysis was conducted using R software version 4.3.1 with the meta, metafor, metasens, and robvis packages. A total of 33 publications were identified, of which 17 studies were retained after removing duplicates and applying the eligibility criteria. These studies were published between 2013 and 2023 and included either the general population (one study) or patients with diabetes (seven), obesity (one), rheumatologic conditions (six), Parkinson’s disease (one), or cancer (one). The DN4 score was the most commonly used tool to diagnose neuropathic pain. The risk of bias was rated as low in two studies, moderate in eight, and high in seven. The pooled overall prevalence was 22% (95% CI [14.8; 31.5]) with an I2 of 98% (p < 0.01). In subgroup analyses, the prevalence was 19.9% among rheumatology patients, 10.2% in oncology patients, 9.4% in Parkinson’s patients, 26.6% in diabetics, 58.6% in obese individuals, and 10.6% in the general population. Meta-regression by sex indicated significantly lower prevalence in men, and prevalence increased with age but did not reach statistical significance. After stratification based on the risk of bias, the pooled prevalence was 15.4% for the two studies with a low risk of bias. The overall prevalence of neuropathic pain in Morocco is relatively high at 22%, with significant variability across medical specialties. However, this prevalence is likely overestimated. Stronger and higher-quality studies are needed to obtain more accurate estimates. Full article
(This article belongs to the Special Issue Pain and Therapy: Historical Perspectives and Future Directions)
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12 pages, 2367 KiB  
Case Report
Trigeminal Neuralgia Treatment via Piezosurgical Enlargement of the Mental Foramen
by Radosław Jadach and Karolina Osypko
Life 2025, 15(3), 382; https://doi.org/10.3390/life15030382 - 28 Feb 2025
Viewed by 1658
Abstract
Background: This article and the novel surgical approach described here were inspired by the ideas and observations of the late professors T. Pawela and J. Wnukiewicz. The authors present the medical history and unique surgical treatment of four patients with trigeminal neuralgia, who, [...] Read more.
Background: This article and the novel surgical approach described here were inspired by the ideas and observations of the late professors T. Pawela and J. Wnukiewicz. The authors present the medical history and unique surgical treatment of four patients with trigeminal neuralgia, who, despite pharmacological treatment and numerous specialists being involved in the treatment process, continued suffering. Our belief is that the direct cause of the symptoms is a narrow mental foramen, which compresses the mental nerve. It can be easily verified by local anesthesia administration to verify the trigger point, and by analyzing CBCT scans with a special emphasis on the diameter of both mental foramina. Methods: Surgical decompression by narrow mental foramen enlargement was conducted with a piezosurgical device. In this procedure, a rectangle of cortical bone is gently and precisely cut around the mental foramen and then into smaller pieces. This technique enables its easy and safe removal. Then, the mental nerve is left loose, uncompressed. Results: All four patients reported immediate recovery, their pain attacks stopped, and their quality of life improved significantly. One patient reported temporal hypoesthesia that lasted 5 months post-op. About 2 years post-op, another patient reported rare recurrences of pain, although much less severe than before surgery. Conclusions: This type of treatment may be considered when trigeminal neuralgia cannot be classified as classic or as secondary and is unresponsive to pharmacological treatment. A piezosurgical device seems to be the safest option in terms of potential damage to the nerve. Further research should include a larger sample of patients and focus on analyzing the mental foramina diameter of patients with idiopathic trigeminal neuralgia. Full article
(This article belongs to the Special Issue Pain and Therapy: Historical Perspectives and Future Directions)
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