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Pain: From Molecular Basis to Therapy
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Pain: From Molecular Basis to Therapy

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (28 February 2025) | Viewed by 1131

Special Issue Editor

Dr. Samuel J. Lin

E-Mail Website
Guest Editor
Division of Plastic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
Interests: biomaterial‒host interactions; silk; biofilms; bacteria‒host interaction; chronic inflammation; rejection
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Pain is a multifaceted and pervasive phenomenon that significantly impacts the quality of life of millions worldwide. Despite considerable advancements in our understanding of its mechanisms, effective management of pain remains a major clinical challenge. Pain can arise from various conditions, including inflammation, nerve damage, and chronic diseases, each involving complex molecular and cellular processes. Advances in molecular biology have provided deeper insights into the pathways and mediators involved in pain signaling, opening new avenues for targeted therapeutic interventions.

This Special Issue, “Pain: From Molecular Basis to Therapy”, aims to present cutting-edge research and comprehensive reviews that delve into the molecular underpinnings of pain. Topics of interest include the identification and characterization of pain-related receptors and ion channels, the role of neurotransmitters and neuromodulators in pain pathways, genetic and epigenetic influences on pain sensitivity, and the interaction between immune cells and neurons in pain. Additionally, we seek contributions that explore innovative therapeutic strategies, including novel pharmacological agents, gene therapy, and non-pharmacological approaches such as neuromodulation and regenerative medicine.

We invite researchers and clinicians to submit original research articles, reviews, and short communications that advance our understanding of the molecular basis of pain and propose novel therapeutic approaches. Through this Special Issue, we aim to foster a comprehensive understanding of pain mechanisms and facilitate the development of more effective pain management strategies.

Dr. Samuel J. Lin
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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 mechanisms
  • molecular signaling
  • neurotransmitters
  • ion channels
  • genetic predisposition
  • epigenetic regulation
  • immune–neuron interaction
  • pharmacological therapy
  • gene therapy
  • neuromodulation
  • regenerative medicine

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Published Papers (2 papers)

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25 pages, 7344 KiB  
Article
The Burning Pain Transcriptome in the Mouse Primary Somatosensory Cortex
by Virág Erdei, Zoltán Mészár and Angelika Varga
Int. J. Mol. Sci. 2025, 26(8), 3538; https://doi.org/10.3390/ijms26083538 - 9 Apr 2025
Viewed by 146
Abstract
Our previous research has demonstrated that the spinal cord undergoes epigenetic and molecular alterations following non-severe burn injury (BI). However, the primary somatosensory cortex (S1), crucial for pain perception, remains unexplored in this context. Here, we investigated transcriptomic alterations in the S1 cortex [...] Read more.
Our previous research has demonstrated that the spinal cord undergoes epigenetic and molecular alterations following non-severe burn injury (BI). However, the primary somatosensory cortex (S1), crucial for pain perception, remains unexplored in this context. Here, we investigated transcriptomic alterations in the S1 cortex of mice subjected to BI or formalin application (FA) to the hind paw, utilizing RNA sequencing (RNA-seq) one hour after injury. RNA-seq identified 1116 differentially expressed genes (DEGs) in BI and 136 DEGs in formalin-induced inflammatory pain. Notably, 82.4% of DEGs in BI and 32.4% in FA were downregulated. A total of 42 upregulated and 17 downregulated overlapping DEGs were identified, indicating significant differences in the cortical processing of pain based on its origins. Gene Ontology analysis reveals that BI upregulated mitochondrial functions and ribosome synthesis, whereas axon guidance, synaptic plasticity, and neurotransmission-related processes were downregulated. By contrast, formalin treatment mainly impacted metabolic processes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis highlights the significance of retrograde endocannabinoid signaling (REC) in the response to burn injury. These findings demonstrate that transcriptomic remodeling in the S1 cortex is dependent on the sensory modality and suggest that the REC network is activated during acute pain responses following BI. Full article
(This article belongs to the Special Issue Pain: From Molecular Basis to Therapy)
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Review

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14 pages, 716 KiB  
Review
Efficacy of Sodium Channel-Selective Analgesics in Postoperative, Neuralgia, and Neuropathy-Related Pain Management: A Systematic Review and Literature Review
by Athena Brooks, Anna Hornbach, Jade E. Smith, Noelle C. Garbaccio, Nathan Keller, Jessica Lemke, Jose A. Foppiani, Dominika Gavlasova, Theodore C. Lee, Marie-Claire Buckley, Umar Choudry and Samuel J. Lin
Int. J. Mol. Sci. 2025, 26(6), 2460; https://doi.org/10.3390/ijms26062460 - 10 Mar 2025
Viewed by 730
Abstract
Postoperative pain is a prevalent problem, often lasting from days to years. To minimize opioid use and associated risks of dependency, Enhanced Recovery After Surgery (ERAS) protocols increasingly incorporate multimodal analgesics. Sodium channel-selective blockers are a promising non-opioid alternative, yet their application in [...] Read more.
Postoperative pain is a prevalent problem, often lasting from days to years. To minimize opioid use and associated risks of dependency, Enhanced Recovery After Surgery (ERAS) protocols increasingly incorporate multimodal analgesics. Sodium channel-selective blockers are a promising non-opioid alternative, yet their application in postoperative pain remains underexplored. This systematic review evaluates their efficacy in managing postoperative, neuropathic, and neuralgia-related pain. A systematic review was conducted using controlled keywords across multiple databases to identify studies on sodium channel-selective blockers published up to 2024. Eligible studies included clinical trials, observational studies, case series, and reports involving patients aged 18 or older. Data were extracted on therapeutic outcomes, dosages, complications, and comparisons with other analgesics. Five studies met the inclusion criteria, involving 804 patients, 81.58% of whom were women. One study addressed postoperative pain, while the remaining five focused on neuropathy- and neuralgia-related pain. All studies reported significant pain reduction in at least one treatment group compared with placebo. In the study on postoperative pain, the sodium channel-selective blocker significantly reduced pain scores without requiring opioid analgesia. Across all studies, only two patients needed concomitant opioid therapy, and one discontinued treatment due to adverse effects. Dosages varied, with no reports of severe complications. Comparative analyses showed that sodium channel-selective blockers were as effective, if not superior, to traditional pain medications in reducing pain intensity. Sodium channel-selective blockers demonstrate significant potential in pain management with minimal opioid reliance. While effective for neuropathic pain, further studies are essential to validate their role in acute postoperative settings and refine their use in multimodal analgesia regimens. Full article
(This article belongs to the Special Issue Pain: From Molecular Basis to Therapy)
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