Novel Insights into Molecular and Cellular Mechanisms Underlying Chronic Pain

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: 30 March 2026 | Viewed by 638

Special Issue Editor


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Guest Editor
Department of Pharmacology and Neuroscience, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
Interests: pain; pharmacology; brain

Special Issue Information

Dear Colleagues,

Chronic pain represents a major health issue and an unmet medical challenge. Despite increasing research efforts in this field, the mechanisms underlying pain and the chronification of pain remain poorly understood. Peripheral, spinal and supraspinal processes contribute to the development and maintenance of pain. Neuronal and non-neuronal factors play a pivotal role in pain signaling and its amplification, resulting in pain persistence. New insights into the mechanisms involved in pain are desperately needed in order to identify new therapeutic targets for pain management.

This Special Issue will address current knowledge gaps in relation to the cellular factors and molecular pathways involved in the pathophysiology of pain at the peripheral, spinal, and supraspinal levels and the associated sexual dimorphisms. We welcome articles exploring pain-related mechanisms and their therapeutic implications, with the goal of inspiring the development of efficient new clinical treatments.

Dr. Mariacristina Mazzitelli
Guest Editor

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Keywords

  • pain
  • pain management
  • sexual dimorphism
  • neurons
  • non-neuronal factors

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Published Papers (1 paper)

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Research

20 pages, 6612 KB  
Article
Spinal Dorsal Horn Neurons Receiving Descending Input from the Primary Somatosensory Cortex Contribute to Aβ Fiber-Induced Neuropathic Allodynia in Male Rats
by Sho Shinotsuka, Eriko I, Daichi Sueto, Kazuki Fujimori, Ken Yamaura and Makoto Tsuda
Cells 2025, 14(23), 1870; https://doi.org/10.3390/cells14231870 - 26 Nov 2025
Viewed by 460
Abstract
Mechanical allodynia is the predominant symptom of neuropathic pain following peripheral nerve injury (PNI) and is characterized by pain evoked by innocuous sensory signals transmitted through low-threshold mechanoreceptive primary afferents, including Aβ fibers. However, the underlying neural mechanisms remain insufficiently understood. Previous studies [...] Read more.
Mechanical allodynia is the predominant symptom of neuropathic pain following peripheral nerve injury (PNI) and is characterized by pain evoked by innocuous sensory signals transmitted through low-threshold mechanoreceptive primary afferents, including Aβ fibers. However, the underlying neural mechanisms remain insufficiently understood. Previous studies have suggested that the pathological conversion of tactile input into nociceptive signals involves maladaptive alterations in neural circuits and function within the spinal dorsal horn (SDH). Somatosensory processing and transmission in the SDH are regulated not only by local neuronal circuits but also by descending inputs from the brainstem and higher cortical regions. In this study, we show that chemogenetic silencing of descending neurons projecting directly from the primary somatosensory (S1) cortex to the SDH (S1→SDH neurons) suppresses both PNI-induced allodynia-like behavior and c-FOS expression in the superficial SDH observed in male rats where touch-sensing Aβ fibers were optogenetically activated. S1→SDH neurons were excitatory and preferentially targeted excitatory SDH neurons (S1→SDH neurons) broadly distributed across laminae I–V. S1→SDH neurons in the superficial laminae also received excitatory inputs from both Aβ fibers and inhibitory inputs from neuropeptide Y promoter active SDH neurons (NpyP+ neurons). Furthermore, loss of inhibition from NpyP+ neurons induced Aβ fiber-derived allodynia, which was attenuated by suppressing descending signaling from S1→SDH neurons to the SDH. Moreover, silencing S1→SDH neurons alleviated neuropathic allodynia. These findings identify a new corticospinal mechanism that contributes to Aβ fiber-mediated neuropathic allodynia and highlight the S1→SDH pathway as a potential therapeutic target. Full article
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