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Cited by 7Pain Mechanisms and TreatmentsOsteoarthritis Treatment and MechanismsNeuropeptides and Animal Physiology

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Substance P-neurokinin 1 receptor signal involves the development of osteoarthritis-induced chronic pain in rats

Kwon, Minji, Kim, Taemin, Park, Eui Ho, Song, Sunmi, Ok, Hogwang, Yoo, Heayeon, Nam, Dongyeon, Kim, Junesun·2025·Journal of Neuropathology & Experimental Neurology
DOI 10.1093/jnen/nlaf063
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Abstract

Chronic pain is a major symptom of osteoarthritis (OA). Substance P (SP) plays a role in inflammation and nociception, but its role in OA pain chronicity remains unclear. This study investigates whether SP-neurokinin 1 (NK1R) signal mediates the development of chronic pain in monosodium iodoacetate (MIA)-induced OA model rats. GR 82334 (GR), an NK1R antagonist, was injected intra-articularly 30 minutes before (pre-GR) or 1 day after (post-GR) MIA injection to examine the effects of NK1R blocking of early inflammation on chronic pain and neuroimmune interactions in the knee joint, dorsal root ganglion (DRG), and spinal dorsal horn (SDH). GR reduced edema and knee bending scores; post-GR treatment more effectively prevented paw withdrawal threshold reduction than pre-GR treatment. Early NK1R blocking suppressed the expression of CGRP, SP, and pro-inflammatory factors (CCL2, TNFα, IL-1β, and IL-6), and M1 macrophage activation in the knee joints at 14 days post-MIA. GR also reduced the expression of pro-inflammatory factors and M1 macrophage activation in the L3-5 DRGs and decreased the expression of CGRP, SP, and pro-inflammatory factors, and microglial activation in the L3-5 SDHs. These findings suggest that early SP-NK1R signal-mediated inflammation contributes to OA chronic pain progression via neuroimmune interactions.

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Metadata

Authors
Kwon, M., Kim, T., Park, E. H., Song, S., Ok, H., Yoo, H., Nam, D., & Kim, J.
Affiliations
Korea University (KR)
Corresponding author
Kim, Junesun
ORCID
Venue
Journal of Neuropathology & Experimental Neurology
Publisher
Oxford University Press (OUP)
Published
2025-07-04
Volume
84
Issue
10
Pages
879-891
ISSN
  • 0022-3069 (ISSN-L)
  • 1554-6578
DOI
10.1093/jnen/nlaf063
OpenAlex
W4412034164
Cited by
7
References
1
Citations by year
2026: 6 · 2025: 1
FWCI
4.53
Type
journal article
Language
en
Open access
closed
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • Journal of Neuropathology & Experimental Neurology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Basic Science Research Program
  • National Research Foundation of Korea (RS-2022-NR067566)
  • Ministry of Science
  • ICT & Future Planning (2019R1I1A2A01060115)
  • Pioneer Research Center Program
  • Ministry of Education (RS-2024-00412358)
Topics
  • Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
  • Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords
substance P, neurokinin-1 receptor, osteoarthritis, chronic pain, monosodium iodoacetate, NK1 receptor antagonists, neuroimmune interactions, dorsal root ganglia, dorsal horn, microglial activation, M1 macrophage activation, calcitonin gene-related peptide, inflammatory cytokines, knee joint inflammation, nociception
MeSH terms
Animals, Ganglia, Spinal, Male, Osteoarthritis, Substance P, Signal Transduction, Rats, Sprague-Dawley, Receptors, Neurokinin-1, Rats, Chronic Pain, Neurokinin-1 Receptor Antagonists

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CoChat. (2026). Citation check: Substance P-neurokinin 1 receptor signal involves the development of osteoarthritis-induced chronic pain in rats. https://app.cochat.ai/papers/10.1093/jnen/nlaf063
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Kwon, M., Kim, T., Park, E. H., Song, S., Ok, H., Yoo, H., Nam, D., & Kim, J. (2025). Substance P-neurokinin 1 receptor signal involves the development of osteoarthritis-induced chronic pain in rats. Journal of Neuropathology & Experimental Neurology. https://doi.org/10.1093/jnen/nlaf063