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Homer1a inhibits caspase-6 signaling to attenuate inflammatory pain in the spinal dorsal horn.

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Title: Homer1a inhibits caspase-6 signaling to attenuate inflammatory pain in the spinal dorsal horn.
Authors: Zhao W; Department of Rheumatology, Children's Hospital of Soochow University, China., Song X; Department of Rheumatology, Children's Hospital of Soochow University, China., Yu M; Department of Rheumatology, Children's Hospital of Soochow University, China., Jiang K; Department of Anesthesiology, First Affiliated Hospital of Soochow University, China.
Source: The Journal of international medical research [J Int Med Res] 2025 Nov; Vol. 53 (11), pp. 3000605251395448. Date of Electronic Publication: 2025 Nov 18.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Sage Publications Country of Publication: England NLM ID: 0346411 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1473-2300 (Electronic) Linking ISSN: 03000605 NLM ISO Abbreviation: J Int Med Res Subsets: MEDLINE
Imprint Name(s): Publication: Nov. 2012- : London : Sage Publications
Original Publication: Northampton, Eng., Cambridge Medical Publications ltd.
MeSH Terms: Homer Scaffolding Proteins*/metabolism , Homer Scaffolding Proteins*/genetics , Signal Transduction* , Inflammation*/chemically induced , Inflammation*/pathology , Inflammation*/complications , Inflammation*/metabolism , Caspase 6*/metabolism , Spinal Cord Dorsal Horn*/metabolism , Spinal Cord Dorsal Horn*/pathology , Pain*/pathology , Pain*/metabolism , Pain*/chemically induced, Animals ; Male ; Rats ; Tumor Necrosis Factor-alpha/metabolism ; Rats, Sprague-Dawley ; Carrageenan/toxicity ; Disease Models, Animal
Abstract: ObjectiveThis study aimed to investigate the effect of Homer1a on caspase-6/tumor necrosis factor-alpha signaling pathway in an inflammatory pain model. We sought to determine whether Homer1a could alleviate nociceptive hypersensitivity by inhibiting the activation of the caspase-6/tumor necrosis factor-alpha signaling pathway.MethodsAn inflammatory pain model was established by unilateral plantar injection of carrageenan in rats. The hypothesis was tested using behavioral and immunological approaches.ResultsIn rats with carrageenan-induced hind paw inflammation, pain hypersensitivity was exacerbated, accompanied by an upregulation of Homer1a and activation of the caspase-6/tumor necrosis factor-alpha signaling pathway. Intrathecal administration of the caspase-6 inhibitor Z-valine-glutamic acid-isoleucine-aspartic acid-fluoromethyl ketone significantly attenuated microglial activation, tumor necrosis factor-alpha release, and thermal hypersensitivity but had no effect on Homer1a expression. Lentiviral overexpression of Homer1a reduced pain hypersensitivity and concurrently inhibited the caspase-6/tumor necrosis factor-alpha signaling pathway.ConclusionsThe present study demonstrates that Homer1a activation suppresses the caspase-6/tumor necrosis factor-alpha signaling pathway and alleviates thermal hypersensitivity in a rat model of inflammatory pain. These findings suggest that the Homer1a/caspase-6 signaling axis may represent a promising therapeutic target for inflammatory pain management.
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Contributed Indexing: Keywords: Homer1a; caspase-6; inflammatory pain; microglia; tumor necrosis factor-alpha
Substance Nomenclature: 0 (Homer Scaffolding Proteins)
0 (Tumor Necrosis Factor-alpha)
EC 3.4.22.- (Caspase 6)
9000-07-1 (Carrageenan)
Entry Date(s): Date Created: 20251119 Date Completed: 20251119 Latest Revision: 20251123
Update Code: 20251123
PubMed Central ID: PMC12627368
DOI: 10.1177/03000605251395448
PMID: 41254471
Database: MEDLINE
Description
Abstract:ObjectiveThis study aimed to investigate the effect of Homer1a on caspase-6/tumor necrosis factor-alpha signaling pathway in an inflammatory pain model. We sought to determine whether Homer1a could alleviate nociceptive hypersensitivity by inhibiting the activation of the caspase-6/tumor necrosis factor-alpha signaling pathway.MethodsAn inflammatory pain model was established by unilateral plantar injection of carrageenan in rats. The hypothesis was tested using behavioral and immunological approaches.ResultsIn rats with carrageenan-induced hind paw inflammation, pain hypersensitivity was exacerbated, accompanied by an upregulation of Homer1a and activation of the caspase-6/tumor necrosis factor-alpha signaling pathway. Intrathecal administration of the caspase-6 inhibitor Z-valine-glutamic acid-isoleucine-aspartic acid-fluoromethyl ketone significantly attenuated microglial activation, tumor necrosis factor-alpha release, and thermal hypersensitivity but had no effect on Homer1a expression. Lentiviral overexpression of Homer1a reduced pain hypersensitivity and concurrently inhibited the caspase-6/tumor necrosis factor-alpha signaling pathway.ConclusionsThe present study demonstrates that Homer1a activation suppresses the caspase-6/tumor necrosis factor-alpha signaling pathway and alleviates thermal hypersensitivity in a rat model of inflammatory pain. These findings suggest that the Homer1a/caspase-6 signaling axis may represent a promising therapeutic target for inflammatory pain management.
ISSN:1473-2300
DOI:10.1177/03000605251395448