Increased susceptibility of annexin‐A1 null mice to nociceptive pain is indicative of a spinal antinociceptive action of annexin‐A1
Open accessAbstract
Background and purpose: Annexin‐A1 (ANXA1), a glucocorticoid‐regulated protein, mediates several of the anti‐inflammatory actions of the glucocorticoids. Previous studies demonstrated that ANXA1 is involved in pain modulation. The current study, using ANXA1 knockout mice (ANXA1−/−), is aimed at addressing the site and mechanism of the modulatory action of ANXA1 as well as possible involvement of ANXA1 in mediating the analgesic action of glucocorticoids. Experimental approach: The acetic acid‐induced writhing response was performed in ANXA1−/−and wild‐type (ANXA1+/+) mice with spinal and brain levels of prostaglandin E 2(PGE 2) examined in both genotypes. The effect of the ANXA1 peptomimetic Ac2‐26 as well as methylprednisolone on the writhing response and on spinal cord PGE 2 of ANXA1+/+and ANXA1−/−was compared. The expression of proteins involved in PGE 2 synthesis, cytosolic phospholipase A 2(cPLA 2) and cyclooxygenases (COXs), in the spinal cord of ANXA1+/+and ANXA1−/−was also compared. Key results: ANXA1−/−mice exhibited a significantly greater writhing response and increased spinal cord levels of PGE 2 compared with ANXA1+/+mice. Ac2‐26 produced analgesia and reduced spinal PGE 2 levels in ANXA1+/+and ANXA1−/−mice, whereas methylprednisolone reduced the writhing response and spinal PGE 2 levels in ANXA1+/+, but not in ANXA1−/−mice. The expression of cPLA 2, COX‐1, COX‐2 and COX‐3 in spinal cord tissues was upregulated in ANXA1−/−compared with ANXA1+/+. Conclusions and implications: We conclude that ANXA1 protein modulates nociceptive processing at the spinal level, by reducing synthesis of PGE 2 by modulating cPLA 2 and/or COX activity. The analgesic activity of methylprednisolone is mediated by spinal ANXA1. British Journal of Pharmacology(2008)154, 1135–1142; doi:10.1038/bjp.2008.166; published online 12 May 2008
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Using an antibody that recognizes the intron-1 sequence, the authors detected an intron-1 retaining protein in rodent CNS tissues.
“Using an antibody that recognizes the intron-1 sequence, we have also been able to detect an intron-1 retaining protein in rodent CNS tissues [23,43,44] (Figure 3).”
From Paracetamol (acetaminophen): A familiar drug with an unexplained mechanism of action (2021) · cites this paper as [43]
The Western blotting section says the authors used an anti-COX-3 antibody, and the Discussion reports detecting COX-3 protein in mouse spinal cord tissue. Our copy does not say that the antibody recognizes an intron-1 sequence or establish that the detected protein retains intron 1. No page number is available for these passages. (LLM, conf=0.84)
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- Authors
- Ayoub, S. S., Yazid, S., & Flower, R. J.
- Affiliations
- University of London (GB)
- Corresponding author
- Ayoub, S S
- ORCID
- Ayoub, S S
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2008-07
- Volume
- 154
- Issue
- 5
- Pages
- 1135-1142
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC2451045
- OpenAlex
- W2046146220
- Cited by
- 48
- References
- 45
- Citations by year
- 2026: 2 · 2025: 1 · 2023: 3 · 2022: 3 · 2021: 10 · 2020: 3 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 4 · 2014: 3 · 2013: 5 · 2012: 3
- FWCI
- 1.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust
- William Harvey Research Foundation
- Leverhulme Trust
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › S100 Proteins and Annexins
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Keywords
- annexin A1, nociceptive pain, spinal antinociception, prostaglandin E2, acetic acid-induced writhing, methylprednisolone, Ac2-26, cytosolic phospholipase A2, cyclooxygenase, cyclooxygenase-2, cyclooxygenase-1, COX-3, pain modulation
- MeSH terms
- Analgesics, Animals, Behavior, Animal, Disease Models, Animal, Female, Glucocorticoids, Male, Methylprednisolone, Mice, Inbred C57BL, Pain, Pain Measurement, Peptides, Prostaglandin-Endoperoxide Synthases, Spinal Cord, Dinoprostone, Signal Transduction, Annexin A1, Mice, Knockout, Acetic Acid, Mice, Phospholipases A2, Cytosolic
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