ArticleNeuroscience2016
Extracellular matrix hyaluronan signals via its CD44 receptor in the increased responsiveness to mechanical stimulation.
Article in Neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 37 citations in OpenAlex.
- Effects of Intra-Articular Administration of High-Molecular-Weight Linear Hyaluronic Acid on Synovial Fluid Characteristics and Joint Environment.Antioxidants (Basel, Switzerland) · 2026Article
- Human birth tissue products for pathological pain: mechanisms, evidence, and translational outlook.Journal of translational medicine · 2026Review
- Exploring promising biomarkers based on pathogenic mechanisms in interstitial cystitis/bladder pain syndrome.Nature reviews. Urology · 2026Review
- Bridging Temporomandibular Joint Structure, Function, and Pain: An Integrated Multiscale Perspective.Journal of dental research · 2026Review
- Eicosapentaenoic acid restores inflammation-induced changes in chondrocyte mechanics by suppressing the NF-κB p65/CD44 signaling pathway and attenuates osteoarthritis.Experimental & molecular medicine · 2025Article
- CD44 signaling in skin wound healing and regeneration.Journal of translational medicine · 2025Review
- Hyaluronan: An Architect and Integrator for Cancer and Neural Diseases.International journal of molecular sciences · 2025Review
- Article
- Tug of war: Understanding the dynamic interplay of tumor biomechanical environment on dendritic cell function.Mechanobiology in medicine · 2024Review
- Hyaluronidase-induced matrix remodeling contributes to long-term synaptic changes.Frontiers in neural circuits · 2024Article
- Allometrically scaling tissue forces drive pathological foreign-body responses to implants via Rac2-activated myeloid cells.Nature biomedical engineering · 2023Article
- Aggrecan and Hyaluronan: The Infamous Cartilage Polyelectrolytes - Then and Now.Advances in experimental medicine and biology · 2023Article
- Peripheralized sepiapterin reductase inhibition as a safe analgesic therapy.Frontiers in pharmacology · 2023Review
- Hyaluronan homeostasis and its role in pain and muscle stiffness.PM & R : the journal of injury, function, and rehabilitation · 2022Review
- Action of Hyaluronic Acid as a Damage-Associated Molecular Pattern Molecule and Its Function on the Treatment of Temporomandibular Disorders.Frontiers in pain research (Lausanne, Switzerland) · 2022Review
- PI3Kγ/AKT Signaling in High Molecular Weight Hyaluronan (HMWH)-Induced Anti-Hyperalgesia and Reversal of Nociceptor Sensitization.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Sexually Dimorphic Role of Toll-like Receptor 4 (TLR4) in High Molecular Weight Hyaluronan (HMWH)-induced Anti-hyperalgesia.The journal of pain · 2021Article
- Article
- Diverse Roles for Hyaluronan and Hyaluronan Receptors in the Developing and Adult Nervous System.International journal of molecular sciences · 2020Review
- Mechanisms Mediating High-Molecular-Weight Hyaluronan-Induced Antihyperalgesia.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
We propose that the extracellular matrix (ECM) signals CD44, a hyaluronan receptor, to increase the responsiveness to mechanical stimulation in the rat hind paw. We report that intradermal injection of hyaluronidase induces mechanical hyperalgesia, that is inhibited by co-administration of a CD44 receptor antagonist, A5G27. The intradermal injection of low (LMWH) but not high (HMWH) molecular weight hyaluronan also induces mechanical hyperalgesia, an effect that was attenuated by pretreatment with HMWH or A5G27. Pretreatment with HMWH also attenuated the hyperalgesia induced by hyaluronidase. Similarly, intradermal injection of A6, a CD44 receptor agonist, produced hyperalgesia that was inhibited by HMWH and A5G27. Inhibitors of protein kinase A (PKA) and Src, but not protein kinase C (PKC), significantly attenuated the hyperalgesia induced by both A6 and LMWH. Finally, to determine if CD44 receptor signaling is involved in a preclinical model of inflammatory pain, we evaluated the effect of A5G27 and HMWH on the mechanical hyperalgesia associated with the inflammation induced by carrageenan. Both A5G27 and HMWH attenuated carrageenan-induced mechanical hyperalgesia. Thus, while LMWH acts at its cognate receptor, CD44, to induce mechanical hyperalgesia, HMWH acts at the same receptor as an antagonist. That the local administration of HMWH or A5G27 inhibits carrageenan-induced hyperalgesia supports the suggestion that carrageenan produces changes in the ECM that contributes to inflammatory pain. These studies define a clinically relevant role for signaling by the hyaluronan receptor, CD44, in increased responsiveness to mechanical stimulation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.