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Interaction of transient receptor potential vanilloid 4, integrin, and SRC tyrosine kinase in mechanical hyperalgesia.
J Neurosci. 2008 Jan 30; 28(5):1046-57.JN

Abstract

Although the transient receptor potential vanilloid 4 (TRPV4) has been implicated in the process of osmomechanical transduction, it appears to make little contribution to the normal somatosensory detection of mechanical stimuli. However, evidence suggests that it may play an important role in mechanical hyperalgesia. In the present study, we examined the common requirement for TRPV4 in mechanical hyperalgesia associated with diverse pain models and investigated whether the very close association observed between TRPV4 and mechanical hyperalgesia, regardless of etiology, reflects a close functional connection of TRPV4 with other molecules implicated in mechanical transduction. In models of painful peripheral neuropathy associated with vincristine chemotherapy, alcoholism, diabetes, and human immunodeficiency virus/acquired immune deficiency syndrome therapy, mechanical hyperalgesia was markedly reduced by spinal intrathecal administration of oligodeoxynucleotides antisense to TRPV4. Similarly, mechanical hyperalgesia induced by paclitaxel, vincristine, or diabetes was strongly reduced in TRPV4 knock-out mice. We also show that alpha2beta1 integrin and Src tyrosine kinase, which have been implicated in mechanical transduction, are important for the development of mechanical hyperalgesia, and that their contribution requires TRPV4. Furthermore, we establish a direct interaction between TRPV4, alpha2 integrin, and the Src tyrosine kinase Lyn in sensory neurons. We suggest that TRPV4 plays a role in mechanotransduction, as a component of a molecular complex that functions only in the setting of inflammation or nerve injury.

Authors+Show Affiliations

Department of Oral and Maxillofacial Surgery, University of California, San Francisco, San Francisco, California 94143-0440, USA. Nicole.Haber@ucsf.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

18234883

Citation

Alessandri-Haber, Nicole, et al. "Interaction of Transient Receptor Potential Vanilloid 4, Integrin, and SRC Tyrosine Kinase in Mechanical Hyperalgesia." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 28, no. 5, 2008, pp. 1046-57.
Alessandri-Haber N, Dina OA, Joseph EK, et al. Interaction of transient receptor potential vanilloid 4, integrin, and SRC tyrosine kinase in mechanical hyperalgesia. J Neurosci. 2008;28(5):1046-57.
Alessandri-Haber, N., Dina, O. A., Joseph, E. K., Reichling, D. B., & Levine, J. D. (2008). Interaction of transient receptor potential vanilloid 4, integrin, and SRC tyrosine kinase in mechanical hyperalgesia. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 28(5), 1046-57. https://doi.org/10.1523/JNEUROSCI.4497-07.2008
Alessandri-Haber N, et al. Interaction of Transient Receptor Potential Vanilloid 4, Integrin, and SRC Tyrosine Kinase in Mechanical Hyperalgesia. J Neurosci. 2008 Jan 30;28(5):1046-57. PubMed PMID: 18234883.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interaction of transient receptor potential vanilloid 4, integrin, and SRC tyrosine kinase in mechanical hyperalgesia. AU - Alessandri-Haber,Nicole, AU - Dina,Olayinka A, AU - Joseph,Elizabeth K, AU - Reichling,David B, AU - Levine,Jon D, PY - 2008/2/1/pubmed PY - 2008/2/20/medline PY - 2008/2/1/entrez SP - 1046 EP - 57 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J Neurosci VL - 28 IS - 5 N2 - Although the transient receptor potential vanilloid 4 (TRPV4) has been implicated in the process of osmomechanical transduction, it appears to make little contribution to the normal somatosensory detection of mechanical stimuli. However, evidence suggests that it may play an important role in mechanical hyperalgesia. In the present study, we examined the common requirement for TRPV4 in mechanical hyperalgesia associated with diverse pain models and investigated whether the very close association observed between TRPV4 and mechanical hyperalgesia, regardless of etiology, reflects a close functional connection of TRPV4 with other molecules implicated in mechanical transduction. In models of painful peripheral neuropathy associated with vincristine chemotherapy, alcoholism, diabetes, and human immunodeficiency virus/acquired immune deficiency syndrome therapy, mechanical hyperalgesia was markedly reduced by spinal intrathecal administration of oligodeoxynucleotides antisense to TRPV4. Similarly, mechanical hyperalgesia induced by paclitaxel, vincristine, or diabetes was strongly reduced in TRPV4 knock-out mice. We also show that alpha2beta1 integrin and Src tyrosine kinase, which have been implicated in mechanical transduction, are important for the development of mechanical hyperalgesia, and that their contribution requires TRPV4. Furthermore, we establish a direct interaction between TRPV4, alpha2 integrin, and the Src tyrosine kinase Lyn in sensory neurons. We suggest that TRPV4 plays a role in mechanotransduction, as a component of a molecular complex that functions only in the setting of inflammation or nerve injury. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/18234883/Interaction_of_transient_receptor_potential_vanilloid_4_integrin_and_SRC_tyrosine_kinase_in_mechanical_hyperalgesia_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=18234883 DB - PRIME DP - Unbound Medicine ER -