Tags

Type your tag names separated by a space and hit enter

A transient receptor potential vanilloid 4-dependent mechanism of hyperalgesia is engaged by concerted action of inflammatory mediators.
J Neurosci. 2006 Apr 05; 26(14):3864-74.JN

Abstract

The transient receptor potential vanilloid 4 (TRPV4) is a primary afferent transducer that plays a crucial role in neuropathic hyperalgesia for osmotic and mechanical stimuli, as well as in inflammatory mediator-induced hyperalgesia for osmotic stimuli. In view of the clinical importance of mechanical hyperalgesia in inflammatory states, the present study investigated the role of TRPV4 in mechanical hyperalgesia induced by inflammatory mediators and the second-messenger pathways involved. Intradermal injection of either the inflammogen carrageenan or a soup of inflammatory mediators enhanced the nocifensive paw-withdrawal reflex elicited by hypotonic or mechanical stimuli in rat. Spinal administration of TRPV4 antisense oligodeoxynucleotide blocked the enhancement without altering baseline nociceptive threshold. Similarly, in TRPV4(-/-) knock-out mice, inflammatory soup failed to induce any significant mechanical or osmotic hyperalgesia. In vitro investigation showed that inflammatory mediators engage the TRPV4-mediated mechanism of sensitization by direct action on dissociated primary afferent neurons. Additional behavioral observations suggested that multiple mediators are necessary to achieve sufficient activation of the cAMP pathway to engage the TRPV4-dependent mechanism of hyperalgesia. In addition, direct activation of protein kinase A or protein kinase C epsilon, two pathways that mediate inflammation-induced mechanical hyperalgesia, also induced hyperalgesia for both hypotonic and mechanical stimuli that was decreased by TRPV4 antisense and absent in TRPV4(-/-) mice. We conclude that TRPV4 plays a crucial role in the mechanical hyperalgesia that is generated by the concerted action of inflammatory mediators present in inflamed tissues.

Authors+Show Affiliations

Division of Neurosciences, Department of Oral and Maxillofacial Surgery, University of California, San Francisco, California 94143-0440, USA. haber@itsa.ucsf.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

16597741

Citation

Alessandri-Haber, Nicole, et al. "A Transient Receptor Potential Vanilloid 4-dependent Mechanism of Hyperalgesia Is Engaged By Concerted Action of Inflammatory Mediators." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 26, no. 14, 2006, pp. 3864-74.
Alessandri-Haber N, Dina OA, Joseph EK, et al. A transient receptor potential vanilloid 4-dependent mechanism of hyperalgesia is engaged by concerted action of inflammatory mediators. J Neurosci. 2006;26(14):3864-74.
Alessandri-Haber, N., Dina, O. A., Joseph, E. K., Reichling, D., & Levine, J. D. (2006). A transient receptor potential vanilloid 4-dependent mechanism of hyperalgesia is engaged by concerted action of inflammatory mediators. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 26(14), 3864-74.
Alessandri-Haber N, et al. A Transient Receptor Potential Vanilloid 4-dependent Mechanism of Hyperalgesia Is Engaged By Concerted Action of Inflammatory Mediators. J Neurosci. 2006 Apr 5;26(14):3864-74. PubMed PMID: 16597741.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A transient receptor potential vanilloid 4-dependent mechanism of hyperalgesia is engaged by concerted action of inflammatory mediators. AU - Alessandri-Haber,Nicole, AU - Dina,Olayinka A, AU - Joseph,Elizabeth K, AU - Reichling,David, AU - Levine,Jon D, PY - 2006/4/7/pubmed PY - 2006/4/28/medline PY - 2006/4/7/entrez SP - 3864 EP - 74 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J Neurosci VL - 26 IS - 14 N2 - The transient receptor potential vanilloid 4 (TRPV4) is a primary afferent transducer that plays a crucial role in neuropathic hyperalgesia for osmotic and mechanical stimuli, as well as in inflammatory mediator-induced hyperalgesia for osmotic stimuli. In view of the clinical importance of mechanical hyperalgesia in inflammatory states, the present study investigated the role of TRPV4 in mechanical hyperalgesia induced by inflammatory mediators and the second-messenger pathways involved. Intradermal injection of either the inflammogen carrageenan or a soup of inflammatory mediators enhanced the nocifensive paw-withdrawal reflex elicited by hypotonic or mechanical stimuli in rat. Spinal administration of TRPV4 antisense oligodeoxynucleotide blocked the enhancement without altering baseline nociceptive threshold. Similarly, in TRPV4(-/-) knock-out mice, inflammatory soup failed to induce any significant mechanical or osmotic hyperalgesia. In vitro investigation showed that inflammatory mediators engage the TRPV4-mediated mechanism of sensitization by direct action on dissociated primary afferent neurons. Additional behavioral observations suggested that multiple mediators are necessary to achieve sufficient activation of the cAMP pathway to engage the TRPV4-dependent mechanism of hyperalgesia. In addition, direct activation of protein kinase A or protein kinase C epsilon, two pathways that mediate inflammation-induced mechanical hyperalgesia, also induced hyperalgesia for both hypotonic and mechanical stimuli that was decreased by TRPV4 antisense and absent in TRPV4(-/-) mice. We conclude that TRPV4 plays a crucial role in the mechanical hyperalgesia that is generated by the concerted action of inflammatory mediators present in inflamed tissues. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/16597741/A_transient_receptor_potential_vanilloid_4_dependent_mechanism_of_hyperalgesia_is_engaged_by_concerted_action_of_inflammatory_mediators_ DB - PRIME DP - Unbound Medicine ER -