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Transient receptor potential vanilloid 4 is essential in chemotherapy-induced neuropathic pain in the rat.
J Neurosci. 2004 May 05; 24(18):4444-52.JN

Abstract

The development of treatments for neuropathic pain has been hindered by our limited understanding of the basic mechanisms underlying abnormalities in nociceptor hyperexcitability. We recently showed that the polymodal receptor transient receptor potential vanilloid 4 (TRPV4), a member of the transient receptor potential (TRP) family of ion channels, may play a role in inflammatory pain (Alessandri-Haber et al., 2003). The present study tested whether TRVP4 also contributes to neuropathic pain, using a rat model of Taxol-induced painful peripheral neuropathy. Taxol is the most widely used drug for the treatment of a variety of tumor types, but the dose of Taxol that can be tolerated is limited by the development of a small-fiber painful peripheral neuropathy. We found that Taxol treatment enhanced the nociceptive behavioral responses to both mechanical and hypotonic stimulation of the hind paw. Spinal administration of antisense oligodeoxynucleotides to TRPV4, which reduced the expression of TRPV4 in sensory nerve, abolished Taxol-induced mechanical hyperalgesia and attenuated hypotonic hyperalgesia by 42%. The enhancement of osmotic nociception involves sensitization of osmotransduction in primary afferents because osmotransduction was enhanced in cultured sensory neurons isolated from Taxol-treated rats. Taxol-induced TRPV4-mediated hyperalgesia and the enhanced osmotransduction in cultured nociceptors were dependent on integrin/Src tyrosine kinase signaling. These results suggest that TRPV4 plays a crucial role in a painful peripheral neuropathy, making it a very promising target for the development of a novel class of analgesics.

Authors+Show Affiliations

Division of Neurosciences, University of California San Francisco, San Francisco, California 94143-0440, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15128858

Citation

Alessandri-Haber, Nicole, et al. "Transient Receptor Potential Vanilloid 4 Is Essential in Chemotherapy-induced Neuropathic Pain in the Rat." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 24, no. 18, 2004, pp. 4444-52.
Alessandri-Haber N, Dina OA, Yeh JJ, et al. Transient receptor potential vanilloid 4 is essential in chemotherapy-induced neuropathic pain in the rat. J Neurosci. 2004;24(18):4444-52.
Alessandri-Haber, N., Dina, O. A., Yeh, J. J., Parada, C. A., Reichling, D. B., & Levine, J. D. (2004). Transient receptor potential vanilloid 4 is essential in chemotherapy-induced neuropathic pain in the rat. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 24(18), 4444-52.
Alessandri-Haber N, et al. Transient Receptor Potential Vanilloid 4 Is Essential in Chemotherapy-induced Neuropathic Pain in the Rat. J Neurosci. 2004 May 5;24(18):4444-52. PubMed PMID: 15128858.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transient receptor potential vanilloid 4 is essential in chemotherapy-induced neuropathic pain in the rat. AU - Alessandri-Haber,Nicole, AU - Dina,Olayinka A, AU - Yeh,Jenny J, AU - Parada,Carlos A, AU - Reichling,David B, AU - Levine,Jon D, PY - 2004/5/7/pubmed PY - 2004/9/4/medline PY - 2004/5/7/entrez SP - 4444 EP - 52 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J Neurosci VL - 24 IS - 18 N2 - The development of treatments for neuropathic pain has been hindered by our limited understanding of the basic mechanisms underlying abnormalities in nociceptor hyperexcitability. We recently showed that the polymodal receptor transient receptor potential vanilloid 4 (TRPV4), a member of the transient receptor potential (TRP) family of ion channels, may play a role in inflammatory pain (Alessandri-Haber et al., 2003). The present study tested whether TRVP4 also contributes to neuropathic pain, using a rat model of Taxol-induced painful peripheral neuropathy. Taxol is the most widely used drug for the treatment of a variety of tumor types, but the dose of Taxol that can be tolerated is limited by the development of a small-fiber painful peripheral neuropathy. We found that Taxol treatment enhanced the nociceptive behavioral responses to both mechanical and hypotonic stimulation of the hind paw. Spinal administration of antisense oligodeoxynucleotides to TRPV4, which reduced the expression of TRPV4 in sensory nerve, abolished Taxol-induced mechanical hyperalgesia and attenuated hypotonic hyperalgesia by 42%. The enhancement of osmotic nociception involves sensitization of osmotransduction in primary afferents because osmotransduction was enhanced in cultured sensory neurons isolated from Taxol-treated rats. Taxol-induced TRPV4-mediated hyperalgesia and the enhanced osmotransduction in cultured nociceptors were dependent on integrin/Src tyrosine kinase signaling. These results suggest that TRPV4 plays a crucial role in a painful peripheral neuropathy, making it a very promising target for the development of a novel class of analgesics. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/15128858/Transient_receptor_potential_vanilloid_4_is_essential_in_chemotherapy_induced_neuropathic_pain_in_the_rat_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=15128858 DB - PRIME DP - Unbound Medicine ER -