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. 2007 Oct 29:3:31.
doi: 10.1186/1744-8069-3-31.

Marked attenuation of inflammatory mediator-induced C-fiber sensitization for mechanical and hypotonic stimuli in TRPV4-/- mice

Xiaojie Chen  1 , Nicole Alessandri-Haber, Jon D Levine
Affiliations

Marked attenuation of inflammatory mediator-induced C-fiber sensitization for mechanical and hypotonic stimuli in TRPV4-/- mice

Xiaojie Chen et al. Mol Pain. .

Abstract

Inflammatory mediators can directly sensitize primary afferent nociceptors to mechanical and osmotic stimuli. Sensitized nociceptors have a lowered threshold of activation and increased spontaneous activity, which result in symptoms of hyperalgesia and pain, respectively. The transient receptor potential vanilloid 4 (TRPV4) ligand-gated ion channel has been implicated in the hyperalgesia for mechanical and osmotic stimuli associated with inflammatory states. To investigate whether TRPV4 directly contributes to the mechanisms of inflammatory mediator sensitization of C-fiber nociceptors, we compared the effect of the injection of simplified inflammatory soup (prostaglandin E2 and serotonin) into the mechanical receptive fields of C-fibers in TRPV4+/+ and TRPV4-/- mice in vivo. Following the injection of the soup, the percentage of C-fibers responding to a hypotonic stimulus and the magnitude of the response was significantly greater in TRPV4+/+ mice compared to TRPV4-/- mice. Moreover, in response to simplified inflammatory soup only C-fibers from TRPV4+/+ mice exhibited increased spontaneous activity and decreased mechanical threshold. These marked impairments in the response of C-fibers in TRPV4-/- mice demonstrate the importance of TRPV4 in nociceptor sensitization; we suggest that TRPV4, as TRPV1, underlies the nociceptive effects of multiple inflammatory mediators on primary afferent.

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Figures

Figure 1
Figure 1
The average time course of the response of C-fibers during the 60 sec period after injection of simplified inflammatory soup was not significantly different in TRPV4+/+ and TRPV4-/- mice (unpaired t-test, p > 0.05). The bin width is 1 sec. A. The open bars represent activity evoked by simplified inflammatory soup in TRPV4+/+ C-fibers (n = 11), and B. The filled bars represent action potentials evoked in TRPV4-/- C-fibers (n = 13).
Figure 2
Figure 2
A. On-going activity in C-fibers before (open bar) and after (filled bar) injection of simplified inflammatory soup into each fiber's mechanical receptive field was significantly increased in TRPV4+/+ (n = 11, paired t-test, * p < 0.05) but not TRPV4-/- mice (n = 13, paired t-test, p > 0.05). B. The mechanical threshold of C-fibers in TRPV4+/+ (open bar, n = 11) produced by intradermal injection of simplified inflammatory soup was statistically significant (Wilcoxon matched test, * p < 0.05). However, simplified inflammatory soup did not significantly change mechanical threshold of C-fibers in TRPV4-/- mice (filled bars, n = 13, Wilcoxon matched test, p > 0.05). The change in mechanical threshold of C-fibers after simplified inflammatory soup was significantly greater in TRPV4+/+ than TRPV4-/- C-fibers (χ2 test, * p < 0.05).
Figure 3
Figure 3
Upper panel, response of a TRPV4+/+ C-fiber to hypotonic solution 15 min after injection of simplified inflammatory soup. Arrow indicates the time of injection of hypotonic solution. Lower panel, the average time course of the response of C-fibers during the first 60 sec after injection of hypotonic solution in TRPV4+/+ mice (open bar, n = 11). The bin width is 1 sec. B. Upper panel, response of a TRPV4-/- C-fiber to hypotonic solution after injection of simplified inflammatory soup. Lower panel, the average time course of the response of C-fibers during the first 60 sec after injection of hypotonic solution in TRPV4-/- mice (filled bars, n = 9).
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References

    1. Liedtke W, Choe Y, Marti-Renom MA, Bell AM, Denis CS, Sali A, Hudspeth AJ, Friedman JM, Heller S. Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor. Cell. 2000;103:525–535. doi: 10.1016/S0092-8674(00)00143-4. - DOI - PMC - PubMed
    1. Strotmann R, Harteneck C, Nunnenmacher K, Schultz G, Plant TD. OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity. Nat Cell Biol. 2000;2:695–702. doi: 10.1038/35036318. - DOI - PubMed
    1. Suzuki M, Watanabe Y, Oyama Y, Mizuno A, Kusano E, Hirao A, Ookawara S. Localization of mechanosensitive channel TRPV4 in mouse skin. Neurosci Lett. 2003;353:189–192. doi: 10.1016/j.neulet.2003.09.041. - DOI - PubMed
    1. Alessandri-Haber N, Dina OA, Yeh JJ, Parada CA, Reichling DB, Levine JD. Transient receptor potential vanilloid 4 is essential in chemotherapy-induced neuropathic pain in the rat. J Neurosci. 2004;24:4444–4452. doi: 10.1523/JNEUROSCI.0242-04.2004. - DOI - PMC - PubMed
    1. Liedtke W, Friedman JM. Abnormal osmotic regulation in trpv4-/- mice. Proc Natl Acad Sci U S A. 2003;100:13698–13703. doi: 10.1073/pnas.1735416100. - DOI - PMC - PubMed

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