Expression of TRPV1 channels after nerve injury provides an essential delivery tool for neuropathic pain attenuation.

Zakir, H.M. and Mostafeezur, R.M. and Suzuki, A. and Hitomi, S. and Suzuki, I. and Maeda, T. and Seo, K. and Yamada, Y. and Yamamura, K. and Lev, S. and Binshtok, A.M. and Iwata, K. and Kitagawa, J. (2012) Expression of TRPV1 channels after nerve injury provides an essential delivery tool for neuropathic pain attenuation. PLoS ONE. ISSN 1932-6203,

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Abstract

Increased expression of the transient receptor potential vanilloid 1 (TRPV1) channels, following nerve injury, may facilitate the entry of QX-314 into nociceptive neurons in order to achieve effective and selective pain relief. In this study we hypothesized that the level of QX-314/capsaicin (QX-CAP)--induced blockade of nocifensive behavior could be used as an indirect in-vivo measurement of functional expression of TRPV1 channels. We used the QX-CAP combination to monitor the functional expression of TRPV1 in regenerated neurons after inferior alveolar nerve (IAN) transection in rats. We evaluated the effect of this combination on pain threshold at different time points after IAN transection by analyzing the escape thresholds to mechanical stimulation of lateral mental skin. At 2 weeks after IAN transection, there was no QX-CAP mediated block of mechanical hyperalgesia, implying that there was no functional expression of TRPV1 channels. These results were confirmed immunohistochemically by staining of regenerated trigeminal ganglion (TG) neurons. This suggests that TRPV1 channel expression is an essential necessity for the QX-CAP mediated blockade. Furthermore, we show that 3 and 4 weeks after IAN transection, application of QX-CAP produced a gradual increase in escape threshold, which paralleled the increased levels of TRPV1 channels that were detected in regenerated TG neurons. Immunohistochemical analysis also revealed that non-myelinated neurons regenerated slowly compared to myelinated neurons following IAN transection. We also show that TRPV1 expression shifted towards myelinated neurons. Our findings suggest that nerve injury modulates the TRPV1 expression pattern in regenerated neurons and that the effectiveness of QX-CAP induced blockade depends on the availability of functional TRPV1 receptors in regenerated neurons. The results of this study also suggest that the QX-CAP based approach can be used as a new behavioral tool to detect dynamic changes in TRPV1 expression, in various pathological conditions.

Item Type: Article
Funders: UNSPECIFIED
Uncontrolled Keywords: TRPV1 channels
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
R Medicine > RK Dentistry
Divisions: Faculty of Dentistry > Dept of Oral Biology
Depositing User: Dr Mohammad Zakir Hossain
Date Deposited: 22 Oct 2013 03:54
Last Modified: 04 Jul 2017 07:40
URI: http://eprints.um.edu.my/id/eprint/8509

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