当前位置： SCI文献检索 > PAIN期刊下所有文献 > Psychophysical and vasomotor evidence for interdependency of TRPA1 and TRPV1-evoked nociceptive responses in human skin: an experimental study.

Psychophysical and vasomotor evidence for interdependency of TRPA1 and TRPV1-evoked nociceptive responses in human skin: an experimental study.

Abstract：

:The TRPA1 and TRPV1 receptors are important pharmaceutical targets for antipruritic and analgesic therapy. Obtaining further knowledge on their roles and interrelationship in humans is therefore crucial. Preclinical results are contradictory concerning coexpression and functional interdependency of TRPV1 and TRPA1, but no human evidence exists. This human experimental study investigated whether functional responses from the subpopulation of TRPA1 nociceptors could be evoked after defunctionalization of TRPV1 nociceptors by cutaneous application of high-concentration capsaicin. Two quadratic areas on each forearm were randomized to pretreatment with an 8% topical capsaicin patch or vehicle for 24 hours. Subsequently, areas were provoked by transdermal 1% topical capsaicin (TRPV1 agonist) or 10% topical allyl isothiocyanate ("AITC," a TRPA1 agonist), delivered by 12 mm Finn chambers. Evoked pain intensities were recorded during pretreatments and chemical provocations. Quantitative sensory tests were performed before and after provocations to assess changes of heat pain sensitivity. Imaging of vasomotor responses was used to assess neurogenic inflammation after the chemical provocations. In the capsaicin-pretreated areas, both the subsequent 1% capsaicin- and 10% AITC-provoked pain was inhibited by 92.9 ± 2.5% and 86.9 ± 5.0% (both: P < 0.001), respectively. The capsaicin-ablated skin areas showed significant heat hypoalgesia at baseline (P < 0.001) as well as heat antihyperalgesia, and inhibition of neurogenic inflammation evoked by both 1% capsaicin and 10% AITC provocations (both: P < 0.001). Ablation of cutaneous capsaicin-sensitive afferents caused consistent and equal inhibition of both TRPV1- and TRPA1-provoked responses assessed psychophysically and by imaging of vasomotor responses. This study suggests that TRPA1 nociceptive responses in human skin strongly depend on intact capsaicin-sensitive, TRPV1 fibers.

journal_name

Pain

journal_title

Pain

authors

Nielsen TA,Eriksen MA,Gazerani P,Andersen HH

doi

10.1097/j.pain.0000000000001298

subject

Has Abstract

pub_date

2018-10-01 00:00:00

pages

1989-2001

issue

eissn

0304-3959

issn

1872-6623

journal_volume

159

pub_type

杂志文章

在线工具

Psychophysical and vasomotor evidence for interdependency of TRPA1 and TRPV1-evoked nociceptive responses in human skin: an experimental study.