Spinal TRPA1 Contributes to the Mechanical Hypersensitivity Effect Induced by Netrin-1

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Wei , H , Ailanen , L , Morales , M , Koivisto , A & Pertovaara , A 2022 , ' Spinal TRPA1 Contributes to the Mechanical Hypersensitivity Effect Induced by Netrin-1 ' , International Journal of Molecular Sciences , vol. 23 , no. 12 , 6629 . https://doi.org/10.3390/ijms23126629

Title: Spinal TRPA1 Contributes to the Mechanical Hypersensitivity Effect Induced by Netrin-1
Author: Wei, Hong; Ailanen, Liisa; Morales, Miguel; Koivisto, Ari; Pertovaara, Antti
Contributor organization: Department of Physiology
University of Helsinki
Faculty of Medicine
Antti Pertovaara / Principal Investigator
Date: 2022-06
Language: eng
Number of pages: 16
Belongs to series: International Journal of Molecular Sciences
ISSN: 1422-0067
DOI: https://doi.org/10.3390/ijms23126629
URI: http://hdl.handle.net/10138/346388
Abstract: Netrin-1, a chemoattractant expressed by floor plate cells, and one of its receptors (deleted in colorectal cancer) has been associated with pronociceptive actions in a number of pain conditions. Here, we addressed the question of whether spinal TRPC4/C5 or TRPA1 are among the downstream receptors contributing to pronociceptive actions induced by netrin-1. The experiments were performed on rats using a chronic intrathecal catheter for administration of netrin-1 and antagonists of TRPC4/C5 or TRPA1. Pain sensitivity was assessed behaviorally by using mechanical and heat stimuli. Effect on the discharge rate of rostral ventromedial medullary (RVM) pain control neurons was studied in lightly anesthetized animals. Netrin-1, in a dose-related fashion, induced mechanical hypersensitivity that lasted up to three weeks. Netrin-1 had no effect on heat nociception. Mechanical hypersensitivity induced by netrin-1 was attenuated by TRPA1 antagonist Chembridge-5861528 and by the control analgesic compound pregabalin both during the early (first two days) and late (third week) phase of hypersensitivity. TRPC4/C5 antagonist ML-204 had a weak antihypersensitivity effect that was only in the early phase, whereas TRPC4/C5 antagonist HC-070 had no effect on hypersensitivity induced by netrin-1. The discharge rate in pronociceptive ON-like RVM neurons was increased by netrin-1 during the late but not acute phase, whereas netrin-1 had no effect on the discharge rate of antinociceptive RVM OFF-like neurons. The results suggest that spinal TRPA1 receptors and pronociceptive RVM ON-like neurons are involved in the maintenance of submodality-selective pronociceptive actions induced by netrin-1 in the spinal cord.
Subject: netrin-1
TRPA1 receptors
mechanical hypersensitivity
medullary pain control neuron
spinal cord
3111 Biomedicine
1182 Biochemistry, cell and molecular biology
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

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