1. ATF2, but not ATF3, participates in the maintenance of nerve injury-induced tactile allodynia and thermal hyperalgesia.
- Author
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Salinas-Abarca AB, Velazquez-Lagunas I, Franco-Enzástiga Ú, Torres-López JE, Rocha-González HI, and Granados-Soto V
- Subjects
- Activating Transcription Factor 2 genetics, Activating Transcription Factor 3 genetics, Animals, Calcitonin Gene-Related Peptide metabolism, Disease Models, Animal, Female, Ganglia, Spinal metabolism, Ganglia, Spinal pathology, Gene Expression Regulation, Lectins metabolism, Male, Microscopy, Confocal, Pain Measurement, Peripheral Nerve Injuries complications, Peripheral Nerve Injuries pathology, Phosphopyruvate Hydratase metabolism, RNA, Small Interfering administration & dosage, Rats, Rats, Wistar, Spinal Nerves metabolism, Spinal Nerves pathology, Touch physiology, Activating Transcription Factor 2 metabolism, Activating Transcription Factor 3 metabolism, Hyperalgesia etiology, Hyperalgesia metabolism
- Abstract
Transcription factors are proteins that modulate the transcriptional rate of target genes in the nucleus in response to extracellular or cytoplasmic signals. Activating transcription factors 2 (ATF2) and 3 (ATF3) respond to environmental signals and maintain cellular homeostasis. There is evidence that inflammation and nerve injury modulate ATF2 and ATF3 expression. However, the function of these transcription factors in pain is unknown. The purpose of this study was to investigate the contribution of ATF2 and ATF3 to nerve injury-induced neuropathic pain. L5/6 spinal nerve ligation induced tactile allodynia and thermal hyperalgesia. Moreover, nerve damage enhanced ATF2 and ATF3 protein expression in injured L5/6 dorsal root ganglia and spinal cord but not in uninjured L4 dorsal root ganglia. Nerve damage also enhanced ATF2 immunoreactivity in dorsal root ganglia and spinal cord 7 to 21 days post-injury. Repeated intrathecal post-treatment with a small-interfering RNA targeted against ATF2 (ATF2 siRNA) or anti-ATF2 antibody partially reversed tactile allodynia and thermal hyperalgesia. In contrast, ATF3 siRNA or anti-ATF3 antibody did not modify nociceptive behaviors. ATF2 immunoreactivity was found in dorsal root ganglia and spinal cord co-labeling with NeuN mainly in non-peptidergic (IB4
+ ) but also in peptidergic (CGRP+ ) neurons. ATF2 was found mainly in small- and medium-sized neurons. These results suggest that ATF2, but not ATF3, is found in strategic sites related to spinal nociceptive processing and participates in the maintenance of neuropathic pain in rats.- Published
- 2018
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