Nociception in a Progressive Multiple Sclerosis Model in Mice Is Dependent on Spinal TRPA1 Channel Activation

Autor: Gabriele Cheiran Pereira, Maria Fernanda Pessano Fialho, Camila Duarte Ritter, Débora Denardin Lückemeyer, Sabrina Qader Kudsi, Sara Marchesan Oliveira, Caren Tatiane de David Antoniazzi, Gabriela Trevisan, Amanda Spring de Almeida, Juliano Ferreira, Vitória Loreto Pereira, Diéssica Padilha Dalenogare
Rok vydání: 2020
Předmět:
Nociception
0301 basic medicine
Dipyrone
Pregabalin
Pharmacology
Mice
chemistry.chemical_compound
0302 clinical medicine
Oximes
TRPA1 Cation Channel
Analgesics
Thioctic Acid
biology
Experimental autoimmune encephalomyelitis
food and beverages
Up-Regulation
Allodynia
Spinal Cord
Neurology
Hyperalgesia
Neuropathic pain
Female
medicine.symptom
Agonist
Encephalomyelitis
Autoimmune
Experimental
medicine.drug_class
Neuroscience (miscellaneous)
Nerve Tissue Proteins
Myelin oligodendrocyte glycoprotein
03 medical and health sciences
Cellular and Molecular Neuroscience
medicine
Animals
Neuroinflammation
business.industry
Acetophenones
NADPH Oxidases
Oligonucleotides
Antisense
medicine.disease
Peptide Fragments
Mice
Inbred C57BL
Oxidative Stress
030104 developmental biology
chemistry
Purines
Apocynin
biology.protein
Neuralgia
Acetanilides
Myelin-Oligodendrocyte Glycoprotein
business
Antipyrine
030217 neurology & neurosurgery
Zdroj: Molecular Neurobiology. 57:2420-2435
ISSN: 1559-1182
0893-7648
Popis: Central neuropathic pain is a common untreated symptom in progressive multiple sclerosis (PMS) and is associated with poor quality of life and interference with patients’ daily activities. The neuroinflammation process and mitochondrial dysfunction in the PMS lesions generate reactive species. The transient potential receptor ankyrin 1 (TRPA1) has been identified as one of the major mechanisms that contribute to neuropathic pain signaling and can be activated by reactive compounds. Thus, the goal of our study was to evaluate the role of spinal TRPA1 in the central neuropathic pain observed in a PMS model in mice. We used C57BL/6 female mice (20–30 g), and the PMS model was induced by the experimental autoimmune encephalomyelitis (EAE) using mouse myelin oligodendrocyte glycoprotein (MOG35–55) antigen and CFA (complete Freund’s adjuvant). Mice developed progressive clinical score, with motor impairment observed after 15 days of induction. This model induced mechanical and cold allodynia and heat hyperalgesia which were measured up to 14 days after induction. The hypersensitivity observed was reduced by the administration of selective TRPA1 antagonists (HC-030031 and A-967079, via intrathecal and intragastric), antioxidants (α-lipoic acid and apocynin, via intrathecal and intragastric), and TRPA1 antisense oligonucleotide (via intrathecal). We also observed an increase in TRPA1 mRNA levels, NADPH oxidase activity, and 4-hydroxinonenal (a TRPA1 agonist) levels in spinal cord samples of PMS-EAE induced animals. In conclusion, these results support the hypothesis of the TRPA1 receptor involvement in nociception observed in a PMS-EAE model in mice.
Databáze: OpenAIRE
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