Social defeat stress-induced hyperalgesia is mediated by nav 1.8(+) nociceptive fibers

Author(s)

Pagliusi Jr, Marco ; Magayewski Bonet, Ivan Jose ^[1] ; Paes Lemes, Julia Borges ^[2] ; Lima Oliveira, Anna Lethicia ^[2] ; Carvalho, Nathalia Santos ^[2] ; Tambeli, Claudia Herrera ^[2] ; Parada, Carlos Amilcar ^[2] ; Sartori, Cesar Renato ^[2]

Affiliation

^[1] Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, 513 Parnassus Ave, Box 0440 S709, San Francisco, CA 94143 - USA

^[2] Pagliusi Jr, Jr., Marco, Univ Estadual Campinas, Dept Struct & Funct Biol, Rua Monteiro Lobato 255, Cidade Univ Zeferino Vaz, BR-13083865 Campinas, SP - Brazil

• Document type: Journal article
• Source: Neuroscience Letters; v. 729, JUN 11 2020.
• Web of Science Citations: 0

Abstract

Recently the voltage-gated sodium (Nav) channels began to be studied as possible targets for analgesic drugs. In addition, specific Nav 1.8 blockers are currently being used to treat some types of chronic pain pathologies such as neuropathies and fibromyalgia. Nav 1.8(+) fibers convey nociceptive information to brain structures belonging to the limbic system, which is involved in the pathophysiology of major depressive disorders. From this, using a model of chronic social defeat stress (SDS) and intrathecal injections of Nav 1.8 antisense, this study investigated the possible involvement of Nav 1.8(+) nociceptive fibers in SDS- induced hyperalgesia in C57/BL mice. Our results showed that SDS induced a depressive-like behavior of social avoidance and increased the sensitivity to mechanical (electronic von Frey test) and chemical (capsaicin test) nociceptive stimuli. We also showed that intrathecal injection of Nav 1.8 antisense reversed the SDS-induced hyperalgesia as demonstrated by both, mechanical and chemical nociceptive tests. We confirmed the antisense efficacy and specificity in a separate no-defeated cohort through real-time PCR, which showed a significant reduction of Nav 1.8 mRNA and no reduction of Nav 1.7 and Nav 1.9 in the L4, L5 and L6 dorsal root ganglia (DRG). The present study advances the understanding of SDS-induced hyperalgesia, which seems to be dependent on Nav 1.8(+) nociceptive fibers. (AU)

• FAPESP's process: 15/26777-7 - Study of preventive and therapeutic effects of physical exercise on hyperalgesia induced by social defeat stress in mice and associated neuroplastic mechanisms.
• Grantee: Cesar Renato Sartori
• Support Opportunities: Regular Research Grants