Citral-induced analgesia is associated with increased spinal serotonin, reduced spinal nociceptive signaling, and reduced systemic oxidative stress in arthritis

Author(s)

Mota, Clarissa M. D. ^[1] ; Rodrigues-Santos, Caroline ^[2] ; Carolino, Ruither O. G. ^[2] ; Anselmo-Franci, Janete A. ^[2] ; Branco, Luiz G. S. ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Physiol, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Sch Dent Ribeirao Preto, Dept Morphol Physiol & Basic Pathol, Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Journal of Ethnopharmacology; v. 250, MAR 25 2020.
• Web of Science Citations: 1

Abstract

Ethnopharmacological relevance: Citral (3,7-dimethyl-2,6-octadienal) is the main component of Cymbopogon citrates (DC) Stapf, an herb with analgesic properties. Arthritic pain is the main unpleasant component of rheumatoid arthritis. The pharmacological approaches used to treat arthritic pain are often accompanied by adjuvant drugs or non-pharmacological treatments, showing a constant need in identifying new efficient analgesic drugs. Aim of the study: To test the hypothesis that citral, which is a monoterpenoid compound with therapeutic properties, reduces nociception, spinal pro-nociceptive and pro-inflammatory signaling, and systemic oxidative stress in arthritic rats. Materials and methods: Complete Freund's adjuvant (CFA) was administrated in the left knee joint of rats. Oral treatment with citral was performed during eight days and mechanical allodynia was monitored during the period of treatment to evaluate the analgesic effect of citral. We assessed the levels of serotonin (5-hydroxytryptamine, 5-HT) in the lumbar dorsal horn of the spinal cord (DHSC) and the profiles of expression of the glycogen synthase kinase-3 beta (GSK3 beta), which is a 5-HT-regulated intracellular protein, and of the stress-activated protein kinase (SAPK)/jun N-terminal kinase (JNK) in the Dl-ISC. Plasma levels of superoxide dismutase (SOD) were assessed as an indicator of oxidative stress. Results: Administration of CFA induced mechanical allodynia associated with reduced spinal GSK3P phosphorylation, increased spinal SAPK/JNK phosphorylation, and increased plasma SOD levels. Oral administration of citral reversed mechanical allodynia, increased endogenous spinal 5-HT levels, reduced spinal SAPK/JNK phosphorylation, and reduced plasma SOD levels. Conclusion: Citral shows anti-nociceptive effects in an animal model of arthritic pain by modulating spinal nociceptive signaling. (AU)

• FAPESP's process: 17/04644-0 - The role of central serotonin modulating mechanical and thermal nociception during systemic inflammation
• Grantee: Caroline Rodrigues dos Santos
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 16/17681-9 - Pathophysiological changes during systemic inflammation
• Grantee: Luiz Guilherme de Siqueira Branco
• Support Opportunities: Research Projects - Thematic Grants