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

ConclusionCitral is an effective analgesic in an arthritic pain model by increasing spinal 5-HT signaling and reducing spinal SAPK/JNK phosphorylation and systemic oxidative stress.Graphical abstractNeurochemical mechanisms involved in citral-induced analgesia in arthritis. (A) Complete Freund's adjuvant (CFA)-induced arthritis reduces spinal serotonin metabolism in the lumbar dorsal horn of the spinal cord ipsilateral to the injured joint, as indicated by the reduction in the spinal levels of the main metabolite of serotonin (5-HT), 5-hydroxyindole-3-acetic acid (5-HIAA). Moreover, there is a reduction in glycogen synthase kinase-3β (GSK3β) phosphorylation, which is a 5-HT-regulated intracellular protein, and an increase in stress-activated protein kinase (SAPK)/jun N-terminal kinase (JNK) phosphorylation. Systemically, arthritis increases plasma superoxide dismutase levels, which indicate an increase in plasma reactive oxygen species (ROS). Together, the alteration of the molecules described and certainly many other aspects contribute to a scenario of increased central sensitization and chronic arthritic pain. (B) During arthritis, chronic treatment with citral increases spinal 5-HT and regulates spinal 5-HT metabolism (i.e., 5-HIAA levels), prevents CFA-induced increase in spinal GSK3β phosphorylation and reduces CFA-induced increase in SAPK/JNK phosphorylation, and reduces plasma ROS. Here, we propose that the increase in 5-HT signaling in the spinal cord combined with...
Source: Journal of Ethnopharmacology - Category: Drugs & Pharmacology Source Type: research