Is citral able to modulate nociception in obese mice?

• Grant number: 23/13172-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: February 01, 2024
• End date: February 28, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Ethnopharmacology
• Principal Investigator: Clélia Akiko Hiruma Lima
• Grantee: Felipe Lima Dario
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Obesity is a prevalent chronic disease and has been described as being highly correlated with pain, profoundly interfering with the quality of life of patients. Preclinical models have shown hyperalgesia in rodents fed a high-fat diet (HFD). Obesity also increases the intensity of neuropathic pain, a dysfunctional, prevalent, and disabling pain with no specific effective treatments and no adverse effects. Citral is a monoterpene used by the food and cosmetics industry with proven anti-inflammatory and antinociceptive effects; however, it is not known how it affects nociception in the presence of obesity. This study aims to characterize the effects of citral on nociception in obese male C57BL/6J mice and to investigate the mechanisms of action involved. To this end, the animals will be fed a standard diet and an HFD (15% and 60% of calories from lipids, respectively) for at least 12 weeks. They will then be subjected to formalin and hot plate tests to assess their state of nociception and the effect of citral (100 and 300 mg/kg p.o.). Tests with 5-HT2A, GABAA, and TLR4 antagonists will then be performed to identify citral's mechanisms of action during obesity. In addition, the animals will be subjected to paw ischemia and reperfusion to induce neuropathic pain, characterized by allodynia. The mechanical sensitivity of these animals will be measured using the von Frey test. 5-HT, CGRP, GABA, AdipoR1, Ob-Rb, TLR4, and the phosphorylation of the MAPKs ERK1/2, JNK, and p38, markers associated with nociceptive signaling and its modulation in the spinal cord, will be quantified. Serum levels of leptin and adiponectin will also be determined, in addition to evaluating the M1/M2 polarization of microglia. Data will be expressed as mean ± SEM and values will be submitted to two-way ANOVA, followed by the Bonferroni and Tukey tests, with p<0.05. Given the information presented, citral has excellent potential to be studied in the modulation of neuropathic pain in the face of obesity and is expected to act by polarizing the microglia towards the M2 phenotype, in the control of descending inhibitory pain pathways and in TLR4 signaling.