# Cannabigerol Modulates Cannabinoid Receptor Type 2 Expression in the Spinal Dorsal Horn and Attenuates Neuropathic Pain Models

## TL;DR

Cannabigerol (CBG) reduces chronic pain by modulating spinal CB2R and decreasing microglial activity in animal models.

## Contribution

This study identifies CBG's antinociceptive effects and its mechanism involving CB2R in chronic pain models.

## Key findings

- CBG reduced nociceptive responses in formalin and hot plate tests at 30 mg/kg.
- CBG attenuated thermal and mechanical hypersensitivity in spinal nerve ligated rats.
- CB2R signaling was crucial for CBG's effects, while CB1R, BDNF, and TNF were not major contributors.

## Abstract

Background/Objectives: The expanding focus on novel therapeutic pathways for long-term pain relief has directed interest toward compounds obtained from Cannabis sativa. This study evaluated the antinociceptive potential of cannabigerol-enriched extract (CBG) in models of acute and chronic hypernociception, along with morphological outcomes. Methods: Formalin and hot plate tests were used on male Swiss mice to assess acute oral antinociception. To the chronic pain model, 8-week-old male Wistar rats underwent spinal nerve ligation (SNL), and CBG was administered orally by gavage once daily for 14 days. Results: CBG reduced nociceptive responses in the formalin test and hot plate tests, mainly at a dose of 30 mg/kg, showing antinociceptive activity. CBG attenuated SNL-induced thermal and mechanical hypersensitivity, accompanied by reduced microglial density and spinal morphological changes. Importantly, cannabinoid receptor type 2 (CB2R) signaling contributed to the antinociceptive effects of orally administered CBG, whereas cannabinoid receptor type 1 (CB1R), Brain-Derived Neurotrophic Factor (BDNF), and Tumor Necrosis Factor (TNF) did not appear to play major roles under our experimental conditions. Conclusions: Collectively, these findings support CBG as a promising alternative for chronic pain management.