The Potential Antinociceptive Effect and Mechanism of Cannabis sativa L. Extract on Paclitaxel-Induced Neuropathic Pain in Rats Uncovered by Multi-Omics Analysis

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“Cannabis sativa L. (hemp) is a herbaceous plant rich in cannabinoids with a long history of use in pain treatment.

The most well-characterized cannabinoids, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC), garnered much attention in chemotherapy-induced peripheral neuropathy (CIPN) treatment. However, few studies have investigated the biological benefits and mechanism of hemp extract on CIPN.

In the present study, hemp extract (JG) rich in cannabinoids was extracted by supercritical fluid carbon dioxide extraction (SFCE). The antinociceptive efficacy was evaluated using a paclitaxel-induced peripheral neuropathy (PIPN) rat model based on behavioral tests. Further omics-based approaches were applied to explore the potential mechanisms.

The results showed that JG decreased mechanical allodynia, thermal hyperalgesia, and inflammatory cytokines in PIPN rats significantly. Transcriptome analysis identified seven key genes significantly regulated by JG in PIPN model rats, mainly related to the neuroactive ligand-receptor interaction pathway, PPAR signaling pathway, and cAMP signaling pathway. In metabolomic analysis, a total of 39 significantly altered metabolites were identified, mainly correlated with pentose and glucuronate interconversions and the glycerophospholipid metabolism pathway.

Gut microbiota analysis suggested that increased community Lachnoclostridium and Lachnospiraceae_UCG-006 in PIPN rats can be reversed significantly by JG.

In conclusion, hemp extract exhibited antinociceptive effects on PIPN. The analgesic mechanism was probably related to the regulation of inflammation, neuroactive ligand-receptor interaction pathway, sphingolipid metabolism, etc. This study provides novel insights into the functional interactions of Cannabis sativa L. extract on PIPN.”

“In conclusion, the antinociceptive effects and mechanism of Cannabis sativa L. extract rich in cannabinoids in PIPN rats were evaluated by using pharmacological methods integrated with transcriptomic analysis, metabolomic analysis, and gut microbiota analysis. 

Cannabis sativa L. extract effectively alleviated neuropathic pain induced by PTX, mainly by the identified 7 key genes, 39 metabolic biomarkers, and 2 bacterial genera.

Related pathways may be involved in the inflammatory response, regulating neuroactive ligand–receptor interaction pathway, PPAR signaling pathway, inflammatory mediator regulation of TRP channels, glycerophospholipid metabolism, pentose and glucuronate interconversions, etc.

Our study provides novel insights into the functional interactions of Cannabis sativa L. extract on PIPN, which offers key information for new strategies in PIPN treatment and provides a reference for the medicinal development of hemp.”

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