Geniposide Alleviates Neuropathic Pain in CCI Rats by Inhibiting the EGFR/PI3K/AKT Pathway And Ca2+ Channels.

Neuropathic pain (NP) is a common disorder among individuals worldwide, but there is still no effective treatment for NP. The EGFR pathway promotes NP nociceptive sensitization and represents a potential therapeutic target. Geniposide is abundant in natural plants and has various pharmacological activities, such as analgesia and anti-inflammation properties, which can improve NP, but the specific mechanisms have not been elucidated. The present study first predicted and molecularly docked geniposide targets, suggesting that geniposide may play a role in improving NP by targeting EGFR. This study further clarified that geniposide alleviates NP and improves the inflammatory response using a chronic constriction injury (CCI) model, whereas the administration of an EGFR agonist weakens the above effects of geniposide. Analysis of transcriptome data further suggests that geniposide not only improves CCI symptoms by reducing EGFR/PI3K/AKT pathway activity but also may exert anti-inflammatory effects by inhibiting the Ca2+ signaling pathway. The above results affirm the potential value of geniposide in the treatment of NP and lay the foundation for further clinical application.