Preventive and therapeutic effects of ephedrine alkaloids-free Ephedra Herb extract on paclitaxel-induced neuropathic pain

Currently, there are no effective prophylactic or therapeutic drugs for the treatment of paclitaxel (PTX)-induced peripheral neuropathic pain (PTX-PNP), highlighting the urgent need for the development of effective prophylactic and therapeutic drugs. In this study, we initially compared the efficacy of Ephedra Herb extract (EHE) with that of ephedrine alkaloids-free Ephedra Herb extract (EFE), which lacked ephedrine alkaloids (EAs)-associated side effects, against the onset of PTX-induced mechanical allodynia, thermal hyperalgesia, and cold allodynia in mice. EHE and EFE demonstrated comparable preventive effects on the PTX-PNP in a dose-dependent manner. These results indicated that the preventive properties of EHE were independent of the EAs. Since elderly people are overwhelmingly more susceptible to developing cancer, we considered that EFE has greater benefits than EHE, so we conducted a study focused on the effects of EFE. EFE showed dose-dependent preventive effects on the onset of PTX-PNP. As a result of detailed investigation, coadministration of PTX and EFE (Co-EFE) was more effective than preadministration of EFE alone (Pre-EFE). And the effects of Co-EFE was same with the effect of preadministration of EFE and then coadministration of PTX and EFE (P&C-EFE). Additionally, Co-EFE after the onset of PTX-PNP improved PTX-induced mechanical allodynia, thermal hyperalgesia, and cold allodynia, confirming the therapeutic efficacy of EFE on PTX-PNP. In contrast, goshajinkigan, a Kampo medicine, and diclofenac, a non-steroidal anti-inflammatory drug, showed minimal therapeutic effects on PTX-PNP. These findings demonstrate the significant potential of EFE as a novel, safe prophylactic and therapeutic agent against PTX-PNP.