Analgesic Effects of Ephedra Herb Extract, Ephedrine Alkaloids–Free Ephedra Herb Extract, Ephedrine, and Pseudoephedrine on Formalin-Induced Pain

• Published in: Biological & pharmaceutical bulletin Vol. 42; no. 9; pp. 1538 - 1544
• Main Authors: Nakamori, Shunsuke, Takahashi, Jun, Hyuga, Sumiko, Yang, Jinwei, Takemoto, Hiroaki, Maruyama, Takuro, Oshima, Naohiro, Uchiyama, Nahoko, Amakura, Yoshiaki, Hyuga, Masashi, Hakamatsuka, Takashi, Goda, Yukihiro, Odaguchi, Hiroshi, Hanawa, Toshihiko, Kobayashi, Yoshinori
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.09.2019; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: Administration, Oral; Alkaloids; Analgesia; analgesic effect; Analgesics; Analgesics - isolation & purification; Analgesics - therapeutic use; Animals; Bans; Disease Models, Animal; Ephedra; Ephedra - chemistry; Ephedra Herb; Ephedrine; Ephedrine - therapeutic use; Formaldehyde; formalin test; Glucose; Herbs; Inflammation; Male; Mice, Inbred Strains; Oral administration; Pain; Pain - drug therapy; Pain Measurement; Pain perception; Plant Extracts - isolation & purification; Plant Extracts - therapeutic use; Pseudoephedrine - therapeutic use; Rotarod Performance Test; Time Factors; analgesic effect; ephedrine; pain; Ephedra Herb; formalin test
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b19-00260

The analgesic effect of Ephedra Herb (EH) is believed to be derived from the anti-inflammatory action of pseudoephedrine (Pse). We recently reported that ephedrine alkaloids–free EH extract (EFE) attenuates formalin-induced pain to the same level as that achieved by EH extract (EHE), which suggests that the analgesic effect of EH may not be due to ephedrine alkaloids (EAs). To examine the contribution of EAs to the analgesic effect of EH, mice were injected with formalin to induce a biphasic pain reaction (first phase, 0–5 min; second phase, 10–45 min) at various time points after oral administration of the following test drugs: ephedrine (Eph), Pse, “authentic” EHE from Tsumura & Co. (EHE-Ts), EFE, and EHE that was used as the source of EFE (EHE-To). Biphasic pain was suppressed at 30 min after administration of Eph, EHE-Ts, and EHE-To. At 6 h after administration of EFE, EHE-To, and Pse—and at 4 to 6 h after administration of EHE-Ts—only second-phase pain was suppressed; however, the effect of Pse at 6 h was not significant. These results suggested that EHE has a biphasic analgesic effect against biphasic formalin-induced pain: in the first phase of analgesia (30 min after administration), biphasic pain is suppressed by Eph; in the second phase of analgesia (4–6 h after administration), second-phase pain is alleviated by constituents other than EAs, although Pse may partially contribute to the relief of second-phase pain.