Details

Autor(en) / Beteiligte

• Zhu, Bin
• Gong, Nian
• Fan, Hui
• Peng, Chong-Sheng
• Ding, Xiu-Juan
• Jiang, Yi
• Wang, Yong-Xiang

Titel

Lamiophlomis rotata, an Orally Available Tibetan Herbal Painkiller, Specifically Reduces Pain Hypersensitivity States through the Activation of Spinal Glucagon-like Peptide-1 Receptors

Ist Teil von

• Anesthesiology (Philadelphia), 2014-10, Vol.121 (4), p.835-851

Ort / Verlag

United States: American Society of Anesthesiologists, Inc

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• BACKGROUND:Lamiophlomis rotata is an orally available Tibetan herb prescribed for the management of pain, with shanzhiside methylester (SM) and 8-O-acetyl-SM as quality control ingredients. This study aimed to evaluate the antinociceptive properties of L. rotata, determine whether SM and 8-O-acetyl-SM are principle effective ingredients, and explore whether L. rotata produces antinociception through activation of spinal glucagon-like peptide-1 receptors (GLP-1Rs). METHODS:Formalin test, neuropathic pain, and bone cancer pain models were used, and the animal sample size was 5 to 6 in each group. Hydrogen peroxide–induced oxidative damage was also assayed. RESULTS:The L. rotata aqueous extract blocked formalin-induced tonic hyperalgesia and peripheral nerve injury– and bone cancer–induced mechanical allodynia by 50 to 80%, with half-effective doses of 130 to 250 mg/kg, close to the human dosage. The herb was not effective in alleviating acute nociceptive pain. A 7-day gavage with L. rotata aqueous extract did not lead to antiallodynic tolerance. Total iridoid glycosides, rather than total flavonoids, were identified by the activity-tracking method as effective ingredients for antihyperalgesia, whereas both SM and 8-O-acetyl-SM were principal components. Further demonstrations using the GLP-1R antagonist and gene silencer against GLP-1R at both the spinal and the cellular levels indicated that L. rotata inhibited pain hyperactivity by activation of spinal GLP-1Rs, and SM and 8-O-acetyl-SM appeared to be orthosteric, reversible, and fully intrinsic agonists of both rat and human GLP-1Rs. CONCLUSIONS:Results support the notion that the activation of spinal GLP-1Rs leads to specific antinociception in pain hypersensitivity and further suggest that GLP-1R is a human-validated target molecule for the treatment of chronic pain.