title: Effect of toad skin extracts on the pain behavior of cancer model mice and its peripheral mechanism of action.
abstract: The changes in thermal and mechanical hyperalgesia in paw cancer pain model mice and the action mechanism of toad skin extracts (TSE) was investigated. Eighty female mice were subcutaneously injected with saline or inoculated with H22 hepatoma cells in the right hind paw and administration with saline, vehicle, morphine and TSE. The pain behavior was recorded before treatment and at 0.5, 1.0, 1.5, 3 and 6h after initial administration, and thereafter on the 2nd, 4th, 6th, and 8th day after administration. On the last day, samples were collected after the euthanasia for the detection of β-END, CRF, IL-1β, POMC, μ-OR, CD3+, CD8+ and CD4+ in sera and the tumor tissues. The results showed that TSE significantly increased the thresholds of thermal pain and mechanical pain, and upregulated the expressions of β-END, CRF, POMC, CD3+, CD8+ and μ-OR, and downregulated the expression of CD4+. These results indicate that TSE significantly relieved pain in cancer pain model mice and raised their pain threshold. In addition, TSE seems to play a prominent role in promoting the activity of tumor infiltrating lymphocytes (TILs, CD3+ and CD8+ T cells), and this immune-cell-derived peripheral analgesic pathway might have widespread potential for clinical use.
authors.affiliation: College of Medical Science, China Three Gorges University, Yichang 443002, Hubei, China; Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, Yichang 443002, Hubei, China. Electronic address: chentao@ctgu.edu.cn.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.affiliation: College of Medical Science, China Three Gorges University, Yichang 443002, Hubei, China.
authors.forename: Shen-Jun
authors.initials: SJ
authors.lastname: Yuan
authors.affiliation: Hubei Institute Co., Ltd.. of Pharmaceutical Industry, Wuhan 430061, Hubei, China.
authors.forename: Xue-Qin
authors.initials: XQ
authors.lastname: Yu
authors.affiliation: The Second Hospital of Yichang, Yichang 443000, Hubei, China.
authors.forename: Liang-Bo
authors.initials: LB
authors.lastname: Jiao
authors.affiliation: College of Medical Science, China Three Gorges University, Yichang 443002, Hubei, China; Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, Yichang 443002, Hubei, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.affiliation: College of Medical Science, China Three Gorges University, Yichang 443002, Hubei, China.
authors.forename: Wang-Long
authors.initials: WL
authors.lastname: Chen
authors.affiliation: College of Medical Science, China Three Gorges University, Yichang 443002, Hubei, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xie
mesh_terms: D000818:Animals; D001001:Anura / Q000502:physiology*; D016827:CD8 Antigens / Q000378:metabolism; D002457:Cell Extracts / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000628:therapy*; D008114:Liver Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D008213:Lymphocyte Activation / Q000187:drug effects; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D059408:Pain Management; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D012867:Skin / Q000166:cytology*; D012878:Skin Neoplasms / Q000473:pathology / Q000628:therapy*
chemical_list: D016827:CD8 Antigens; D002457:Cell Extracts
keywords: Analgesic; Cancer pain; Toad skin extracts; Tumor infiltrating lymphocytes; β-endorphin; μ-opioid receptor