title: ARA 290 relieves pathophysiological pain by targeting TRPV1 channel: Integration between immune system and nociception.
abstract: ARA 290 is an erythropoietin-derived polypeptide that possesses analgesic and tissue protective effect in many diseases such as diabetes and cancer. The analgesic effect of ARA 290 is mediated by its anti-inflammatory and immunomodulatory functions, or more specifically, by targeting the innate repair receptor (IRR) to down-regulate inflammation to alleviate neuropathic pain. However, whether other mechanisms or pathways are involved in ARA 290-mediated analgesic effect remains elusive. In this study, we are particularly interested in whether ARA 290 could directly target peripheral nociceptors by blocking or influencing receptors in pain sensation. Using calcium imaging, cell culture and behavioral tests, we demonstrated that ARA 290 was able to specifically inhibit TRPV1 channel activity, and relieve the mechanical hypersensitivity induced by capsaicin. Our study suggested that ARA 290 could potentially function as a novel antagonist for TRPV1 channel. This finding would not only contribute to the development of new pain treatment using ARA 290, but also help to improve our understanding of the integration between the immune system and the peripheral nervous system.
authors.affiliation: Department of Anesthesiology, Provincial Hospital Affiliated to Shandong University, 324# Jingwu Road, Jinan 250021, Shandong, China.
authors.forename: Wenjia
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Center for Reproductive Medicine, Provincial Hospital Affiliated to Shandong University, 157# Jingliu Road, Jinan 250021, Shandong, China.
authors.forename: Guanling
authors.initials: G
authors.lastname: Yu
authors.affiliation: Department of Anesthesiology, Provincial Hospital Affiliated to Shandong University, 324# Jingwu Road, Jinan 250021, Shandong, China. Electronic address: myzhang324@sina.com.
authors.forename: Mengyuan
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D020013:Calcium Signaling; D002211:Capsaicin / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D059225:Nociception; D059226:Nociceptive Pain / Q000188:drug therapy* / Q000276:immunology; D009842:Oligopeptides / Q000494:pharmacology*; D050916:TRPV Cation Channels / Q000502:physiology*
chemical_list: D000700:Analgesics; D009842:Oligopeptides; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; C576178:cibinetide; D002211:Capsaicin
keywords: ARA 290; Inflammation; Neuropathic pain; Nociception; TRPV1