Treatment of chronic pain by designer cells controlled by spearmint aromatherapy.

Abstract	Current treatment options for chronic pain are often associated with dose-limiting toxicities, or lead to drug tolerance or addiction. Here, we describe a pain management strategy, based on cell-engineering principles and inspired by synthetic biology, consisting of microencapsulated human designer cells that produce huwentoxin-IV (a safe and potent analgesic peptide that selectively inhibits the pain-triggering voltage-gated sodium channel NaV1.7) in response to volatile spearmint aroma and in a dose-dependent manner. Spearmint sensitivity was achieved by ectopic expression of the R-carvone-responsive olfactory receptor OR1A1 rewired via an artificial G-protein deflector to induce the expression of a secretion-engineered and stabilized huwentoxin-IV variant. In a model of chronic inflammatory and neuropathic pain, mice bearing the designer cells showed reduced pain-associated behaviour on oral intake or inhalation-based intake of spearmint essential oil, and absence of cardiovascular, immunogenic and behavioural side effects. Our proof-of-principle findings indicate that therapies based on engineered cells can achieve robust, tunable and on-demand analgesia for the long-term management of chronic pain.
Authors	Hui Wang, Mingqi Xie, Ghislaine Charpin-El Hamri, Haifeng Ye, Martin Fussenegger
Journal	Nature biomedical engineering (Nat Biomed Eng) Vol. 2 Issue 2 Pg. 114-123 (02 2018) ISSN: 2157-846X [Electronic] England
PMID	31015627 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	NAV1.7 Voltage-Gated Sodium Channel Oils, Volatile Spider Venoms Volatile Organic Compounds huwentoxin IV, Selenocosmia huwena Formaldehyde
Topics	Animals Aromatherapy Female Formaldehyde (toxicity) HEK293 Cells Humans Mentha spicata (chemistry, metabolism) Mice Mice, Inbred C57BL NAV1.7 Voltage-Gated Sodium Channel (genetics, metabolism) Neuralgia (chemically induced, metabolism, therapy) Odorants Oils, Volatile (chemistry) Pain Threshold Prostheses and Implants Sonication Spider Venoms (genetics, metabolism, toxicity) Volatile Organic Compounds (chemistry, therapeutic use)

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