Nasal application of hsv encoding human preproenkephalin blocks craniofacial pain in a rat model of traumatic brain injury

ABSTRACT According to Centers for Disease Control and Prevention, each year, an estimated 1.7 million Americans sustain a traumatic brain injury (TBI), which frequently leads to chronic

craniofacial pain. In this study we examine a gene therapy approach to the treatment of post-TBI craniofacial neuropathic pain using nasal application of a herpes simplex virus (HSV)-based

vector expressing human proenkephalin (SHPE) to target the trigeminal ganglia. Mild TBI was induced in rats by the use of a modified fluid percussion model. Two days after mild TBI,

following the development of facial mechanical allodynia, animals received either an intranasal application of vehicle or recombinant HSV encoding human preproenkephalin or lacZ reporter

gene encoding control vector (SHZ.1). Compared with baseline response thresholds, mild TBI in SHZ.1 or vehicle-treated animals induced a robust craniofacial allodynia lasting at least 45

days. On the other hand, nasal SHPE application 2 days post-TBI attenuated facial allodynia, reaching significance by day 4–7 and maintaining this effect throughout the duration of the

experiment. Immunohistochemical examination revealed strong expression of human proenkephalin in trigeminal ganglia of SHPE, but not SHZ.1-treated rats. This study demonstrates that

intranasal administration of HSV-based gene vectors may be a viable, non-invasive means of treating chronic craniofacial pain, including post-TBI pain. Access through your institution Buy or

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references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA A C Meidahl,

 M Klukinov, A Z Tzabazis & D C Yeomans * Department of Neurosurgery, Aarhus University Hospital, Aarhus, Denmark A C Meidahl & J C Sorensen Authors * A C Meidahl View author

publications You can also search for this author inPubMed Google Scholar * M Klukinov View author publications You can also search for this author inPubMed Google Scholar * A Z Tzabazis View

author publications You can also search for this author inPubMed Google Scholar * J C Sorensen View author publications You can also search for this author inPubMed Google Scholar * D C

Yeomans View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to D C Yeomans. ETHICS DECLARATIONS COMPETING INTERESTS The

authors declare no conflict of interest. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Meidahl, A., Klukinov, M., Tzabazis, A. _et al._ Nasal

application of HSV encoding human preproenkephalin blocks craniofacial pain in a rat model of traumatic brain injury. _Gene Ther_ 24, 482–486 (2017). https://doi.org/10.1038/gt.2017.55

Download citation * Received: 15 November 2016 * Revised: 06 April 2017 * Accepted: 14 June 2017 * Published: 20 July 2017 * Issue Date: August 2017 * DOI: https://doi.org/10.1038/gt.2017.55

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