Reversal of neuropathic pain by HSV-1-mediated decrease of noradrenaline in a pain facilitatory area of the brain

• Type: Article in International Scientific Journal
• Date: 2010

Authors

Maria Isabel Martins (Author) FMUP; Costa Araujo, S (Author) Other; Fadel, J (Author) Other; Wilson, SP (Author) Other; Deolinda Lima (Author) FMUP; Isaura Tavares (Author) FMUP

Journal

Title: Pain

Vol. 151

Pages: 137-145

ISSN: 0304-3959

Publisher: Wolters Kluwer Health

Indexing

ISI Web of Knowledge - 34 Citations

Scopus - 35 Citations

Scientific classification

FOS: Natural sciences > Biological sciences

Other information

Authenticus ID: P-003-2MD

DOI: 10.1016/j.pain.2010.06.027

Abstract (EN): Descending modulation of nociceptive transmission depends on the release of noradrenaline at the spinal cord. The role of noradrenaline in the control of nociceptive transmission at the supraspinal pain control system remains understudied. As chronic pain is associated with enhanced descending facilitation of nociceptive transmission, we sought to determine the role of noradrenaline in pain facilitation from the brain during neuropathic pain. We determined the action of the noradrenergic input to the dorsal reticular nucleus (DRt), a unique pain facilitatory area, using the spared nerve injury model. Injections of the alpha 1-adrenoreceptor agonist phenylephrine into the DRt induced hyperalgesia and allodynia, indicating that alpha 1-adrenoreceptors enhance the facilitatory action of the nucleus. This led us to reduce noradrenaline release at the DRt using a viral vector derived from the Herpes Simplex virus type 1 (HSV-1) which carried the tyrosine hydroxylase (TH) transgene in antisense orientation. The reduction of noradrenaline release, confirmed by microdialysis experiments, induced a long-lasting attenuation of pain responses, which was reverted by the local administration of phenylephrine. The present study indicates that the noradrenergic modulation of a pronociceptive area at the supraspinal pain control system accounts for pain facilitation, through the activation of alpha 1-adrenoreceptors. The study also shows that sustained effects on chronic pain can be achieved by decreasing the release of noradrenaline in a pain facilitatory centre of the brain using gene transfer.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9