Increased Noradrenergic Neurotransmission to a Pain Facilitatory Area of the Brain Is Implicated in Facilitation of Chronic Pain. (September 2015)

• Record Type: Journal Article
• Authors: Martins, Isabel; Carvalho, Paulina; de Vries, Martin G.; Teixeira-Pinto, Armando; Wilson, Steven P.; Westerink, Ben H. C.; Tavares, Isaura
• Is Part Of: Anesthesiology. Volume 123:Number 3(2015)
• Publication Date: 2015-09
• Subjects: Anesthesiology -- Periodicals; Anesthetics -- Periodicals; Anesthesia -- Periodicals; 617.9605
• DOI: 10.1097/ALN.0000000000000749
• Languages: English
• ISSNs: 0003-3022

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Background:</title> <p>Noradrenaline reuptake inhibitors are known to produce analgesia through a spinal action but they also act in the brain. However, the action of noradrenaline on supraspinal pain control regions is understudied. The authors addressed the noradrenergic modulation of the dorsal reticular nucleus (DRt), a medullary pronociceptive area, in the spared nerve injury (SNI) model of neuropathic pain.</p> </sec> <sec> <title>Methods:</title> <p>The expression of the phosphorylated cAMP response element-binding protein (pCREB), a marker of neuronal activation, was evaluated in the locus coeruleus and A<sub>5</sub> noradrenergic neurons (n = 6 rats/group). pCREB was studied in noradrenergic DRt-projecting neurons retrogradely labeled in SNI animals (n = 3). <italic>In vivo</italic> microdialysis was used to measure noradrenaline release in the DRt on nociceptive stimulation or after DRt infusion of clonidine (n = 5 to 6 per group). Pharmacology, immunohistochemistry, and western blot were used to study α-adrenoreceptors in the DRt (n = 4 to 6 per group).</p> </sec> <sec> <title>Results:</title> <p>pCREB expression significantly increased in the locus coeruleus and A<sub>5</sub> of SNI animals, and most noradrenergic DRt-projecting neurons expressed pCREB. In SNI animals, noradrenaline levels significantly increased on pinprick (mean ± SD, 126 ± 14%; <italic>P</italic> = 0.025 <italic>vs.</italic> baseline) and acetone stimulation (mean ± SD, 151 ± 12%; <italic>P</italic> < 0.001 <italic>vs.</italic> baseline), and clonidine infusion showed decreased α<sub>2</sub>-mediated inhibitory function. α<sub>1</sub>-adrenoreceptor blockade decreased nociceptive behavioral responses in SNI animals. α<sub>2</sub>-adrenoreceptor expression was not altered.</p> </sec> <sec> <title>Conclusions:</title> <p>Chronic pain induces brainstem noradrenergic activation that enhances descending facilitation from the DRt. This suggests that antidepressants inhibiting noradrenaline reuptake may enhance pain facilitation from the brain, counteracting their analgesic effects at the spinal cord.</p> </sec> </abstract>