Event Abstract

“The descending noradrenergic spinal modulation is impaired during prolonged joint inflammatory pain conditions.”

  • 1 Faculty of Medicine, University of Porto, Portugal
  • 2 i3S, Instituto de Investigação e Inovação em Saúde, Portugal

Chronic pain is a widespread condition responsible for a huge socioeconomic negative impact. Several monoaminergic systems, such as the noradrenergic system, are involved in descending modulation of pain (DMP) events, either through noxious stimuli facilitation or inhibition. Even though this is known, the pharmacologic approaches to treat severe chronic joint inflammatory pain (CJIP) are still mostly unsuccessful. To study the changes on descending noradrenergic pain modulation caused by CJIP, we performed spinal pharmacological studies, evaluated the expression levels of dopamine β-hydroxylase (DBH), the noradrenaline biosynthetic enzyme, and of the α2-adrenoreceptor (AR), and quantified the noradrenaline (NE) levels at the spinal cord of monoarthritic (MA) animals. MA was induced in adult male Wistar rats by complete Freund’s adjuvant injection (CFA) in the tibiotarsal joint. Control animals were injected with CFA vehicle. Movement-induced allodynia (ankle-bend test), mechanical hyperalgesia (Randall Selitto test) and signs of inflammation (inflammation score) were weekly evaluated in all animals during 6 weeks post-intraarticular injection. For the pharmacological studies (week 5), an intrathecal catheter was implanted above the L4-L5 spinal segments and one week later (week 6) cumulative doses (1, 5, 10µg) of clonidine, an α2-AR agonist, or saline were injected through the catheter. The effects of each dose were evaluated by the Randall Selitto test. DBH and α-2AR expression and NE levels were evaluated at L4 and 5 segments by immunohistochemistry and HPLC, respectively. MA animals showed typical movement-induced allodynia and mechanical hyperalgesia during the 6 weeks when compared to controls. Clonidine induced anti-hyperalgesia in MA animals, more significant at the highest dose, and produced no effects in controls. On MA rats, DBH labeling was significantly increased, no differences were found in α2-AR expression and NE spinal levels were lower, in comparison to controls In conclusion, chronic MA causes a loss of NE spinal input, triggered by the ongoing nociceptive input. However, a compensatory antinociceptive noradrenergic spinal mechanism to counteract this condition appears to be also developing, as indicated by DBH increase. Therapeutic strategies aiming at strengthening these antinociceptive noradrenergic spinal effects could represent new avenues when treating CJIP.

Acknowledgements

This work would not have been possible without the financial support of 2014–2020 North Portugal Regional Operational Programme.

Keywords: monoarthritis, Noradrenalin (NA), descending modulation, Spinal Cord, nociception and pain

Conference: XVI Meeting of the Portuguese Society for Neuroscience (SPN2019), Lisboa, Portugal, 30 May - 1 Jun, 2019.

Presentation Type: Oral presentation

Topic: Sensory Processing

Citation: Pereira Da Silva R, Da Costa Pereira J, Alonso R, Martins I and Neto F (2019). “The descending noradrenergic spinal modulation is impaired during prolonged joint inflammatory pain conditions.”. Front. Cell. Neurosci. Conference Abstract: XVI Meeting of the Portuguese Society for Neuroscience (SPN2019). doi: 10.3389/conf.fncel.2019.01.00033

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Received: 21 Feb 2019; Published Online: 26 Apr 2019.

* Correspondence: Dr. Raquel Pereira Da Silva, Faculty of Medicine, University of Porto, Porto, Portugal, raquel.silva.farm.86@gmail.com

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