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Differential suppression of the ipsi- and contralateral nociceptive reflexes in the neonatal rat spinal cord by agonists of μ-, δ- and κ-opioid receptors
Univ Porto, Inst Invest & Inovacao Saude, Porto, Portugal;Univ Porto, Neuronal Networks Grp, IBMC, Rua Alfredo Allen 208, P-4200135 Porto, Portugal.
Univ Porto, Inst Invest & Inovacao Saude, Porto, Portugal;Univ Porto, Neuronal Networks Grp, IBMC, Rua Alfredo Allen 208, P-4200135 Porto, Portugal.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.ORCID iD: 0000-0002-1332-7067
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.ORCID iD: 0000-0002-2451-4386
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2019 (English)In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1717, p. 182-189Article in journal (Refereed) Published
Abstract [en]

Nociceptive discharges caused by the unilateral tissue damage are processed in the spinal cord by both ipsi- and contralateral neuronal circuits. The mechanisms of the neurotransmitter control of this bilateral excitation spread is poorly understood. Spinally administered opiates are known to suppress nociceptive transmission and nociceptive withdrawal reflexes. Here we investigated whether three major types of opioid receptors are involved in the bilateral control of the spinal nociceptive sensorimotor processing. Effects of the μ-, δ- and κ-opioid receptor agonists on the ipsi- and contralateral nociceptive reflexes were studied by recording slow ventral root potentials in an isolated spinal cord preparation of the new-born rat. Absolute levels of expression of the opioid genes were analyzed by the droplet digital PCR. Ipsi- and contralateral slow ventral root potentials were most strongly suppressed by the μ-opioid receptor agonist DAMGO, by 63% and 85%, followed by the κ-opioid receptor agonist U-50488H, by 44% and 73%, and δ-opioid receptor agonist leucine-enkephalin, by 27% and 49%, respectively. All these agonists suppressed stronger contra- than ipsilateral responses. Naloxone prevented effects of the agonists indicating that they act through opioid receptors, which, as we show, are expressed in the neonatal spinal cord at the levels similar to those in adults. Thus, opioid receptor agonists suppress the segmental nociceptive reflexes. Stronger contralateral effects suggest that the endogenous opioid system regulates sensorimotor processing in the spinal commissural pathways. These effects of opioids may be relevant for treatment of symmetric clinical pain symptoms caused by unilateral tissue injury.

Place, publisher, year, edition, pages
2019. Vol. 1717, p. 182-189
Keywords [en]
Spinal segmental reflexes, Nociception, Opioids, Primary afferents, Motoneurons
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:uu:diva-388750DOI: 10.1016/j.brainres.2019.04.026ISI: 000470799000020PubMedID: 31028728OAI: oai:DiVA.org:uu-388750DiVA, id: diva2:1342977
Funder
EU, Horizon 2020Swedish Research CouncilSwedish Institute
Note

De 2 sista författarna delar sistaförfattarskapet.

Available from: 2019-08-15 Created: 2019-08-15 Last updated: 2019-08-15Bibliographically approved

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Kononenko, OlgaSarkisyan, DaniilBakalkin, Georgy

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