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Characterization of spinal alpha-adrenergic modulation of nociceptive transmission and hyperalgesia throughout postnatal development in rats

Walker, SM; Fitzgerald, M; (2007) Characterization of spinal alpha-adrenergic modulation of nociceptive transmission and hyperalgesia throughout postnatal development in rats. BRIT J PHARMACOL , 151 (8) 1334 - 1342. 10.1038/sj.bjp.0707290. Gold open access

Abstract

Background and purpose: The selective alpha(2)-adrenergic agonist dexmedetomidine is used clinically for analgesia and sedation, but effects in early life are not well characterized. Investigation of age-related effects of dexmedetomidine is important for evaluating responses to exogenously administered analgesics and provides insight into postnatal function of noradrenergic pathways.Experimental Approach: We examined effects of epidural dexmedetomidine in anaesthetized rat pups (3, 10 and 21 postnatal days) using a quantitative model of nociception and C-fibre induced hyperalgesia. Electromyographic recordings of withdrawal responses to hindpaw mechanical stimuli measured effects of dexmedetomidine upon the baseline reflex and the response to mustard oil application on the hindpaw (primary hyperalgesia) or hindlimb (secondary hyperalgesia). In addition, we compared epidural with systemic administration, examined effects of spinal transection and evaluated heart rate changes following dexmedetomidine.Key Results: Epidural dexmedetomidine dose-dependently prevented mustard oil-induced hyperalgesia at all ages but dose requirements were lower in the youngest pups. Higher doses also suppressed the baseline nociceptive reflex when given epidurally, but had no effect when given systemically. Analgesic efficacy was the same for primary and secondary hyperalgesia, and was not diminished by spinal cord transection.Conclusions and Implications: Our laboratory studies predict that spinally mediated alpha(2)-agonist analgesia would be effective throughout postnatal development, dose requirements would be lower in early life and selective anti-hyperalgesic effects could be achieved with epidural administration at doses lower than associated with antinociceptive or cardiovascular effects. Clinical trials of alpha(2) agonists in neonates and infants should consider developmentally regulated changes.

Type: Article
Title: Characterization of spinal alpha-adrenergic modulation of nociceptive transmission and hyperalgesia throughout postnatal development in rats
Open access status: An open access publication
DOI: 10.1038/sj.bjp.0707290
Publisher version: http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC21898...
Keywords: dexmedetomidine, alpha(2)-adrenergic agonist, postnatal development, primary hyperalgesia, epidural, DORSAL-HORN, NEONATAL-RAT, DEXMEDETOMIDINE PHARMACODYNAMICS, ALPHA(2)-ADRENOCEPTOR AGONISTS, SYNAPTIC-TRANSMISSION, HEALTHY-VOLUNTEERS, RECEPTOR SUBTYPES, NMDA RECEPTOR, CORD, CHILDREN
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health > ICH Developmental Neurosciences Prog
URI: http://discovery.ucl.ac.uk/id/eprint/8855
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