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Endogenous analgesic action of the pontospinal noradrenergic system spatially restricts and temporally delays the progression of neuropathic pain following tibial nerve injury

Research output: Contribution to journalArticle

Original languageEnglish
Article number3763373
Pages (from-to)1680-1690
Number of pages11
JournalPAIN
Volume154
Issue number9
Early online date14 May 2013
DOIs
DateE-pub ahead of print - 14 May 2013
DatePublished (current) - 1 Sep 2013

Abstract

Pontospinal noradrenergic neurons form part of an endogenous analgesic system that suppresses acute pain, but there is conflicting evidence about its role in neuropathic pain. We investigated the chronology of descending noradrenergic control during the development of a neuropathic pain phenotype in rats following tibial nerve transection (TNT). A lumbar intrathecal cannula was implanted at the time of nerve injury allowing administration of selective α-adrenoceptor (α-AR) antagonists to sequentially assay their effects upon the expression of allodynia and hyperalgesia. Following TNT animals progressively developed mechanical and cold allodynia (by day 10) and subsequently heat hypersensitivity (day 17). Blockade of α2-AR with intrathecal yohimbine (30 μg) revealed earlier ipsilateral sensitization of all modalities while prazosin (30 μg, α1-AR) was without effect. Established allodynia (by day 21) was partly reversed by the re-uptake inhibitor reboxetine (5 μg, i.t.) but yohimbine no longer had any sensitising effect. This loss of effect coincided with a reduction in the descending noradrenergic innervation of the ipsilateral lumbar dorsal horn. Yohimbine reversibly unmasked contralateral hindlimb allodynia and hyperalgesia of all modalities and increased dorsal horn c-fos expression to an innocuous brush stimulus. Contralateral thermal hyperalgesia was also reversibly uncovered by yohimbine administration in a contact heat ramp paradigm in anaesthetised TNT rats. Following TNT there is an engagement of inhibitory α2-AR- mediated noradrenergic tone which completely masks contralateral and transiently suppresses the development of ipsilateral sensitization. This endogenous analgesic system plays a key role in shaping the spatial and temporal expression of the neuropathic pain phenotype after nerve injury. © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Additional information

Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

    Research areas

  • Neuropathic pain, Complex regional pain syndrome, Descending control, Norepinephrine, DORSAL-HORN, SPINAL-CORD, DESCENDING CONTROL, HEAT NOCICEPTORS, RAT MODEL, PHARMACOLOGICAL CHARACTERIZATION, TACTILE HYPERSENSITIVITY, ELECTRICAL-STIMULATION, GENERAL-POPULATION, ANIMAL-MODEL

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