Selective deficiencies in descending inhibitory modulation in neuropathic rats: Implications for enhancing noradrenergic tone

Ryan Patel, Chaoling Qu, Jennifer Y. Xie, Frank Porreca, Anthony H. Dickenson

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Pontine noradrenergic neurones form part of a descending inhibitory system that influences spinal nociceptive processing. Weak or absent descending inhibition is a common feature of chronic pain patients. We examined the extent to which the descending noradrenergic system is tonically active, how control of spinal neuronal excitability is integrated into thalamic relays within sensorydiscriminative projection pathways, and how this inhibitory control is altered after nerve injury. In vivo electrophysiology was performed in anaesthetised spinal nerve ligated (SNL) and sham-operated rats to record from wide dynamic range neurones in the ventral posterolateral thalamus (VPL). In sham rats, spinal block of a2-Adrenoceptors with atipamezole resulted in enhanced stimulus-evoked and spontaneous firing in the VPL, and produced conditioned place avoidance. However, in SNL rats, these conditioned avoidance behaviours were absent. Furthermore, inhibitory control of evoked neuronal responses was lost, but spinal atipamezole markedly increased spontaneous firing. Augmenting spinal noradrenergic tone in neuropathic rats with reboxetine, a selective noradrenergic reuptake inhibitor, modestly reinstated inhibitory control of evoked responses in the VPL but had no effect on spontaneous firing. By contrast, clonidine, an a2 agonist, inhibited both evoked and spontaneous firing, and exhibited increased potency in SNL rats compared with sham controls. These data suggest descending noradrenergic inhibitory pathways are tonically active in sham rats. Moreover, in neuropathic states, descending inhibitory control is diminished, but not completely absent, and distinguishes between spontaneous and evoked neuronal activity. These observations may have implications for how analgesics targeting the noradrenergic systemprovide relief.

Original languageEnglish (US)
Pages (from-to)1887-1899
Number of pages13
Issue number9
StatePublished - Sep 1 2018


  • Conditioned place avoidance
  • Descending inhibition
  • In vivo electrophysiology
  • Neuropathic pain
  • Noradrenaline
  • Noradrenaline reuptake inhibitor
  • Spinal nerve ligation
  • Ventral posterolateral thalamus
  • a2-Adrenoceptor

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine


Dive into the research topics of 'Selective deficiencies in descending inhibitory modulation in neuropathic rats: Implications for enhancing noradrenergic tone'. Together they form a unique fingerprint.

Cite this