Inflammatory pain reduces C fibre activity-dependent slowing in a sex dependent manner, amplifying nociceptive input to the spinal cord

Allen C. Dickie, Barry McCormick, Veny Lukito, Kirsten L. Wilson, Carole Torsney*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

C fibres display activity-dependent slowing (ADS), whereby repetitive stimulation (≥1Hz) results in a progressive slowing of action potential conduction velocity, which manifests as a progressive increase in response latency. However, the impact of ADS upon spinal pain processing has not been explored nor whether ADS is altered in inflammatory pain conditions. To investigate, compound action potentials were made, from dorsal roots isolated from rats with or without complete Freund's adjuvant (CFA) hindpaw inflammation, in response to electrical stimulus trains. CFA inflammation significantly reduced C fibre ADS at 1 and 2Hz stimulation rates. Whole-cell patch-clamp recordings in the spinal cord slice preparation with attached dorsal roots, also demonstrated that CFA inflammation reduced ADS in the monosynaptic C fibre input to lamina I neurokinin 1 receptor expressing neurons (1-10Hz stimulus trains) without altering the incidence of synaptic response failures. When analysed by sex it was revealed that females display a more pronounced ADS that is reduced by CFA inflammation to a level comparable with males. Cumulative ventral root potentials evoked by long and short dorsal root stimulation lengths, to maximise and minimise the impact of ADS, respectively, demonstrated that reducing ADS facilitates spinal summation and this was also sex-dependent. This finding correlated with the behavioural observation of increased noxious thermal thresholds and enhanced inflammatory thermal hypersensitivity in females. We propose that sex/inflammation dependent regulation of C fibre ADS can, by controlling the temporal relay of nociceptive inputs influence the spinal summation of nociceptive signals contributing to sex/inflammation dependent differences in pain sensitivity.
Original languageEnglish
Pages (from-to)6488-6502
Number of pages15
JournalJournal of Neuroscience
Volume37
Issue number27
Early online date2 Jun 2017
DOIs
Publication statusPublished - 5 Jul 2017

Keywords

  • conduction velocity slowing
  • dorsal horn
  • hyperalgesia
  • nociceptor
  • primary afferent
  • spinal output neurons
  • PRIMARY AFFERENT NEURONS
  • CURRENT I-H
  • RECEPTOR-EXPRESSING NEURONS
  • PRIMARY SENSORY NEURONS
  • SODIUM-CHANNEL BLOCKER
  • SUBSTANCE-P RECEPTOR
  • LAMINA-I
  • CONDUCTION-VELOCITY
  • DORSAL-HORN
  • NEUROPATHIC PAIN

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