Electrophysiological correlates of hyperalgesic priming in vitro and in vivo

Pain. 2013 Oct;154(10):2207-2215. doi: 10.1016/j.pain.2013.07.004. Epub 2013 Jul 4.

Abstract

We have modeled the transition from acute to chronic pain in the rat. In this model (termed hyperalgesic priming) a chronic state develops after a prior inflammatory process or exposure to an inflammatory mediator, in which response to subsequent exposure to prostaglandin E2 (PGE2) is characterized by a protein kinase Cε-dependent marked prolongation of mechanical hyperalgesia. To assess the effect of priming on the function of the nociceptor, we have performed in vitro patch clamp and in vivo single-fiber electrophysiology studies using tumor necrosis factor α to induce priming. In vitro, the only change observed in nociceptors cultured from primed animals was a marked hyperpolarization in resting membrane potential (RMP); prolonged sensitization, measured at 60 minutes, could not be tested in vitro. However, complimentary with behavioral findings, in vivo baseline mechanical nociceptive threshold was significantly elevated compared to controls. Thirty minutes after injection of PGE2 into the peripheral receptive field, both primed and control nociceptors showed enhanced response to mechanical stimulation. However, 60 minutes after PGE2 administration, the response to mechanical stimulation was further increased in primed but not in control nociceptors. Thus, at the level of the primary afferent nociceptor, it is possible to demonstrate both altered function at baseline and prolonged PGE2-induced sensitization. Intrathecal antisense (AS) to Kv7.2, which contributes to RMP in sensory neurons, reversibly prevented the expression of priming in both behavioral and single-fiber electrophysiology experiments, implicating these channels in the expression of hyperalgesic priming.

Keywords: Action potential; Hyperalgesia; KCNQ; Nociceptor; Pain; Prostaglandin E(2); Resting membrane potential; Tumor necrosis factor alpha.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Cells, Cultured
  • Electrophysiological Phenomena / physiology
  • Gene Knockdown Techniques / methods
  • Hyperalgesia / diagnosis*
  • Hyperalgesia / physiopathology*
  • Male
  • Membrane Potentials / physiology
  • Rats
  • Rats, Sprague-Dawley