Persistent cardiovascular and behavioral nociceptive responses to subcutaneous formalin require peripheral nerve input

Bradley K. Taylor, M. Alex Peterson, Allan I. Basbaum

Research output: Contribution to journalArticle

129 Scopus citations

Abstract

Hindpaw injection of formalin produces acute (Phase 1) and persistent (Phase 2) nociceptive behaviors. This model has provided critical evidence supporting a contribution of central sensitization (hyperexcitability of spinal neurons) to the expression of persistent pain. Here, we evaluated the contribution of ongoing peripheral nerve inputs to Phase 2 pain responses. In addition to pain behavior (flinching), we measured formalin-evoked increases in arterial pressure and heart rate; these cardiovascular responses were also biphasic in nature. The arterial pressure response correlated highly with behavior, and was dependent on formalin concentration (0.625-5.0%), indicating that it was largely driven by noxious input. Lightly anesthetized (0.7% halothane) rats exhibited robust increases in blood pressure in the absence of pain behavior, indicating cardiovascular responses did not reflect somatomotor-cardiovascular coupling. Animals obtained from Charles River exhibited slightly larger Phase 2 flinching and heart rate responses compared to those obtained from Bantin and Kingman, suggesting cardiovascular-related pain responses can vary with the source of animal. We next evaluated the contribution of ongoing peripheral nerve activity to the expression of the Phase 2 pressor, tachycardia, and flinch responses. After Phase 1 subsided, but before Phase 2 began, we locally anesthetized the ipsilateral or contralateral (control) hindpaw with a hydrophilic lidocaine derivative, QX- 314 (2%). Intraplantar QX-314 blocked Phase 2 pressor, tachycardia and behavioral responses only when injected into the paw that received formalin (2.5% or 10.0%). We conclude that persistent ongoing activity in peripheral afferent fibers during Phase 2 is required for the persistent pain evoked by formalin.

Original languageEnglish (US)
Pages (from-to)7575-7584
Number of pages10
JournalJournal of Neuroscience
Volume15
Issue number11
DOIs
StatePublished - Nov 1995

Keywords

  • QX-314
  • blood pressure
  • central sensitization
  • formalin
  • halothane
  • heart rate
  • nociception
  • pain
  • rat

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