Presynaptic inhibition and spinal pain processing in mice: a possible role of the NKCC1 cation-chloride co-transporter in hyperalgesia

Neurosci Lett. 2004 May 6;361(1-3):200-3. doi: 10.1016/j.neulet.2003.12.015.

Abstract

We have examined the role of the NKCC1 sodium-potassium-chloride-cotransporter in the generation of touch-evoked pain. The pain behavior of NKCC1 knockout mice (KO) was studied and compared to that of heterozygous (HE) and wild-type (WT) littermates. NKCC1 KO mice showed an increase in tail flick latencies and a reduction of the duration of pain behavior induced by intradermal capsaicin compared to HE and WT mice. All three groups of animals expressed a normal level of plasma extravasation following capsaicin applications. NKCC1 KO mice showed a reduction in stroking hyperalgesia (touch-evoked pain) compared to WT and HE mice but no differences were detected between the three groups in the expression of punctate hyperalgesia. As the NKCC1 co-transporter is responsible for the generation of presynaptic inhibition between afferent terminals in the spinal cord, these results support the notion that presynaptic interactions between low and high threshold afferents can underlie touch-evoked pain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Afferent Pathways / drug effects
  • Afferent Pathways / metabolism*
  • Afferent Pathways / physiopathology
  • Animals
  • Capsaicin / pharmacology
  • Hyperalgesia / chemically induced
  • Hyperalgesia / genetics
  • Hyperalgesia / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nerve Fibers, Unmyelinated / drug effects
  • Nerve Fibers, Unmyelinated / metabolism
  • Neural Inhibition / drug effects
  • Neural Inhibition / genetics*
  • Pain / chemically induced
  • Pain / genetics
  • Pain / metabolism*
  • Pain Measurement / drug effects
  • Pain Threshold / drug effects
  • Pain Threshold / physiology
  • Physical Stimulation
  • Posterior Horn Cells / drug effects
  • Posterior Horn Cells / metabolism
  • Posterior Horn Cells / physiopathology
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism*
  • Reaction Time / drug effects
  • Reaction Time / genetics
  • Sodium-Potassium-Chloride Symporters / genetics
  • Sodium-Potassium-Chloride Symporters / physiology*
  • Solute Carrier Family 12, Member 2
  • Spinal Nerve Roots / drug effects
  • Spinal Nerve Roots / metabolism
  • Spinal Nerve Roots / physiopathology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / genetics

Substances

  • Slc12a2 protein, mouse
  • Sodium-Potassium-Chloride Symporters
  • Solute Carrier Family 12, Member 2
  • Capsaicin