Nociceptive plasticity inhibits adaptive learning in the spinal cord

Neuroscience. 2006 Aug 11;141(1):421-31. doi: 10.1016/j.neuroscience.2006.03.029. Epub 2006 May 6.

Abstract

Spinal plasticity is known to play a role in central neurogenic pain. Over the last 100 years researchers have found that the spinal cord is also capable of supporting other forms of plasticity including several forms of learning. To study instrumental (response-outcome) learning in the spinal cord, we use a preparation in which spinally transected rats are given shock to the hind leg when the leg is extended. The spinal cord rapidly learns to hold the leg in a flexed position when given this controllable shock. However, if shock is independent of leg position (uncontrollable shock), subjects fail to learn. Uncontrollable shock also impairs future learning. As little as 6 min of uncontrollable shock to either the leg or the tail generates a learning deficit that lasts up to 48 h. Recent data suggest links between the learning deficit and the sensitization of pain circuits associated with inflammation or injury (central sensitization). Here, we explored whether central sensitization and the spinal learning deficit share pharmacological and behavioral features. Central sensitization enhances reactivity to mechanical stimulation (allodynia) and depends on the N-methyl-d-aspartate receptor (NMDAR). The uncontrollable shock stimulus that generates a learning deficit produced a tactile allodynia (Exp. 1) and administration of the NMDAR antagonist MK-801 blocked induction of the learning deficit (Exp. 2). Finally, a treatment known to induce central sensitization, intradermal carrageenan, produced a spinal learning deficit (Exp. 3). The findings suggest that the induction of central sensitization inhibits selective response modifications.

Publication types

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

MeSH terms

  • Analysis of Variance
  • Animals
  • Behavior, Animal
  • Carrageenan / pharmacology
  • Conditioning, Psychological / drug effects
  • Conditioning, Psychological / physiology*
  • Dizocilpine Maleate / pharmacology
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Antagonists / pharmacology
  • Functional Laterality
  • Inhibition, Psychological*
  • Male
  • Models, Biological
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Nociceptors / drug effects
  • Nociceptors / physiopathology*
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord / cytology
  • Spinal Cord / drug effects
  • Spinal Cord / physiopathology*
  • Spinal Cord Injuries / drug therapy
  • Spinal Cord Injuries / physiopathology

Substances

  • Excitatory Amino Acid Antagonists
  • Dizocilpine Maleate
  • Carrageenan