Descending facilitation maintains long-term spontaneous neuropathic pain

J Pain. 2013 Aug;14(8):845-53. doi: 10.1016/j.jpain.2013.02.011. Epub 2013 Apr 19.


Neuropathic pain is frequently characterized by spontaneous pain (ie, pain at rest) and, in some cases, by cold- and touch-induced allodynia. Mechanisms underlying the chronicity of neuropathic pain are not well understood. Rats received spinal nerve ligation (SNL) and were monitored for tactile and thermal thresholds. While heat hypersensitivity returned to baseline levels within approximately 35 to 40 days, tactile hypersensitivity was still present at 580 days after SNL. Tactile hypersensitivity at post-SNL day 60 (D60) was reversed by microinjection of 1) lidocaine; 2) a cholecystokinin 2 receptor antagonist into the rostral ventromedial medulla; or 3) dorsolateral funiculus lesion. Rostral ventromedial medulla lidocaine at D60 or spinal ondansetron, a 5-hydroxytryptamine 3 antagonist, at post-SNL D42 produced conditioned place preference selectively in SNL-treated rats, suggesting long-lasting spontaneous pain. Touch-induced FOS was increased in the spinal dorsal horn of SNL rats at D60 and prevented by prior dorsolateral funiculus lesion, suggesting that long-lasting tactile hypersensitivity depends upon spinal sensitization, which is mediated in part by descending facilitation, in spite of resolution of heat hypersensitivity.

Perspective: These data suggest that spontaneous pain is present for an extended period of time and, consistent with likely actions of clinically effective drugs, is maintained by descending facilitation.

Keywords: Nerve injury; central sensitization; neuropathic pain; rostral ventromedial medulla; spinal cord; spontaneous pain.

Publication types

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

MeSH terms

  • Afferent Pathways / drug effects
  • Afferent Pathways / physiology*
  • Anesthetics, Local / pharmacology
  • Anesthetics, Local / radiation effects
  • Anesthetics, Local / therapeutic use
  • Animals
  • Benzodiazepines / pharmacology
  • Benzodiazepines / therapeutic use
  • Conditioning, Operant / drug effects
  • Disease Models, Animal
  • Hormone Antagonists / pharmacology
  • Hormone Antagonists / therapeutic use
  • Hyperalgesia / physiopathology
  • Lidocaine / pharmacology
  • Lidocaine / therapeutic use
  • Male
  • Medulla Oblongata / drug effects
  • Medulla Oblongata / physiology
  • Neuralgia / drug therapy
  • Neuralgia / physiopathology*
  • Oncogene Proteins v-fos / metabolism
  • Ondansetron / pharmacology
  • Ondansetron / therapeutic use
  • Pain Measurement
  • Pain Threshold / drug effects
  • Pain Threshold / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin Antagonists / therapeutic use
  • Spinal Nerves / injuries
  • Time Factors


  • Anesthetics, Local
  • Hormone Antagonists
  • Oncogene Proteins v-fos
  • Serotonin Antagonists
  • Benzodiazepines
  • YM 022
  • Ondansetron
  • Lidocaine