Descending facilitation maintains long-term spontaneous neuropathic pain

Ruizhong Wang, Tamara King, Milena De Felice, Wenhong Guo, Michael H. Ossipov, Frank Porreca

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)845-853
Number of pages9
JournalJournal of Pain
Volume14
Issue number8
DOIs
StatePublished - Aug 2013

Fingerprint

Spinal Nerves
Touch
Neuralgia
Ligation
Hypersensitivity
Pain
Hot Temperature
Lidocaine
Cholecystokinin B Receptor
Ondansetron
Serotonin Antagonists
Hyperalgesia
Microinjections
Pharmaceutical Preparations

Keywords

  • central sensitization
  • Nerve injury
  • neuropathic pain
  • rostral ventromedial medulla
  • spinal cord
  • spontaneous pain

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Neurology
  • Clinical Neurology

Cite this

Descending facilitation maintains long-term spontaneous neuropathic pain. / Wang, Ruizhong; King, Tamara; De Felice, Milena; Guo, Wenhong; Ossipov, Michael H.; Porreca, Frank.

In: Journal of Pain, Vol. 14, No. 8, 08.2013, p. 845-853.

Research output: Contribution to journalArticle

Wang, Ruizhong ; King, Tamara ; De Felice, Milena ; Guo, Wenhong ; Ossipov, Michael H. ; Porreca, Frank. / Descending facilitation maintains long-term spontaneous neuropathic pain. In: Journal of Pain. 2013 ; Vol. 14, No. 8. pp. 845-853.
@article{f4dc01ae6cb5453c99960abf800459eb,
title = "Descending facilitation maintains long-term spontaneous neuropathic pain",
abstract = "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 = "central sensitization, Nerve injury, neuropathic pain, rostral ventromedial medulla, spinal cord, spontaneous pain",
author = "Ruizhong Wang and Tamara King and {De Felice}, Milena and Wenhong Guo and Ossipov, {Michael H.} and Frank Porreca",
year = "2013",
month = "8",
doi = "10.1016/j.jpain.2013.02.011",
language = "English (US)",
volume = "14",
pages = "845--853",
journal = "Journal of Pain",
issn = "1526-5900",
publisher = "Churchill Livingstone",
number = "8",

}

TY - JOUR

T1 - Descending facilitation maintains long-term spontaneous neuropathic pain

AU - Wang, Ruizhong

AU - King, Tamara

AU - De Felice, Milena

AU - Guo, Wenhong

AU - Ossipov, Michael H.

AU - Porreca, Frank

PY - 2013/8

Y1 - 2013/8

N2 - 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.

AB - 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.

KW - central sensitization

KW - Nerve injury

KW - neuropathic pain

KW - rostral ventromedial medulla

KW - spinal cord

KW - spontaneous pain

UR - http://www.scopus.com/inward/record.url?scp=84881153259&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84881153259&partnerID=8YFLogxK

U2 - 10.1016/j.jpain.2013.02.011

DO - 10.1016/j.jpain.2013.02.011

M3 - Article

C2 - 23602267

AN - SCOPUS:84881153259

VL - 14

SP - 845

EP - 853

JO - Journal of Pain

JF - Journal of Pain

SN - 1526-5900

IS - 8

ER -