Sensitization of pain-modulating neurons in the rostral ventromedial medulla after peripheral nerve injury

Jonathan D. Carlson, Jennifer J. Maire, Melissa E. Martenson, Mary Heinricher

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

Nerve injury can lead to mechanical hypersensitivity in both humans and animal models, such that innocuous touch produces pain. Recent functional studies have demonstrated a critical role for descending pain-facilitating influences from the rostral ventromedial medulla (RVM) in neuropathic pain, but the underlying mechanisms and properties of the relevant neurons within the RVM are essentially unknown. We therefore characterized mechanical responsiveness of physiologically characterized neurons in the RVM after spinal nerve ligation, a model of neuropathic pain that produces robust mechanical hyperalgesia and allodynia. RVM neurons were studied 7-14 d after spinal nerve ligation, and classified as "on-cells," "off-cells," or "neutral cells" using standard criteria of changes in firing associated with heat-evoked reflexes. On-cells are known to promote nociception, and off-cells to suppress nociception, whereas the role of neutral cells in pain modulation remains an open question. Neuronal and behavioral responses to innocuous and noxious mechanical stimulation were tested using calibrated von Frey filaments (4 -100 g) applied to the hindpaws ipsilateral and contralateral to the injury, and in sham-operated and unoperated control animals. On- and off-cells recorded in nerve-injured animals exhibited novel responses to innocuous mechanical stimulation, and enhanced responses to noxious mechanical stimulation. Neuronal hypersensitivity in the RVM was correlated with behavioral hypersensitivity. Neutral cells remained unresponsive to cutaneous stimulation after nerve injury. These data demonstrate that both on- and off-cells in the RVM are sensitized to innocuous and noxious mechanical stimuli after nerve injury. This sensitization likely contributes to allodynia and hyperalgesia of neuropathic pain states.

Original languageEnglish (US)
Pages (from-to)13222-13231
Number of pages10
JournalJournal of Neuroscience
Volume27
Issue number48
DOIs
StatePublished - Nov 28 2007

Fingerprint

Peripheral Nerve Injuries
Neurons
Pain
Hyperalgesia
Neuralgia
Spinal Nerves
Hypersensitivity
Nociception
Wounds and Injuries
Ligation
Touch
Reflex
Animal Models
Hot Temperature
Skin

Keywords

  • Descending control
  • Neuropathic pain
  • Off-cells
  • On-cells
  • Pain modulation
  • Spinal nerve ligation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Sensitization of pain-modulating neurons in the rostral ventromedial medulla after peripheral nerve injury. / Carlson, Jonathan D.; Maire, Jennifer J.; Martenson, Melissa E.; Heinricher, Mary.

In: Journal of Neuroscience, Vol. 27, No. 48, 28.11.2007, p. 13222-13231.

Research output: Contribution to journalArticle

Carlson, Jonathan D. ; Maire, Jennifer J. ; Martenson, Melissa E. ; Heinricher, Mary. / Sensitization of pain-modulating neurons in the rostral ventromedial medulla after peripheral nerve injury. In: Journal of Neuroscience. 2007 ; Vol. 27, No. 48. pp. 13222-13231.
@article{384bb41d71e34e7f854052ad79641548,
title = "Sensitization of pain-modulating neurons in the rostral ventromedial medulla after peripheral nerve injury",
abstract = "Nerve injury can lead to mechanical hypersensitivity in both humans and animal models, such that innocuous touch produces pain. Recent functional studies have demonstrated a critical role for descending pain-facilitating influences from the rostral ventromedial medulla (RVM) in neuropathic pain, but the underlying mechanisms and properties of the relevant neurons within the RVM are essentially unknown. We therefore characterized mechanical responsiveness of physiologically characterized neurons in the RVM after spinal nerve ligation, a model of neuropathic pain that produces robust mechanical hyperalgesia and allodynia. RVM neurons were studied 7-14 d after spinal nerve ligation, and classified as {"}on-cells,{"} {"}off-cells,{"} or {"}neutral cells{"} using standard criteria of changes in firing associated with heat-evoked reflexes. On-cells are known to promote nociception, and off-cells to suppress nociception, whereas the role of neutral cells in pain modulation remains an open question. Neuronal and behavioral responses to innocuous and noxious mechanical stimulation were tested using calibrated von Frey filaments (4 -100 g) applied to the hindpaws ipsilateral and contralateral to the injury, and in sham-operated and unoperated control animals. On- and off-cells recorded in nerve-injured animals exhibited novel responses to innocuous mechanical stimulation, and enhanced responses to noxious mechanical stimulation. Neuronal hypersensitivity in the RVM was correlated with behavioral hypersensitivity. Neutral cells remained unresponsive to cutaneous stimulation after nerve injury. These data demonstrate that both on- and off-cells in the RVM are sensitized to innocuous and noxious mechanical stimuli after nerve injury. This sensitization likely contributes to allodynia and hyperalgesia of neuropathic pain states.",
keywords = "Descending control, Neuropathic pain, Off-cells, On-cells, Pain modulation, Spinal nerve ligation",
author = "Carlson, {Jonathan D.} and Maire, {Jennifer J.} and Martenson, {Melissa E.} and Mary Heinricher",
year = "2007",
month = "11",
day = "28",
doi = "10.1523/JNEUROSCI.3715-07.2007",
language = "English (US)",
volume = "27",
pages = "13222--13231",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "48",

}

TY - JOUR

T1 - Sensitization of pain-modulating neurons in the rostral ventromedial medulla after peripheral nerve injury

AU - Carlson, Jonathan D.

AU - Maire, Jennifer J.

AU - Martenson, Melissa E.

AU - Heinricher, Mary

PY - 2007/11/28

Y1 - 2007/11/28

N2 - Nerve injury can lead to mechanical hypersensitivity in both humans and animal models, such that innocuous touch produces pain. Recent functional studies have demonstrated a critical role for descending pain-facilitating influences from the rostral ventromedial medulla (RVM) in neuropathic pain, but the underlying mechanisms and properties of the relevant neurons within the RVM are essentially unknown. We therefore characterized mechanical responsiveness of physiologically characterized neurons in the RVM after spinal nerve ligation, a model of neuropathic pain that produces robust mechanical hyperalgesia and allodynia. RVM neurons were studied 7-14 d after spinal nerve ligation, and classified as "on-cells," "off-cells," or "neutral cells" using standard criteria of changes in firing associated with heat-evoked reflexes. On-cells are known to promote nociception, and off-cells to suppress nociception, whereas the role of neutral cells in pain modulation remains an open question. Neuronal and behavioral responses to innocuous and noxious mechanical stimulation were tested using calibrated von Frey filaments (4 -100 g) applied to the hindpaws ipsilateral and contralateral to the injury, and in sham-operated and unoperated control animals. On- and off-cells recorded in nerve-injured animals exhibited novel responses to innocuous mechanical stimulation, and enhanced responses to noxious mechanical stimulation. Neuronal hypersensitivity in the RVM was correlated with behavioral hypersensitivity. Neutral cells remained unresponsive to cutaneous stimulation after nerve injury. These data demonstrate that both on- and off-cells in the RVM are sensitized to innocuous and noxious mechanical stimuli after nerve injury. This sensitization likely contributes to allodynia and hyperalgesia of neuropathic pain states.

AB - Nerve injury can lead to mechanical hypersensitivity in both humans and animal models, such that innocuous touch produces pain. Recent functional studies have demonstrated a critical role for descending pain-facilitating influences from the rostral ventromedial medulla (RVM) in neuropathic pain, but the underlying mechanisms and properties of the relevant neurons within the RVM are essentially unknown. We therefore characterized mechanical responsiveness of physiologically characterized neurons in the RVM after spinal nerve ligation, a model of neuropathic pain that produces robust mechanical hyperalgesia and allodynia. RVM neurons were studied 7-14 d after spinal nerve ligation, and classified as "on-cells," "off-cells," or "neutral cells" using standard criteria of changes in firing associated with heat-evoked reflexes. On-cells are known to promote nociception, and off-cells to suppress nociception, whereas the role of neutral cells in pain modulation remains an open question. Neuronal and behavioral responses to innocuous and noxious mechanical stimulation were tested using calibrated von Frey filaments (4 -100 g) applied to the hindpaws ipsilateral and contralateral to the injury, and in sham-operated and unoperated control animals. On- and off-cells recorded in nerve-injured animals exhibited novel responses to innocuous mechanical stimulation, and enhanced responses to noxious mechanical stimulation. Neuronal hypersensitivity in the RVM was correlated with behavioral hypersensitivity. Neutral cells remained unresponsive to cutaneous stimulation after nerve injury. These data demonstrate that both on- and off-cells in the RVM are sensitized to innocuous and noxious mechanical stimuli after nerve injury. This sensitization likely contributes to allodynia and hyperalgesia of neuropathic pain states.

KW - Descending control

KW - Neuropathic pain

KW - Off-cells

KW - On-cells

KW - Pain modulation

KW - Spinal nerve ligation

UR - http://www.scopus.com/inward/record.url?scp=36849060297&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36849060297&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.3715-07.2007

DO - 10.1523/JNEUROSCI.3715-07.2007

M3 - Article

C2 - 18045916

AN - SCOPUS:36849060297

VL - 27

SP - 13222

EP - 13231

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 48

ER -