Cytokine involvement in dynorphin-induced allodynia

Tinna M. Laughlin, John R. Bethea, Robert P. Yezierski, George L. Wilcox

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

Dynorphin A is an endogenous opioid peptide, which has previously been shown to produce a long-lasting allodynia and hyperalgesia in mice, behavioral states consistent with signs of clinically observed neuropathic pain. This dynorphin-induced allodynia was used as a pharmacological, central model of neuropathic pain. In this study, we examined the involvement of the cytokine IL-1β, the transcription factor nuclear factor kappa B (NF-κB), and de novo protein synthesis in the development of allodynia induced by intrathecal (i.t.) administration of dynorphin in male ICR mice. Pretreatment with the protein synthesis inhibitor cycloheximide (0.3-85nmol), the NF-κB inhibitor pyrrolidinedithiocarbamate (PDTC) (0.001-1000pmol), the IL-1 receptor antagonist (IL-1ra) protein (0.01-100ng), the caspase-1 inhibitor (YVAD) (0.1-300pmol), and the anti-inflammatory cytokine IL-10 (0.1-300ng) all dose-dependently reduced the induction of dynorphin-induced allodynia. Finally, IL-10 administered within the first 24h after the dynorphin insult prevented the development of chronic allodynia. These results demonstrate that the anti-inflammatory cytokines IL-10 and IL-1ra impede the development of dynorphin-induced allodynia. These results also suggest that production of new proteins through NF-κB activation is required for the induction of allodynia. We speculate that IL-1ra, IL-10, PDTC and cycloheximide interfere with the central pro-inflammatory cascade. Modulation of cytokine activity in the spinal cord may therefore prove to be an effective therapeutic strategy for the treatment of chronic pain. Copyright (C) 2000 International Association for the Study of Pain. Published by Elsevier Science B.V.

Original languageEnglish
Pages (from-to)159-167
Number of pages9
JournalPain
Volume84
Issue number2-3
DOIs
StatePublished - Feb 1 2000

Fingerprint

Dynorphins
Hyperalgesia
Cytokines
Interleukin-10
Interleukin-1 Receptors
NF-kappa B
Neuralgia
Cycloheximide
Anti-Inflammatory Agents
Inbred ICR Mouse
Proteins
Protein Synthesis Inhibitors
Opioid Peptides
Interleukin-1
Chronic Pain
Spinal Cord
Transcription Factors
Pharmacology
Therapeutics

Keywords

  • Cytokines
  • IL-10
  • Interleukin-1beta
  • Neuropathic pain
  • NF-κB
  • Protein synthesis

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Neurology
  • Neuroscience(all)
  • Pharmacology
  • Clinical Psychology

Cite this

Laughlin, T. M., Bethea, J. R., Yezierski, R. P., & Wilcox, G. L. (2000). Cytokine involvement in dynorphin-induced allodynia. Pain, 84(2-3), 159-167. https://doi.org/10.1016/S0304-3959(99)00195-5

Cytokine involvement in dynorphin-induced allodynia. / Laughlin, Tinna M.; Bethea, John R.; Yezierski, Robert P.; Wilcox, George L.

In: Pain, Vol. 84, No. 2-3, 01.02.2000, p. 159-167.

Research output: Contribution to journalArticle

Laughlin, TM, Bethea, JR, Yezierski, RP & Wilcox, GL 2000, 'Cytokine involvement in dynorphin-induced allodynia', Pain, vol. 84, no. 2-3, pp. 159-167. https://doi.org/10.1016/S0304-3959(99)00195-5
Laughlin TM, Bethea JR, Yezierski RP, Wilcox GL. Cytokine involvement in dynorphin-induced allodynia. Pain. 2000 Feb 1;84(2-3):159-167. https://doi.org/10.1016/S0304-3959(99)00195-5
Laughlin, Tinna M. ; Bethea, John R. ; Yezierski, Robert P. ; Wilcox, George L. / Cytokine involvement in dynorphin-induced allodynia. In: Pain. 2000 ; Vol. 84, No. 2-3. pp. 159-167.
@article{5d8e56cc289c4f06a1b11952d1305567,
title = "Cytokine involvement in dynorphin-induced allodynia",
abstract = "Dynorphin A is an endogenous opioid peptide, which has previously been shown to produce a long-lasting allodynia and hyperalgesia in mice, behavioral states consistent with signs of clinically observed neuropathic pain. This dynorphin-induced allodynia was used as a pharmacological, central model of neuropathic pain. In this study, we examined the involvement of the cytokine IL-1β, the transcription factor nuclear factor kappa B (NF-κB), and de novo protein synthesis in the development of allodynia induced by intrathecal (i.t.) administration of dynorphin in male ICR mice. Pretreatment with the protein synthesis inhibitor cycloheximide (0.3-85nmol), the NF-κB inhibitor pyrrolidinedithiocarbamate (PDTC) (0.001-1000pmol), the IL-1 receptor antagonist (IL-1ra) protein (0.01-100ng), the caspase-1 inhibitor (YVAD) (0.1-300pmol), and the anti-inflammatory cytokine IL-10 (0.1-300ng) all dose-dependently reduced the induction of dynorphin-induced allodynia. Finally, IL-10 administered within the first 24h after the dynorphin insult prevented the development of chronic allodynia. These results demonstrate that the anti-inflammatory cytokines IL-10 and IL-1ra impede the development of dynorphin-induced allodynia. These results also suggest that production of new proteins through NF-κB activation is required for the induction of allodynia. We speculate that IL-1ra, IL-10, PDTC and cycloheximide interfere with the central pro-inflammatory cascade. Modulation of cytokine activity in the spinal cord may therefore prove to be an effective therapeutic strategy for the treatment of chronic pain. Copyright (C) 2000 International Association for the Study of Pain. Published by Elsevier Science B.V.",
keywords = "Cytokines, IL-10, Interleukin-1beta, Neuropathic pain, NF-κB, Protein synthesis",
author = "Laughlin, {Tinna M.} and Bethea, {John R.} and Yezierski, {Robert P.} and Wilcox, {George L.}",
year = "2000",
month = "2",
day = "1",
doi = "10.1016/S0304-3959(99)00195-5",
language = "English",
volume = "84",
pages = "159--167",
journal = "Pain",
issn = "0304-3959",
publisher = "Elsevier",
number = "2-3",

}

TY - JOUR

T1 - Cytokine involvement in dynorphin-induced allodynia

AU - Laughlin, Tinna M.

AU - Bethea, John R.

AU - Yezierski, Robert P.

AU - Wilcox, George L.

PY - 2000/2/1

Y1 - 2000/2/1

N2 - Dynorphin A is an endogenous opioid peptide, which has previously been shown to produce a long-lasting allodynia and hyperalgesia in mice, behavioral states consistent with signs of clinically observed neuropathic pain. This dynorphin-induced allodynia was used as a pharmacological, central model of neuropathic pain. In this study, we examined the involvement of the cytokine IL-1β, the transcription factor nuclear factor kappa B (NF-κB), and de novo protein synthesis in the development of allodynia induced by intrathecal (i.t.) administration of dynorphin in male ICR mice. Pretreatment with the protein synthesis inhibitor cycloheximide (0.3-85nmol), the NF-κB inhibitor pyrrolidinedithiocarbamate (PDTC) (0.001-1000pmol), the IL-1 receptor antagonist (IL-1ra) protein (0.01-100ng), the caspase-1 inhibitor (YVAD) (0.1-300pmol), and the anti-inflammatory cytokine IL-10 (0.1-300ng) all dose-dependently reduced the induction of dynorphin-induced allodynia. Finally, IL-10 administered within the first 24h after the dynorphin insult prevented the development of chronic allodynia. These results demonstrate that the anti-inflammatory cytokines IL-10 and IL-1ra impede the development of dynorphin-induced allodynia. These results also suggest that production of new proteins through NF-κB activation is required for the induction of allodynia. We speculate that IL-1ra, IL-10, PDTC and cycloheximide interfere with the central pro-inflammatory cascade. Modulation of cytokine activity in the spinal cord may therefore prove to be an effective therapeutic strategy for the treatment of chronic pain. Copyright (C) 2000 International Association for the Study of Pain. Published by Elsevier Science B.V.

AB - Dynorphin A is an endogenous opioid peptide, which has previously been shown to produce a long-lasting allodynia and hyperalgesia in mice, behavioral states consistent with signs of clinically observed neuropathic pain. This dynorphin-induced allodynia was used as a pharmacological, central model of neuropathic pain. In this study, we examined the involvement of the cytokine IL-1β, the transcription factor nuclear factor kappa B (NF-κB), and de novo protein synthesis in the development of allodynia induced by intrathecal (i.t.) administration of dynorphin in male ICR mice. Pretreatment with the protein synthesis inhibitor cycloheximide (0.3-85nmol), the NF-κB inhibitor pyrrolidinedithiocarbamate (PDTC) (0.001-1000pmol), the IL-1 receptor antagonist (IL-1ra) protein (0.01-100ng), the caspase-1 inhibitor (YVAD) (0.1-300pmol), and the anti-inflammatory cytokine IL-10 (0.1-300ng) all dose-dependently reduced the induction of dynorphin-induced allodynia. Finally, IL-10 administered within the first 24h after the dynorphin insult prevented the development of chronic allodynia. These results demonstrate that the anti-inflammatory cytokines IL-10 and IL-1ra impede the development of dynorphin-induced allodynia. These results also suggest that production of new proteins through NF-κB activation is required for the induction of allodynia. We speculate that IL-1ra, IL-10, PDTC and cycloheximide interfere with the central pro-inflammatory cascade. Modulation of cytokine activity in the spinal cord may therefore prove to be an effective therapeutic strategy for the treatment of chronic pain. Copyright (C) 2000 International Association for the Study of Pain. Published by Elsevier Science B.V.

KW - Cytokines

KW - IL-10

KW - Interleukin-1beta

KW - Neuropathic pain

KW - NF-κB

KW - Protein synthesis

UR - http://www.scopus.com/inward/record.url?scp=0033968757&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033968757&partnerID=8YFLogxK

U2 - 10.1016/S0304-3959(99)00195-5

DO - 10.1016/S0304-3959(99)00195-5

M3 - Article

VL - 84

SP - 159

EP - 167

JO - Pain

JF - Pain

SN - 0304-3959

IS - 2-3

ER -