A3 adenosine receptor agonist attenuates neuropathic pain by suppressing activation of microglia and convergence of nociceptive inputs in the spinal dorsal horn

Ryuji Terayama, Mitsuyasu Tabata, Kotaro Maruhama, Seiji Iida

Research output: Contribution to journalArticle

Abstract

Peripheral nerve injuries cause glial activation and neuronal hyperactivity in the spinal dorsal horn. These changes have been considered to be involved in the underlying mechanisms for the development and maintenance of neuropathic pain. Using double immunofluorescence labeling, we previously demonstrated that spinal microglial activation induced by nerve injury enhanced convergence of nociceptive inputs in the spinal dorsal horn from uninjured afferents. The adenosine A3 receptor (A3AR) agonists have been shown to have antinociceptive activities in several experimental neuropathic pain models. However, the mechanisms underlying these antinociceptive actions of the A3AR agonist are still not fully explored. In this study, the effects of the A3AR agonist (i.e., IB-MECA) on microglial activation, enhancement of convergent nociceptive inputs, and nocifensive behaviors were examined after tibial nerve injury. Injury to the tibial nerve initially caused hyposensitivity to touch stimulus at 3 days, and then resulted in tactile allodynia at 14-day post-injury. The daily systemic administration of IB-MECA (0.1 mg/kg/day) for 8 days in a row starting on the day of nerve injury or 7 days after nerve injury prevented the development of behaviorally assessed hypersensitivities, and spinal microglial activation induced by nerve injury. These treatments also suppressed anomalous convergence of nociceptive primary inputs in the spinal dorsal horn. The present findings indicate that the A3AR agonist attenuates neuropathic pain states by suppressing enhanced microglial activation, and anomalous convergence of nociceptive inputs in the spinal dorsal horn from uninjured afferents after injury to the peripheral nerve.

LanguageEnglish
JournalExperimental Brain Research
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Adenosine A3 Receptor Agonists
Microglia
Neuralgia
Wounds and Injuries
Peripheral Nerve Injuries
Tibial Nerve
Hyperalgesia
Touch
Spinal Cord Dorsal Horn
Neuroglia
Fluorescent Antibody Technique
Hypersensitivity
Maintenance

Keywords

  • AAR
  • Adenosine
  • Microglia
  • Nerve injury
  • Spinal dorsal horn

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

@article{ca40913591f24218923685a35f8cc0dc,
title = "A3 adenosine receptor agonist attenuates neuropathic pain by suppressing activation of microglia and convergence of nociceptive inputs in the spinal dorsal horn",
abstract = "Peripheral nerve injuries cause glial activation and neuronal hyperactivity in the spinal dorsal horn. These changes have been considered to be involved in the underlying mechanisms for the development and maintenance of neuropathic pain. Using double immunofluorescence labeling, we previously demonstrated that spinal microglial activation induced by nerve injury enhanced convergence of nociceptive inputs in the spinal dorsal horn from uninjured afferents. The adenosine A3 receptor (A3AR) agonists have been shown to have antinociceptive activities in several experimental neuropathic pain models. However, the mechanisms underlying these antinociceptive actions of the A3AR agonist are still not fully explored. In this study, the effects of the A3AR agonist (i.e., IB-MECA) on microglial activation, enhancement of convergent nociceptive inputs, and nocifensive behaviors were examined after tibial nerve injury. Injury to the tibial nerve initially caused hyposensitivity to touch stimulus at 3 days, and then resulted in tactile allodynia at 14-day post-injury. The daily systemic administration of IB-MECA (0.1 mg/kg/day) for 8 days in a row starting on the day of nerve injury or 7 days after nerve injury prevented the development of behaviorally assessed hypersensitivities, and spinal microglial activation induced by nerve injury. These treatments also suppressed anomalous convergence of nociceptive primary inputs in the spinal dorsal horn. The present findings indicate that the A3AR agonist attenuates neuropathic pain states by suppressing enhanced microglial activation, and anomalous convergence of nociceptive inputs in the spinal dorsal horn from uninjured afferents after injury to the peripheral nerve.",
keywords = "AAR, Adenosine, Microglia, Nerve injury, Spinal dorsal horn",
author = "Ryuji Terayama and Mitsuyasu Tabata and Kotaro Maruhama and Seiji Iida",
year = "2018",
month = "1",
day = "1",
doi = "10.1007/s00221-018-5377-1",
language = "English",
journal = "Experimental Brain Research",
issn = "0014-4819",
publisher = "Springer Verlag",

}

TY - JOUR

T1 - A3 adenosine receptor agonist attenuates neuropathic pain by suppressing activation of microglia and convergence of nociceptive inputs in the spinal dorsal horn

AU - Terayama, Ryuji

AU - Tabata, Mitsuyasu

AU - Maruhama, Kotaro

AU - Iida, Seiji

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Peripheral nerve injuries cause glial activation and neuronal hyperactivity in the spinal dorsal horn. These changes have been considered to be involved in the underlying mechanisms for the development and maintenance of neuropathic pain. Using double immunofluorescence labeling, we previously demonstrated that spinal microglial activation induced by nerve injury enhanced convergence of nociceptive inputs in the spinal dorsal horn from uninjured afferents. The adenosine A3 receptor (A3AR) agonists have been shown to have antinociceptive activities in several experimental neuropathic pain models. However, the mechanisms underlying these antinociceptive actions of the A3AR agonist are still not fully explored. In this study, the effects of the A3AR agonist (i.e., IB-MECA) on microglial activation, enhancement of convergent nociceptive inputs, and nocifensive behaviors were examined after tibial nerve injury. Injury to the tibial nerve initially caused hyposensitivity to touch stimulus at 3 days, and then resulted in tactile allodynia at 14-day post-injury. The daily systemic administration of IB-MECA (0.1 mg/kg/day) for 8 days in a row starting on the day of nerve injury or 7 days after nerve injury prevented the development of behaviorally assessed hypersensitivities, and spinal microglial activation induced by nerve injury. These treatments also suppressed anomalous convergence of nociceptive primary inputs in the spinal dorsal horn. The present findings indicate that the A3AR agonist attenuates neuropathic pain states by suppressing enhanced microglial activation, and anomalous convergence of nociceptive inputs in the spinal dorsal horn from uninjured afferents after injury to the peripheral nerve.

AB - Peripheral nerve injuries cause glial activation and neuronal hyperactivity in the spinal dorsal horn. These changes have been considered to be involved in the underlying mechanisms for the development and maintenance of neuropathic pain. Using double immunofluorescence labeling, we previously demonstrated that spinal microglial activation induced by nerve injury enhanced convergence of nociceptive inputs in the spinal dorsal horn from uninjured afferents. The adenosine A3 receptor (A3AR) agonists have been shown to have antinociceptive activities in several experimental neuropathic pain models. However, the mechanisms underlying these antinociceptive actions of the A3AR agonist are still not fully explored. In this study, the effects of the A3AR agonist (i.e., IB-MECA) on microglial activation, enhancement of convergent nociceptive inputs, and nocifensive behaviors were examined after tibial nerve injury. Injury to the tibial nerve initially caused hyposensitivity to touch stimulus at 3 days, and then resulted in tactile allodynia at 14-day post-injury. The daily systemic administration of IB-MECA (0.1 mg/kg/day) for 8 days in a row starting on the day of nerve injury or 7 days after nerve injury prevented the development of behaviorally assessed hypersensitivities, and spinal microglial activation induced by nerve injury. These treatments also suppressed anomalous convergence of nociceptive primary inputs in the spinal dorsal horn. The present findings indicate that the A3AR agonist attenuates neuropathic pain states by suppressing enhanced microglial activation, and anomalous convergence of nociceptive inputs in the spinal dorsal horn from uninjured afferents after injury to the peripheral nerve.

KW - AAR

KW - Adenosine

KW - Microglia

KW - Nerve injury

KW - Spinal dorsal horn

UR - http://www.scopus.com/inward/record.url?scp=85053378174&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053378174&partnerID=8YFLogxK

U2 - 10.1007/s00221-018-5377-1

DO - 10.1007/s00221-018-5377-1

M3 - Article

JO - Experimental Brain Research

T2 - Experimental Brain Research

JF - Experimental Brain Research

SN - 0014-4819

ER -