Effect of adenosine A1 receptor agonist on the enhanced excitability of spinal dorsal horn neurons after peripheral nerve injury

Daisuke Yamaguchi, Ryuji Terayama, Shinji Omura, Hiroki Tsuchiya, Tadasu Sato, Hiroyuki Ichikawa, Tomosada Sugimoto

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Neuronal hyperactivity has been implicated in abnormal pain sensation following peripheral nerve injuries. Previous studies have indicated that the activation of adenosine A1 receptors (A1R) in the central and peripheral nervous systems produces an antinociceptive effect. However, the mechanisms involved in the peripheral effect are still not fully understood. The effects of the local application of the selective A1R agonist, 2-chloro-N(6)-cyclopentyladenosine (CCPA) on neuronal hyperactivity were examined in this study using a neuropathic pain model induced by a tibial nerve injury. We utilized Fos protein-like immunoreactivity induced by noxious heat stimulation to examine changes in the number of Fos protein like immunoreactive (Fos-LI) neuron profiles in the spinal dorsal horn, and behavioral analysis for mechanical and thermal sensitivities. The nerve injury induced an exaggerated Fos response to noxious heat stimulation. The number of Fos-LI neuron profiles was significantly decreased and their distribution was restricted to the central terminal field of the spared peroneal nerve 3 days after the injury. The number of Fos-LI neuron profiles returned to control levels and a large number of these profiles were observed in the central terminal field of the injured tibial nerve 14 days after the injury. These enhanced Fos responses were attenuated by the local application of CCPA. The nerve injury also resulted in mechanical allodynia and thermal hyperalgesia. The local application of CCPA inhibited thermal hyperalgesia, but was less effective against mechanical allodynia. These results indicated that activation of peripheral A1R plays a role in the regulation of nerve injury-induced hyperalgesia.

Original languageEnglish
Pages (from-to)213-222
Number of pages10
JournalInternational Journal of Neuroscience
Volume124
Issue number3
DOIs
Publication statusPublished - Mar 2014

Fingerprint

Adenosine A1 Receptor Agonists
Posterior Horn Cells
Peripheral Nerve Injuries
Hyperalgesia
Wounds and Injuries
Tibial Nerve
2-chloro-N(6)cyclopentyladenosine
Hot Temperature
Neurons
Proteins
Adenosine A1 Receptors
Peroneal Nerve
Peripheral Nervous System
Neuralgia
Central Nervous System
Pain

Keywords

  • Adenosine
  • Behavior
  • C-Fos
  • Neuropathic pain
  • Spinal cord

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Effect of adenosine A1 receptor agonist on the enhanced excitability of spinal dorsal horn neurons after peripheral nerve injury. / Yamaguchi, Daisuke; Terayama, Ryuji; Omura, Shinji; Tsuchiya, Hiroki; Sato, Tadasu; Ichikawa, Hiroyuki; Sugimoto, Tomosada.

In: International Journal of Neuroscience, Vol. 124, No. 3, 03.2014, p. 213-222.

Research output: Contribution to journalArticle

Yamaguchi, Daisuke ; Terayama, Ryuji ; Omura, Shinji ; Tsuchiya, Hiroki ; Sato, Tadasu ; Ichikawa, Hiroyuki ; Sugimoto, Tomosada. / Effect of adenosine A1 receptor agonist on the enhanced excitability of spinal dorsal horn neurons after peripheral nerve injury. In: International Journal of Neuroscience. 2014 ; Vol. 124, No. 3. pp. 213-222.
@article{c5d758e6fcd144329ca3d66fead9e0d2,
title = "Effect of adenosine A1 receptor agonist on the enhanced excitability of spinal dorsal horn neurons after peripheral nerve injury",
abstract = "Neuronal hyperactivity has been implicated in abnormal pain sensation following peripheral nerve injuries. Previous studies have indicated that the activation of adenosine A1 receptors (A1R) in the central and peripheral nervous systems produces an antinociceptive effect. However, the mechanisms involved in the peripheral effect are still not fully understood. The effects of the local application of the selective A1R agonist, 2-chloro-N(6)-cyclopentyladenosine (CCPA) on neuronal hyperactivity were examined in this study using a neuropathic pain model induced by a tibial nerve injury. We utilized Fos protein-like immunoreactivity induced by noxious heat stimulation to examine changes in the number of Fos protein like immunoreactive (Fos-LI) neuron profiles in the spinal dorsal horn, and behavioral analysis for mechanical and thermal sensitivities. The nerve injury induced an exaggerated Fos response to noxious heat stimulation. The number of Fos-LI neuron profiles was significantly decreased and their distribution was restricted to the central terminal field of the spared peroneal nerve 3 days after the injury. The number of Fos-LI neuron profiles returned to control levels and a large number of these profiles were observed in the central terminal field of the injured tibial nerve 14 days after the injury. These enhanced Fos responses were attenuated by the local application of CCPA. The nerve injury also resulted in mechanical allodynia and thermal hyperalgesia. The local application of CCPA inhibited thermal hyperalgesia, but was less effective against mechanical allodynia. These results indicated that activation of peripheral A1R plays a role in the regulation of nerve injury-induced hyperalgesia.",
keywords = "Adenosine, Behavior, C-Fos, Neuropathic pain, Spinal cord",
author = "Daisuke Yamaguchi and Ryuji Terayama and Shinji Omura and Hiroki Tsuchiya and Tadasu Sato and Hiroyuki Ichikawa and Tomosada Sugimoto",
year = "2014",
month = "3",
doi = "10.3109/00207454.2013.842566",
language = "English",
volume = "124",
pages = "213--222",
journal = "International Journal of Neuroscience",
issn = "0020-7454",
publisher = "Informa Healthcare",
number = "3",

}

TY - JOUR

T1 - Effect of adenosine A1 receptor agonist on the enhanced excitability of spinal dorsal horn neurons after peripheral nerve injury

AU - Yamaguchi, Daisuke

AU - Terayama, Ryuji

AU - Omura, Shinji

AU - Tsuchiya, Hiroki

AU - Sato, Tadasu

AU - Ichikawa, Hiroyuki

AU - Sugimoto, Tomosada

PY - 2014/3

Y1 - 2014/3

N2 - Neuronal hyperactivity has been implicated in abnormal pain sensation following peripheral nerve injuries. Previous studies have indicated that the activation of adenosine A1 receptors (A1R) in the central and peripheral nervous systems produces an antinociceptive effect. However, the mechanisms involved in the peripheral effect are still not fully understood. The effects of the local application of the selective A1R agonist, 2-chloro-N(6)-cyclopentyladenosine (CCPA) on neuronal hyperactivity were examined in this study using a neuropathic pain model induced by a tibial nerve injury. We utilized Fos protein-like immunoreactivity induced by noxious heat stimulation to examine changes in the number of Fos protein like immunoreactive (Fos-LI) neuron profiles in the spinal dorsal horn, and behavioral analysis for mechanical and thermal sensitivities. The nerve injury induced an exaggerated Fos response to noxious heat stimulation. The number of Fos-LI neuron profiles was significantly decreased and their distribution was restricted to the central terminal field of the spared peroneal nerve 3 days after the injury. The number of Fos-LI neuron profiles returned to control levels and a large number of these profiles were observed in the central terminal field of the injured tibial nerve 14 days after the injury. These enhanced Fos responses were attenuated by the local application of CCPA. The nerve injury also resulted in mechanical allodynia and thermal hyperalgesia. The local application of CCPA inhibited thermal hyperalgesia, but was less effective against mechanical allodynia. These results indicated that activation of peripheral A1R plays a role in the regulation of nerve injury-induced hyperalgesia.

AB - Neuronal hyperactivity has been implicated in abnormal pain sensation following peripheral nerve injuries. Previous studies have indicated that the activation of adenosine A1 receptors (A1R) in the central and peripheral nervous systems produces an antinociceptive effect. However, the mechanisms involved in the peripheral effect are still not fully understood. The effects of the local application of the selective A1R agonist, 2-chloro-N(6)-cyclopentyladenosine (CCPA) on neuronal hyperactivity were examined in this study using a neuropathic pain model induced by a tibial nerve injury. We utilized Fos protein-like immunoreactivity induced by noxious heat stimulation to examine changes in the number of Fos protein like immunoreactive (Fos-LI) neuron profiles in the spinal dorsal horn, and behavioral analysis for mechanical and thermal sensitivities. The nerve injury induced an exaggerated Fos response to noxious heat stimulation. The number of Fos-LI neuron profiles was significantly decreased and their distribution was restricted to the central terminal field of the spared peroneal nerve 3 days after the injury. The number of Fos-LI neuron profiles returned to control levels and a large number of these profiles were observed in the central terminal field of the injured tibial nerve 14 days after the injury. These enhanced Fos responses were attenuated by the local application of CCPA. The nerve injury also resulted in mechanical allodynia and thermal hyperalgesia. The local application of CCPA inhibited thermal hyperalgesia, but was less effective against mechanical allodynia. These results indicated that activation of peripheral A1R plays a role in the regulation of nerve injury-induced hyperalgesia.

KW - Adenosine

KW - Behavior

KW - C-Fos

KW - Neuropathic pain

KW - Spinal cord

UR - http://www.scopus.com/inward/record.url?scp=84893658755&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84893658755&partnerID=8YFLogxK

U2 - 10.3109/00207454.2013.842566

DO - 10.3109/00207454.2013.842566

M3 - Article

C2 - 24016034

AN - SCOPUS:84893658755

VL - 124

SP - 213

EP - 222

JO - International Journal of Neuroscience

JF - International Journal of Neuroscience

SN - 0020-7454

IS - 3

ER -