Peripheral acid-sensing ion channels and P2X receptors contribute to mechanical allodynia in a rodent thrombus-induced ischemic pain model

Hyoung Sig Seo, Dae Hyun Roh, Seo Yeon Yoon, Suk Yun Kang, Ji Young Moon, Hyun Woo Kim, Ho Jae Han, Jin Chung, Alvin J. Beitz, Jang Hern Lee

Research output: Contribution to journalArticle

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Abstract

We have previously established a thrombus-induced ischemic pain (TIIP) model in the rat, which mimics the pathophysiology of ischemic pain in patients with peripheral arterial disease. Because ischemia commonly induces acidosis and ATP release, one of the goals of this study was to investigate the role of acid-sensing ion channels (ASICs), transient receptor potential vanilloid-1 (TRPV1) receptors, and P2X receptors in the maintenance of ischemia-induced mechanical allodynia (MA). To test this, amiloride (an ASIC blocker), AMG-9810 (a TRPV1 blocker), or PPADS (a P2Xs antagonist) was intraplantarly injected at day 3 after FeCl2 application onto the femoral artery. Ipsilateral administration of amiloride or PPADS but not AMG-9810 dose-dependently reduced MA. However, contralateral amiloride or PPADS did not suppress contralateral MA. Interestingly, co-administration of submaximal doses of amiloride and PPADS produced a significantly prolonged suppression of MA. Furthermore, ipsilateral EGTA (a calcium chelator) or chelerythrine (a protein kinase C inhibitor) also significantly reduced MA. Collectively, these findings suggest that peripheral ASICs and P2X receptors are involved in the maintenance of TIIP, which is possibly mediated by a Ca2+-protein kinase C signaling mechanism. These results provide mechanistic information about peripheral ischemic nociception that may be useful for developing better therapeutic management of ischemic pain in patients with peripheral arterial disease. Perspective: The results of the current study demonstrate that peripheral administration of an ASICs blocker or P2X antagonist significantly suppress TIIP. Co-administration of submaximal doses of ASIC and P2X antagonists produced an even greater effect. These results implicate peripheral ASICs and P2X receptors in the maintenance of thrombus-induced ischemic pain.

Original languageEnglish (US)
Pages (from-to)718-727
Number of pages10
JournalJournal of Pain
Volume11
Issue number8
DOIs
StatePublished - 2010

Fingerprint

Acid Sensing Ion Channels
Hyperalgesia
Amiloride
Rodentia
Thrombosis
Acid Sensing Ion Channel Blockers
Pain
Peripheral Arterial Disease
Maintenance
Protein Kinase C
Ischemia
Nociception
Protein C Inhibitor
Egtazic Acid
Femoral Artery
Pain Management
Protein Kinase Inhibitors
Acidosis
Adenosine Triphosphate
pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid

Keywords

  • acid-sensing ion channel
  • mechanical allodynia
  • P2X receptor
  • Peripheral ischemia
  • tissue acidosis

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Neurology
  • Clinical Neurology
  • Medicine(all)

Cite this

Peripheral acid-sensing ion channels and P2X receptors contribute to mechanical allodynia in a rodent thrombus-induced ischemic pain model. / Seo, Hyoung Sig; Roh, Dae Hyun; Yoon, Seo Yeon; Kang, Suk Yun; Moon, Ji Young; Kim, Hyun Woo; Han, Ho Jae; Chung, Jin; Beitz, Alvin J.; Lee, Jang Hern.

In: Journal of Pain, Vol. 11, No. 8, 2010, p. 718-727.

Research output: Contribution to journalArticle

Seo, Hyoung Sig ; Roh, Dae Hyun ; Yoon, Seo Yeon ; Kang, Suk Yun ; Moon, Ji Young ; Kim, Hyun Woo ; Han, Ho Jae ; Chung, Jin ; Beitz, Alvin J. ; Lee, Jang Hern. / Peripheral acid-sensing ion channels and P2X receptors contribute to mechanical allodynia in a rodent thrombus-induced ischemic pain model. In: Journal of Pain. 2010 ; Vol. 11, No. 8. pp. 718-727.
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AU - Roh, Dae Hyun

AU - Yoon, Seo Yeon

AU - Kang, Suk Yun

AU - Moon, Ji Young

AU - Kim, Hyun Woo

AU - Han, Ho Jae

AU - Chung, Jin

AU - Beitz, Alvin J.

AU - Lee, Jang Hern

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