Markedly attenuated acute and chronic pain responses in mice lacking adenylyl cyclase-5

K. S. Kim, Junesun Kim, S. K. Back, J. Y. Im, Heung Sik Na, P. L. Han

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Chronic inflammatory and neuropathic pain is often difficult to manage using conventional remedies. The underlying mechanisms and therapeutic strategies required for the management of chronic pain need to be urgently established. The cyclic AMP (cAMP) second messenger system has been implicated in the mechanism of nociception, and the inhibition of the cAMP pathway by blocking the activities of adenylyl cyclase (AC) and protein kinase A has been found to prevent chronic pain in animal models. However, little is known regarding which of the 10 known isoforms of AC are involved in nociceptive pathways. Therefore, we investigated the potential pronociceptive function of AC5 in nociception using recently developed AC5 knockout mice (AC5 -/-). We found that AC5-/- mice show markedly attenuated pain-like responses in acute thermal and mechanical pain tests as compared with the wildtype control. Also, AC5-/- mice display hypoalgesic responses to inflammatory pain induced by subcutaneous formalin injection into hindpaws, and to non-inflammatory and inflammatory visceral pain induced by injecting magnesium sulfate or acetic acid into the abdomen. Moreover, AC5-/- mice show strongly suppressed mechanical and thermal allodynia in two nerve injury-induced neuropathic pain models. These results suggest that AC5 is essential for acute and chronic pain, and that AC5 knockout mice provide a useful model for the evaluation of the pathophysiological mechanisms of pain.

Original languageEnglish
Pages (from-to)120-127
Number of pages8
JournalGenes, Brain and Behavior
Volume6
Issue number2
DOIs
Publication statusPublished - 2007 Mar 1

Fingerprint

Acute Pain
Chronic Pain
Pain
Nociception
Hyperalgesia
Neuralgia
Adenylyl Cyclases
Knockout Mice
Cyclic AMP
Visceral Pain
Magnesium Sulfate
Second Messenger Systems
Subcutaneous Injections
Cyclic AMP-Dependent Protein Kinases
Acetic Acid
Abdomen
Formaldehyde
Protein Isoforms
Animal Models
Hot Temperature

Keywords

  • Adenylyl cyclase
  • cAMP
  • Inflammatory pain
  • Neuropathic pain
  • Nociception

ASJC Scopus subject areas

  • Neuroscience(all)
  • Genetics

Cite this

Markedly attenuated acute and chronic pain responses in mice lacking adenylyl cyclase-5. / Kim, K. S.; Kim, Junesun; Back, S. K.; Im, J. Y.; Na, Heung Sik; Han, P. L.

In: Genes, Brain and Behavior, Vol. 6, No. 2, 01.03.2007, p. 120-127.

Research output: Contribution to journalArticle

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