Inhibition of the cAMP/PKA/CREB Pathway Contributes to the Analgesic Effects of Electroacupuncture in the Anterior Cingulate Cortex in a Rat Pain Memory Model

Neural Plast. 2016:2016:5320641. doi: 10.1155/2016/5320641. Epub 2016 Dec 20.

Abstract

Pain memory is considered as endopathic factor underlying stubborn chronic pain. Our previous study demonstrated that electroacupuncture (EA) can alleviate retrieval of pain memory. This study was designed to observe the different effects between EA and indomethacin (a kind of nonsteroid anti-inflammatory drugs, NSAIDs) in a rat pain memory model. To explore the critical role of protein kinase A (PKA) in pain memory, a PKA inhibitor was microinjected into anterior cingulate cortex (ACC) in model rats. We further investigated the roles of the cyclic adenosine monophosphate (cAMP), PKA, cAMP response element-binding protein (CREB), and cAMP/PKA/CREB pathway in pain memory to explore the potential molecular mechanism. The results showed that EA alleviates the retrieval of pain memory while indomethacin failed. Intra-ACC microinjection of a PKA inhibitor blocked the occurrence of pain memory. EA reduced the activation of cAMP, PKA, and CREB and the coexpression levels of cAMP/PKA and PKA/CREB in the ACC of pain memory model rats, but indomethacin failed. The present findings identified a critical role of PKA in ACC in retrieval of pain memory. We propose that the proper mechanism of EA on pain memory is possibly due to the partial inhibition of cAMP/PKA/CREB signaling pathway by EA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesia / methods
  • Animals
  • Cyclic AMP / biosynthesis*
  • Cyclic AMP Response Element-Binding Protein / biosynthesis*
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic AMP-Dependent Protein Kinases / biosynthesis*
  • Disease Models, Animal
  • Electroacupuncture / methods*
  • Gyrus Cinguli / drug effects
  • Gyrus Cinguli / metabolism*
  • Indomethacin / administration & dosage
  • Injections, Intraventricular
  • Male
  • Memory / drug effects
  • Memory / physiology
  • Pain / drug therapy
  • Pain / metabolism*
  • Pain Measurement / drug effects
  • Pain Measurement / methods
  • Protein Kinase Inhibitors / administration & dosage
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Treatment Outcome

Substances

  • Cyclic AMP Response Element-Binding Protein
  • Protein Kinase Inhibitors
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Indomethacin