Neonatal Maternal Deprivation Enhances Presynaptic P2X7 Receptor Transmission in Insular Cortex in an Adult Rat Model of Visceral Hypersensitivity

CNS Neurosci Ther. 2017 Feb;23(2):145-154. doi: 10.1111/cns.12663. Epub 2016 Dec 15.


Aims: Insular cortex (IC) is involved in processing the information of pain. The aim of this study was to investigate roles and mechanisms of P2X7 receptors (P2X7Rs) in IC in development of visceral hypersensitivity of adult rats with neonatal maternal deprivation (NMD).

Methods: Visceral hypersensitivity was quantified by abdominal withdrawal reflex threshold to colorectal distension (CRD). Expression of P2X7Rs was determined by qPCR and Western blot. Synaptic transmission in IC was recorded by patch-clamp recording.

Results: The expression of P2X7Rs and glutamatergic neurotransmission in IC was significantly increased in NMD rats when compared with age-matched controls. Application of BzATP (P2X7R agonist) enhanced the frequency of spontaneous excitatory postsynaptic currents (sEPSC) and miniature excitatory postsynaptic currents (mEPSC) in IC slices of control rats. Application of BBG (P2X7R antagonist) suppressed the frequencies of sEPSC and mEPSC in IC slices of NMD rats. Microinjection of BzATP into right IC significantly decreased CRD threshold in control rats while microinjection of BBG or A438079 into right IC greatly increased CRD threshold in NMD rats.

Conclusion: Data suggested that the enhanced activities of P2X7Rs in IC, likely through a presynaptic mechanism, contributed to visceral hypersensitivity of adult rats with NMD.

Keywords: Insular cortex; Neonatal maternal deprivation; Purinergic P2X receptors; Visceral pain.

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Adenosine Triphosphate / analogs & derivatives
  • Adenosine Triphosphate / pharmacology
  • Animals
  • Animals, Newborn
  • Cerebral Cortex / cytology*
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • In Vitro Techniques
  • Male
  • Maternal Deprivation*
  • Phosphopyruvate Hydratase / metabolism
  • Platelet Aggregation Inhibitors / pharmacology
  • Presynaptic Terminals / physiology*
  • Purinergic Agents / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Purinergic P2X7 / metabolism*
  • Synaptophysin / metabolism
  • Up-Regulation / drug effects
  • Up-Regulation / physiology
  • Visceral Pain / pathology*


  • Excitatory Amino Acid Antagonists
  • Platelet Aggregation Inhibitors
  • Purinergic Agents
  • Receptors, Purinergic P2X7
  • Synaptophysin
  • 3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • 2-Amino-5-phosphonovalerate
  • Adenosine Triphosphate
  • Phosphopyruvate Hydratase