title: P2X3 receptor-mediated visceral hyperalgesia and neuronal sensitization following exposure to PTSD-like stress in the dorsal root ganglia of rats.
abstract: BACKGROUND
  Patients with posttraumatic stress disorder (PTSD) often share co-morbidity with chronic pain conditions. Recent studies suggest a role of P2X3 receptors and ATP signaling in pain conditions. However, the underlying mechanisms of visceral hyperalgesia following exposure to PTSD-like stress conditions remain unclarified.
  
  
  METHODS
  The behavior and hormones relevant for PTSD were studied. Visceromotor responses (VMR) and the abdominal withdrawal reflexes (AWR) to colorectal distention (CRD) were recorded to determine P2X3-receptor-mediated alteration of hyperalgesia following single-prolonged stress (SPS) exposure. Immunofluorescence, Western blotting, and patch-clamp were used.
  
  
  RESULTS
  The escape latency, adrenocorticotropic hormone and cortisol were increased on days 7-14. Visceromotor responses and AWR was reduced at day 1 in SPS rats but increased to higher levels than in controls after exposure to day 7. Intrathecal administration of the P2X3-receptor antagonist TNP-ATP abolished the CRD response. Based on immunofluorescence and Western blotting analysis, SPS-treated rats exhibited reduced P2X3 expression in dorsal root ganglia (DRG) after day 1 compared with controls. P2X3 expression in DRG was enhanced on day 7 after SPS and the increase of the P2X3 expression was maintained on day 14 and 21 compared with controls. The P2X3-receptor agonist α,β-me ATP (10 μM) induced a fast desensitizing inward current in DRG neurons of both control and SPS-treated rats. The average peak current densities in SPS-treated group were increased 3.6-fold. TNP-ATP (100 nM) markedly blocked all fast α,β-me ATP-induced inward currents in the DRG neurons both in control and SPS-treated rats.
  
  
  CONCLUSIONS
  The data indicate an important role of P2X3 signaling in visceral hyperalgesia following PTSD-like stress.
authors: State Key Laboratory of Trauma, Burns and Combined Injury, Department of Gastroenterology, Daping Hospital, Third Military Medical University, Chongqing, China.
authors: Y-Q
authors: YQ
authors: He
authors: State Key Laboratory of Trauma, Burns and Combined Injury, Department of Gastroenterology, Daping Hospital, Third Military Medical University, Chongqing, China.
authors: X-Q
authors: XQ
authors: Lang
authors: State Key Laboratory of Trauma, Burns and Combined Injury, Department of Gastroenterology, Daping Hospital, Third Military Medical University, Chongqing, China.
authors: L
authors: L
authors: Lin
authors: State Key Laboratory of Trauma, Burns and Combined Injury, Department of Gastroenterology, Daping Hospital, Third Military Medical University, Chongqing, China.
authors: L
authors: L
authors: Ji
authors: Department of Gastroenterology, The Ninth People's Hospital of Chongqing, Chongqing, China.
authors: X-Y
authors: XY
authors: Yuan
authors: State Key Laboratory of Trauma, Burns and Combined Injury, Department of Gastroenterology, Daping Hospital, Third Military Medical University, Chongqing, China.
authors: Q
authors: Q
authors: Chen
authors: State Key Laboratory of Trauma, Burns and Combined Injury, Department of Gastroenterology, Daping Hospital, Third Military Medical University, Chongqing, China.
authors: Y-M
authors: YM
authors: Ran
authors: Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Chongqing, China.
authors: H-S
authors: HS
authors: Chen
authors: Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors: L
authors: L
authors: Li
authors: Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors: J-M
authors: JM
authors: Wang
authors: State Key Laboratory of Trauma, Burns and Combined Injury, Department of Gastroenterology, Daping Hospital, Third Military Medical University, Chongqing, China.|Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors: Z-G
authors: ZG
authors: Wang
authors: GIOME and the Key Laboratory for Biorheological Science and Technology of Ministry of Education, Bioengineering College of Chongqing University, Chongqing, China.
authors: H
authors: http://orcid.org/0000-0002-5792-2845
authors: H
authors: Gregersen
authors: Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors: D-W
authors: DW
authors: Zou
authors: State Key Laboratory of Trauma, Burns and Combined Injury, Department of Gastroenterology, Daping Hospital, Third Military Medical University, Chongqing, China.|Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors: H-P
authors: HP
authors: Liang
authors: State Key Laboratory of Trauma, Burns and Combined Injury, Department of Gastroenterology, Daping Hospital, Third Military Medical University, Chongqing, China.|Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors: M
authors: M
authors: Yang
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004924:Escape Reaction / Q000187:drug effects / Q000502:physiology; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology*; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology* / Q000523:psychology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D058911:Purinergic P2X Receptor Agonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D058477:Receptors, Purinergic P2X3 / Q000502:physiology*; D013313:Stress Disorders, Post-Traumatic / Q000150:complications / Q000503:physiopathology* / Q000523:psychology; D059265:Visceral Pain / Q000209:etiology / Q000503:physiopathology* / Q000523:psychology
chemical_list: D058911:Purinergic P2X Receptor Agonists; D058477:Receptors, Purinergic P2X3; C045674:2',3'-O-(2,4,6-trinitro-cyclohexadienylidine)adenosine 5'-triphosphate; D000255:Adenosine Triphosphate
keywords: dorsal root ganglion; patch clamp recording; posttraumatic stress disorder; purinergic P2X3; visceral hyperalgesia