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- Title
P2X3 receptor-mediated visceral hyperalgesia and neuronal sensitization following exposure to PTSD-like stress in the dorsal root ganglia of rats.
- Authors
He, Y.‐Q.; Lang, X.‐Q.; Lin, L.; Ji, L.; Yuan, X.‐Y.; Chen, Q.; Ran, Y.‐M.; Chen, H.‐S.; Li, L.; Wang, J.‐M.; Wang, Z.‐G.; Gregersen, H.; Zou, D.‐W.; Liang, H.‐P.; Yang, M.
- 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. Key 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 & Inferences The data indicate an important role of P2X3 signaling in visceral hyperalgesia following PTSD-like stress.
- Subjects
POST-traumatic stress disorder; DISEASES; CHRONIC pain; IMMUNOFLUORESCENCE; WESTERN immunoblotting
- Publication
Neurogastroenterology & Motility, 2017, Vol 29, Issue 3, pn/a
- ISSN
1350-1925
- Publication type
Article
- DOI
10.1111/nmo.12976