P2X3 receptor-mediated visceral hyperalgesia and neuronal sensitization following exposure to PTSD-like stress in the dorsal root ganglia of rats

被引：22

作者：

He, Y. -Q. ^{[1
]}

Lang, X. -Q. ^{[1
]}

Lin, L. ^{[1
]}

Ji, L. ^{[1
]}

Yuan, X. -Y. ^{[2
]}

Chen, Q. ^{[1
]}

Ran, Y. -M. ^{[1
]}

Chen, H. -S. ^{[3
]}

Li, L. ^{[4
]}

Wang, J. -M. ^{[4
]}

Wang, Z. -G. ^{[1
,4
]}

Gregersen, H. ^{[5
,6
]}

Zou, D. -W. ^{[7
]}

Liang, H. -P. ^{[1
,4
]}

Yang, M. ^{[1
,4
]}

机构：

[1] Third Mil Med Univ, Daping Hosp, Dept Gastroenterol, State Key Lab Trauma Burns & Combined Injury, Chongqing, Peoples R China

[2] Ninth Peoples Hosp Chongqing, Dept Gastroenterol, Chongqing, Peoples R China

[3] Chongqing Key Lab Translat Med Res Cognit Dev & L, Chongqing, Peoples R China

[4] Third Mil Med Univ, Daping Hosp, Res Inst Surg, Chongqing, Peoples R China

[5] Chongqing Univ, Bioengn Coll, Minist Educ, GIOME, Chongqing, Peoples R China

[6] Chongqing Univ, Bioengn Coll, Minist Educ, Key Lab Biorheol Sci & Technol, Chongqing, Peoples R China

[7] Second Mil Med Univ, Changhai Hosp, Dept Gastroenterol, Shanghai, Peoples R China

来源：

NEUROGASTROENTEROLOGY AND MOTILITY | 2017年 / 29卷 / 03期

关键词：

dorsal root ganglion; patch clamp recording; posttraumatic stress disorder; purinergic P2X3; visceral hyperalgesia; IRRITABLE-BOWEL-SYNDROME; FUNCTIONAL UP-REGULATION; CHRONIC PAIN; ANIMAL-MODELS; MECHANOSENSORY TRANSDUCTION; MECHANICAL HYPERALGESIA; P2X(3) EXPRESSION; INDUCED ANALGESIA; NEUROPATHIC PAIN; SEX-DIFFERENCES;

D O I：

10.1111/nmo.12976

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

BackgroundPatients 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. MethodsThe 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 ResultsThe 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 ,-me ATP (10M) 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 (100nM) markedly blocked all fast ,-me ATP-induced inward currents in the DRG neurons both in control and SPS-treated rats. Conclusions & InferencesThe data indicate an important role of P2X3 signaling in visceral hyperalgesia following PTSD-like stress.

引用

页数：15

共 80 条

[1] The Glt1 glutamate receptor mediates the establishment and perpetuation of chronic visceral pain in an animal model of stress-induced bladder hyperalgesia [J].