title: Activation of p38 MAPK in the rostral ventromedial medulla by visceral noxious inputs transmitted via the dorsal columns may contribute to pelvic organ cross-sensitization in rats with endometriosis.
abstract: Whether visceral organ cross-sensitization is involved in endometriosis-associated pain remains elusive. Previous studies have shown that visceral noxious stimuli may trigger a cascade of signal transductions in the rostral ventromedial medulla (RVM) via the spinal dorsal column (DC) pathway and the RVM plays a critical role in the descending control of visceral nociception. In the current study, we hypothesized that the p38 mitogen-activated protein kinase (MAPK) activation in the RVM by noxious visceral inputs from ectopic growths via the DC was involved in the development of pelvic organ cross-sensitization in established endometriosis. A rat model of experimental endometriosis was established. To examine ectopic growths-to-colon cross-sensitization, graded colorectal distention (CRD) was performed and abdominal withdrawal reflex (AWR) scores were recorded in female rats at 8weeks after the uterine or fat (control) auto-transplantation. Western blot study was carried out to examine the phosphorylated form and the total level of p38 MAPK protein in the RVM. Our results showed that lesions of bilateral DCs immediately following uterine or fat auto-transplantation in female rats significantly attenuated the later development of ectopic growths-to-colon cross-sensitization and the increased p38 MAPK activation in the RVM, as compared to sham DC lesions. Furthermore, intra-RVM microinjection of a p38 MAPK inhibitor (SB 203580), but not vehicle, in female rats with established endometriosis significantly attenuated ectopic growths-to-colon cross-sensitization and the increased activation of p38 MAPK in the RVM. These findings suggest that the noxious inputs from ectopic growths may activate p38 MAPK in the RVM via the DC, which may contribute to the development of ectopic growths-to-colon cross-sensitization in established endometriosis.
authors.affiliation: Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China; Department of Anesthesiology, Affiliated Hospital, Guilin Medical University, Guilin, Guangxi Province 541000, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: F
authors.initials: F
authors.lastname: Xie
authors.affiliation: Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: M
authors.initials: M
authors.lastname: Bao
authors.affiliation: Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Chao
authors.affiliation: Department of Anesthesiology, Affiliated Hospital, Guilin Medical University, Guilin, Guangxi Province 541000, China.
authors.forename: C
authors.initials: C
authors.lastname: Lin
authors.affiliation: Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: R
authors.initials: R
authors.lastname: Guo
authors.affiliation: Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: C
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: A
authors.initials: A
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Yue
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China. Electronic address: sincerewy@yahoo.com.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000273:Adipose Tissue / Q000637:transplantation; D000818:Animals; D003106:Colon / Q000201:enzymology*; D004195:Disease Models, Animal; D004715:Endometriosis / Q000201:enzymology*; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D008526:Medulla Oblongata / Q000187:drug effects / Q000201:enzymology*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D010812:Physical Stimulation; D011312:Pressure; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D066148:Spinal Cord Dorsal Horn / Q000201:enzymology; D014182:Transplantation, Autologous; D014599:Uterus / Q000637:transplantation; D059265:Visceral Pain / Q000188:drug therapy / Q000201:enzymology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580
keywords: dorsal column; endometriosis; rostral ventromedial medulla; visceral hyperalgesia