Colon mustard oil instillation induced cross-organ reflex sensitization on the pelvic-urethra reflex activity in rats.
We investigated the participation of cyclin-dependent kinase-5 (Cdk5)-mediated N-methyl-D-aspartate receptor (NMDAR) NR2B subunit phosphorylation in cross-organ reflex sensitization caused by colon irritation. The external urethral sphincter electromyogram (EUSE) reflex activity evoked by the pelvic afferent nerve test stimulation (TS, 1 stimulation/30s) and protein expression in the spinal cord and dorsal root ganglion tissue (T13-L2 and L6-S2 ipsilateral to the stimulation) in response to colon mustard oil (MO) instillation were tested in anesthetized rats. When compared with a baseline reflex activity with a single action potential evoked by the TS before the administration of test agents, MO instillation into the descending colon sensitized the evoked activity characterized by elongated firing in the reflex activity in association with increased protein levels of Cdk5, PSD95, and phosphorylated NR2B (pNR2B) but not of total NR2B (tNR2B) in the spinal cord tissue. Both cross-organ reflex sensitization and increments in protein expression were reversed by intra-colonic pretreatments with ruthenium red (a non-selective transient receptor potential vanilloid, TRPV, antagonist), capsaizepine (a TRPV1-selective antagonist), lidocaine (a nerve conduction blocker) as well as by the intra-thecal pretreatment with APV (a NRMDR antagonist) Co-101244 (a NR2B-selective antagonist) and roscovitine (a Cdk5 antagonist). Moreover, compared with the control group, both the increase in pNR2B and the cross-organ reflex sensitization were attenuated in the si-RNA of NR2B rats. All these results suggested that Cdk-dependent NMDAR NR2B subunit phosphorylation mediates the development of cross-organ pelvic-urethra reflex sensitization caused by acute colon irritation which could possibly underlie the high concurrence of pelvic pain syndrome with irritable bowel syndrome.
Peng
Hsien-Yu
HY
Department of Physiology, College of Medicine, Chung-Shan Medical University, No. 110, Chang-Kuo North Rd. Section 1, Taichung 40201, Taiwan.
Chen
Gin-Den
GD
Tung
Kwong-Chung
KC
Lai
Cheng-Yuan
CY
Hsien
Ming-Chun
MC
Chiu
Chun-Hsien
CH
Lu
Hsiao-Ting
HT
Liao
Jiuan-Miaw
JM
Lee
Shin-Da
SD
Lin
Tzer-Bin
TB
D000818:Animals; D003106:Colon / Q000166:cytology / Q000187:drug effects*; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism; D004558:Electric Stimulation; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D008297:Male; D009149:Mustard Plant / Q000009:adverse effects*; D010388:Pelvis / Q000294:innervation*; D010880:Piperidines / Q000494:pharmacology; D010938:Plant Oils / Q000009:adverse effects*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics; D012018:Reflex / Q000187:drug effects; D000077546:Roscovitine; D050916:TRPV Cation Channels / Q000378:metabolism; D014521:Urethra / Q000294:innervation*
D018683:Excitatory Amino Acid Agents; C121001:NR2B NMDA receptor; D010880:Piperidines; D010938:Plant Oils; D047428:Protein Kinase Inhibitors; D011687:Purines; D034741:RNA, Small Interfering; D016194:Receptors, N-Methyl-D-Aspartate; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D000077546:Roscovitine; D018698:Glutamic Acid; D051360:Cyclin-Dependent Kinase 5; C120799:PD 174494; C027793:mustard oil