Inflammation in the uterus induces phosphorylated extracellular signal-regulated kinase and substance P immunoreactivity in dorsal root ganglia neurons innervating both uterus and colon in rats.
In women, clinical studies suggest that pain syndromes such as irritable bowel syndrome and interstitial cystitis, which are associated with visceral hyperalgesia, are often comorbid with endometriosis and chronic pelvic pain. One of the possible explanations for this phenomenon is viscerovisceral cross-sensitization, in which increased nociceptive input from an inflamed pelvic organ sensitizes neurons that receive convergent input to the same dorsal root ganglion (DRG) from an unaffected visceral organ. Nociception induces up-regulation of cellular mechanisms such as phosphorylated extracellular signal-regulated kinase (pERK) and substance P (SP), neurotransmitters associated with induced pain sensation. The purpose of this study was to determine, in a rodent model, whether uterine inflammation increased the number of pERK- and SP-positive neurons that received input from both the uterus and the colon. Cell bodies of colonic and uterine DRG were retrogradely labeled with fluorescent tracer dyes microinjected into the colon/rectum and into the uterus. Ganglia were harvested for fluorescent microscopy to identify positively stained neurons. Approximately 6% of neurons were colon specific and 10% uterus specific. Among these uterus- or colon-specific neurons, up to 3-5% of DRG neurons in the lumbosacral neurons (L1-S3 levels) received input from both visceral organs. Uterine inflammation increased the number of pERK- and SP-immunoreactive DRG neurons innervating specifically colon, or innervating specifically uterus, and those innervating both organs. These results suggest that a localized inflammation activates primary visceral afferents, regardless of whether they innervate the affected organ. This visceral sensory integration in the DRG may underlie the observed comorbidity of female pelvic pain syndromes.
Li
Jichang
J
Department of Anesthesiology, Harbor-UCLA Medical Center, Los Angeles, California, USA.
Micevych
Paul
P
McDonald
John
J
Rapkin
Andrea
A
Chaban
Victor
V
D000818:Animals; D003106:Colon / Q000294:innervation* / Q000378:metabolism; D004790:Enzyme Induction / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis* / Q000378:metabolism; D005260:Female; D005727:Ganglia, Spinal / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism*; D009474:Neurons / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D051381:Rats; D020318:Rats, Long-Evans; D013373:Substance P / Q000096:biosynthesis* / Q000378:metabolism; D014599:Uterus / Q000294:innervation* / Q000473:pathology*
D018836:Inflammation Mediators; D013373:Substance P; D048049:Extracellular Signal-Regulated MAP Kinases