Organ cross talk modulates pelvic pain

Abstract

(IC) is a chronic bladder inflammatory disease of unknown etiology that is often regarded as a neurogenic cystitis. IC is associated with urothelial lesions, voiding dysfunction, and pain in the pelvic/perineal area, and diet can exacerbate IC symptoms. In this study, we used a murine neurogenic cystitis model to investigate the development of pelvic pain behavior. Neurogenic cystitis was induced by the injection of Bartha's strain of pseudorabies virus (PRV) into the abductor caudalis dorsalis tail base muscle of female C57BL/6J mice. Infectious PRV virions were isolated only from the spinal cord, confirming the centrally mediated nature of this neurogenic cystitis model. Pelvic pain was assessed using von Frey filament stimulation to the pelvic region, and mice infected with PRV developed progressive pelvic pain. Pelvic pain was alleviated by 2% lidocaine instillation into either the bladder or the colon but not following lidocaine instillation into the uterus. The bladders of PRV-infected mice showed markers of inflammation and increased vascular permeability compared with controls. In contrast, colon histology was normal and vascular permeability was unchanged, suggesting that development of pelvic pain was due only to bladder inflammation. Bladder-induced pelvic pain was also exacerbated by colonic administration of a subthreshold dose of capsaicin. These data indicate organ cross talk in pelvic pain and modulation of pain responses by visceral inputs distinct from the inflamed site. Furthermore, these data suggest a mechanism by which dietary modification benefits pelvic pain symptoms.bladder; interstitial cystitis; diet INTERSTITIAL CYSTITIS (IC), also known as painful bladder syndrome, is a chronic bladder inflammatory disease with unknown etiology that afflicts as many as 1 million patients in the United States, with females comprising ϳ90% of patients (21). Symptoms of IC include pelvic and/or perineal pain, urinary frequency, urgency, and nocturia (17,20,32,39). IC is often regarded as a neurogenic cystitis due to voiding dysfunction and the partial efficacy of sacral nerve stimulation or neuropharmacological therapies in some patients that suggests a neuronal component. Supporting this idea, cats are susceptible to feline IC, a disease that closely mimics human IC and is associated with increased activity in the sympathetic nervous system (40). Since IC symptoms can flare in response to certain foods (e.g., tomatoes), dietary modification is commonly employed by IC patients, although evidence of altered urine properties as the mechanism for dietary effects is lacking.One model of IC pathogenesis involves a positive feedback loop, whereby substance P-containing peripheral nerves stimulate mast cells, in turn releasing inflammatory mediators that induce urothelial inflammation (15). Furthermore, histamine release by mast cells feeds back onto peripheral nerves to cause sustained release of substance P and mast cell activation. Consistent with this model, patients with IC show elevated mast cell counts ...

Overexpression of NGF in mouse urothelium leads to neuronal hyperinnervation, pelvic sensitivity, and changes in urinary bladder function

“…Referred (secondary) hyperalgesia and tactile allodynia were measured using calibrated von Frey hairs with forces of 0.04, 0.16, 0.4, 1, and 4 g applied to the abdomen (53,54,90) and hindpaw (11,34,90). Mice were tested in individual Plexiglas chambers with a stainless-steel wire grid floor.…”

“…Testing of the plantar region of the hindpaw and lower abdominal area was performed by perpendicular application of von Frey hairs to the indicated areas until the hair bent slightly. The following behaviors were considered positive responses to pelvic region stimulation: sharp retraction of the abdomen, jumping, or immediate licking or scratching of the pelvic area (90). A positive response to hindpaw stimulation was sharp withdrawal of the paw or licking of the tested hindpaw (90).…”

“…The following behaviors were considered positive responses to pelvic region stimulation: sharp retraction of the abdomen, jumping, or immediate licking or scratching of the pelvic area (90). A positive response to hindpaw stimulation was sharp withdrawal of the paw or licking of the tested hindpaw (90). All somatic testing was performed in a blinded manner with respect to treatment and mouse strain.…”

Beyond a Simple Anesthetic Effect: Lidocaine in the Diagnosis and Treatment of Interstitial Cystitis/bladder Pain Syndrome

“…[4][5][6] Far more common than classic IC with mucosal ulceration is BPS, with inconsistent clinical and bladder findings, except for a strong association with fibromyalgia and irritable bowel syndrome. 7 This may represent a disease entity having a primary source elsewhere, such as myofascial pain, 8,9 with the colocated spinal cord dorsal horn instigating bladder symptoms via complex and powerful mechanisms, which we now understand as peripheral and central sensitization. 10 Lidocaine is a common local anesthetic (LA) agent that is also used in a variety of chronic and persistent pain syndromes, including treatment of IC/BPS.…”

Novel spinal pathways identified by neuronal c-Fos expression after urethrogenital reflex activation in female guinea pigs

“…Anatomically, there is a considerable degree of overlap and interaction between neural pathways to different pelvic organs (eg. rectum and urogenital system) with considerable potential for integration or modulation of their activity within the spinal cord (Berkley, 2006;Pezzone et al, 2005;Rudick et al, 2007;Ustinova et al, 2006;Ustinova et al, 2010).…”