UMLS:C0022104 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0022104 (irritable bowel syndrome)
8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pelvic pain associated with menstruation, i.e., dysmenorrhea, is a chronic pelvic pain that not only interferes with a woman's wellbeing for a large part of her life but also often co-occurs with other chronic painful conditions such as interstitial cystitis and irritable bowel syndrome and others. Little has been known about mechanisms underlying these chronic pelvic pains. This paper reviews 37 years of research in my laboratory at Florida State University on such mechanisms. Our research, mostly on rats, has contributed to the following findings: (1) Female reproductive organs are innervated in a topographic fashion by afferents in the pelvic (vagina/cervix) and hypogastric (cervix/uterine horn) nerves. (2) The input contributes to uterine and vaginal perceptions (nociception) that are modified by reproductive status. (3) Throughout the CNS, neurons responsive to stimulation of the reproductive tract also respond to stimulation of skin and other internal organs, in a manner modifiable by reproductive status and peripheral pathophysiology. (4) This dynamic physiological convergence may reflect extensive anatomical divergence of and interconnections between pathways entering the CNS via gateways through the spinal cord, dorsal column nuclei, and solitary nucleus. (5) The convergence also indicates the existence of extensive cross-system, viscero-visceral interactions within the CNS, that, while organized for coherent bodily functioning, serves as a substrate by which pathophysiology in one organ can influence physiology and responses to pathophysiology in other organs. (6) Some cross-system effects observed so far include: (a) Bladder inflammation reduces the rate of uterine contractions and the effects of drugs on the uterus. (b) Colon inflammation produces signs of inflammation in the otherwise healthy bladder and uterus. (c) A surgical model of endometriosis produces vaginal hyperalgesia, exacerbates pain behaviors induced by a ureteral stone, and reduces volume voiding thresholds if the bladder. These cross-system effects, which likely involve CNS mechanisms, likely also underlie co-occurrence of painful clinical conditions. Research continues on details of these mechanisms and their relevance for clinical diagnosis and therapy. None of this work could have been done without collegial support of colleagues and technical staff at Florida State University.
...
PMID:A life of pelvic pain. 1613 51

Chronic muscle pain (myalgia) is a common problem throughout the world. Seemingly simple, it is actually a difficult problem for the clinician interested in determining the aetiology of the pain, as well as in managing the pain. The two common muscle pain conditions are fibromyalgia and myofascial pain syndrome. Fibromyalgia is a chronic, widespread muscle tenderness syndrome, associated with central sensitisation. It is often accompanied by chronic sleep disturbance and fatigue, visceral pain syndromes like irritable bowel syndrome and interstitial cystitis. Myofascial pain syndrome is an overuse or muscle stress syndrome characterised by the presence of trigger points in muscle. The problem these syndromes pose lies not in making the diagnosis of muscle pain. Rather, it is the need to identify the underlying cause(s) of persistent or chronic muscle pain in order to develop a specific treatment plan. Chronic myalgia may not improve until the underlying precipitating or perpetuating factor(s) are themselves managed. Precipitating or perpetuating causes of chronic myalgia include structural or mechanical causes like scoliosis, localised joint hypomobility, or generalised or local joint laxity; and metabolic factors like depleted tissue iron stores, hypothyroidism or Vitamin D deficiency. Sometimes, correction of an underlying cause of myalgia is all that is needed to resolve the condition.
...
PMID:A review of myofascial pain and fibromyalgia--factors that promote their persistence. 1625 10

Fibromyalgia (FMS) is a debilitating disorder characterized by chronic diffuse muscle pain, fatigue, sleep disturbance, depression and skin sensitivity. There are no genetic or biochemical markers and patients often present with other comorbid diseases, such as migraines, interstitial cystitis and irritable bowel syndrome. Diagnosis includes the presence of 11/18 trigger points, but many patients with early symptoms might not fit this definition. Pathogenesis is still unknown, but there has been evidence of increased corticotropin-releasing hormone (CRH) and substance P (SP) in the CSF of FMS patients, as well as increased SP, IL-6 and IL-8 in their serum. Increased numbers of activated mast cells were also noted in skin biopsies. The hypothesis is put forward that FMS is a neuro-immunoendocrine disorder where increased release of CRH and SP from neurons in specific muscle sites triggers local mast cells to release proinflammatory and neurosensitizing molecules. There is no curative treatment although low doses of tricyclic antidepressants and the serotonin-3 receptor antagonist tropisetron, are helpful. Recent nutraceutical formulations containing the natural anti-inflammatory and mast cell inhibitory flavonoid quercetin hold promise since they can be used together with other treatment modalities.
...
PMID:Fibromyalgia--new concepts of pathogenesis and treatment. 1656 42

Somatic symptoms are common in primary care and clinicians often prescribe antidepressants as adjunctive therapy. There are many possible reasons why this may work, including treating comorbid depression or anxiety, inhibition of ascending pain pathways, inhibition of prefrontal cortical areas that are responsible for "attention" to noxious stimuli, and the direct effects of the medications on the syndrome. There are good theoretical reasons why antidepressants with balanced norepinephrine and serotonin effects may be more effective than those that act predominantly on one pathway, though head-to-head comparisons are lacking. For the 11 painful syndromes review in this article, cognitive-behavioral therapy is most consistently demonstrated to be effective, with various antidepressants having more or less randomized controlled data supporting or refuting effectiveness. This article reviews the randomized controlled trial data for the use of antidepressant and cognitive-behavior therapy for 11 somatic syndromes: irritable bowel syndrome, chronic back pain, headache, fibromyalgia, chronic fatigue syndrome, tinnitus, menopausal symptoms, chronic facial pain, noncardiac chest pain, interstitial cystitis, and chronic pelvic pain. For some syndromes, the data for or against treatment effectiveness is relatively robust, for many, however, the data, one way or the other is scanty.
...
PMID:Antidepressants and cognitive-behavioral therapy for symptom syndromes. 1657 78

Irritable bowel syndrome and interstitial cystitis frequently overlap. We have shown that acute colitis sensitizes urinary bladder afferents to both mechanical and chemical stimuli and that chronic colitis similarly produces neurogenic cystitis. We hypothesize that chronic irritation of the colon releases neuropeptides from bladder afferents, leading to receptor sensitization and neurogenic inflammation. Female Sprague-Dawley rats received intrarectal trinitrobenzenesulfonic acid (TNBS) or vehicle 3 days following either systemic capsaicin (CP) pretreatment or vehicle. Ten days later, action potentials of single-unit pelvic C-fiber afferents with receptive fields in the bladder were recorded under urethane anesthesia during graded bladder distensions (UBD) or intravesical capsaicin (vCP) administration. In controls, UBD increased bladder afferent firing in proportion to intravesical pressure. At intravesical pressures of 30 mmHg and above, the percent increase in afferent firing was significantly accentuated following TNBS compared with controls (1,222 +/- 176 vs. 624 +/- 54%, P < 0.01). The response to vCP was also enhanced (4,126 +/- 775 vs. 1,979 +/- 438%, P < 0.01). Systemic depletion of neuropeptides from sensory nerves abolished these effects. Histological examination of the bladders revealed an increase in mast cell density in TNBS-treated animals compared with controls (18.02 +/- 1.25 vs. 3.11 +/- 0.27 mast cells/x100 field, P < 0.01). This effect was significantly ameliorated with CP (10.25 +/- 0.95, P < 0.5 vs. TNBS-treated animals). In summary, chronic colonic irritation in the rat sensitizes urinary bladder afferents to noxious stimuli and causes mast cell infiltration in the bladder. Depletion of neuropeptides from sensory afferents diminishes these effects, suggesting they play an important role.
...
PMID:Sensitization of pelvic nerve afferents and mast cell infiltration in the urinary bladder following chronic colonic irritation is mediated by neuropeptides. 1692 45

Clinical studies reveal concomitant occurrence of several gastrointestinal and urologic disorders, including irritable bowel syndrome and interstitial cystitis. The purpose of this study was to determine the mechanisms underlying cross-organ sensitization at the level of dorsal root ganglion (DRG) after acute and subsided gastrointestinal inflammation. DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate) and Fast Blue were injected into the distal colon and urinary bladder of male rats, respectively. Convergent DRG neurons were found in L1-L3 and L6-S2 ganglia with an average distribution of 14% +/- 2%. The resting membrane potential (RMP) of cells isolated from upper lumbar (UL) ganglia was -59.8 +/- 2.7 mV, whereas lumbosacral (LS) neurons were more depolarized (RMP = -49.4 +/- 2.1 mV, P < or = 0.05) under control conditions. Acute trinitrobenzene sulfonic acid (TNBS) colitis (3 days) decreased voltage and current thresholds for action potential firing in LS but not UL convergent capsaicin-sensitive neurons. This effect persisted for 30 days in the absence of overt colonic inflammation. The current threshold for action potential (AP) firing in UL cells was also decreased from 165.0 +/- 24.5 pA (control) to 85.0 +/- 19.1 pA at 30 days (P < or = 0.05), indicating increased excitability. The presence of a subpopulation of colon-bladder convergent DRG neurons and their persistent hyperexcitability after colonic inflammation provides a basis for pelvic organ cross-sensitization.
...
PMID:Hyperexcitability of convergent colon and bladder dorsal root ganglion neurons after colonic inflammation: mechanism for pelvic organ cross-talk. 1696 97

Mast cells are involved in allergic reactions, where they secrete numerous vasoactive, inflammatory and nociceptive mediators in response to immunoglobulin E (IgE) and antigen. However, they have also been implicated in inflammatory conditions, such as painful bladder syndrome/interstitial cystitis (PBS/IC), irritable bowel syndrome (IBS) and migraines, all of which occur more often in women and are exacerbated during ovulation, but are suppressed during pregnancy. Mast cells express high affinity estrogen receptors and estradiol augments their secretion, while tamoxifen inhibits it. Here we report that progesterone (100 nM), but not the structurally related cholesterol, inhibits histamine secretion from purified rat peritoneal mast cells stimulated immunologically or by substance P (SP), an effect also documented by electron microscopy. These results suggest that mast cell secretion may be regulated by progesterone and may explain the reduced symptoms of certain inflammatory conditions during pregnancy.
...
PMID:Progesterone inhibits mast cell secretion. 1716

Painful bladder syndrome/interstitial cystitis (PBS/IC) is a disease of unknown aetiology, characterised by severe pressure and pain in the bladder area or lower pelvis that is frequently or typically relieved by voiding, along with urgency or frequency of urination in the absence of urinary tract infections. PBS/IC occurs primarily in women, is increasingly recognised in young adults, and may affect as many as 0.1-1% of adult women. PBS/IC is often comorbid with allergies, endometriosis, fibromyalgia, irritable bowel syndrome and panic syndrome, all of which are worsened by stress. As a result, patients may visit as many as five physicians, including family practitioners, internists, gynaecologists, urologists and pain specialists, leading to confusion and frustration. There is no curative treatment; intravesical dimethyl sulfoxide, as well as oral amitriptyline, pentosan polysulfate and hydroxyzine have variable results, with success more likely when these drugs are given together. Pilot clinical trials suggest that the flavonoid quercetin may be helpful. Lack of early diagnosis and treatment can affect outcomes and leads to the development of hyperalgesia/allodynia.
...
PMID:Treatment approaches for painful bladder syndrome/interstitial cystitis. 1728 85

Limbic associated pelvic pain is a proposed pathophysiology designed to explain features commonly encountered in patients with chronic pelvic pain, including the presence of multiple pain diagnoses, the frequency of previous abuse, the minimal or discordant pathologic changes of the involved organs, the paradoxical effectiveness of many treatments, and the recurrent nature of the condition. These conditions include endometriosis, interstitial cystitis, irritable bowel syndrome, levator ani syndrome, pelvic floor tension myalgia, vulvar vestibulitis, and vulvodynia. The hypothesis is based on recent improvements in the understanding of pain processing pathways in the central nervous system, and in particular the role of limbic structures, especially the anterior cingulate cortex, hippocampus and amygdala, in chronic and affective pain perception. Limbic associated pelvic pain is hypothesized to occur in patients with chronic pelvic pain out of proportion to any demonstrable pathology (hyperalgesia), and with more than one demonstrable pain generator (allodynia), and who are susceptible to development of the syndrome. This most likely occurs as a result of childhood sexual abuse but may include other painful pelvic events or stressors, which lead to limbic dysfunction. This limbic dysfunction is manifest both as an increased sensitivity to pain afferents from pelvic organs, and as an abnormal efferent innervation of pelvic musculature, both visceral and somatic. The pelvic musculature undergoes tonic contraction as a result of limbic efferent stimulation, which produces the minimal changes found on pathological examination, and generates a further sensation of pain. The pain afferents from these pelvic organs then follow the medial pain pathway back to the sensitized, hypervigilant limbic system. Chronic stimulation of the limbic system by pelvic pain afferents again produces an efferent contraction of the pelvic muscles, thus perpetuating the cycle. This cycle is susceptible to disruption through blocking afferent signals from pelvic organs, either through anesthesia or muscle manipulation. Disruption of limbic perception with psychiatric medication similarly produces relief. Without a full disruption of both the central hypervigilance and pelvic organ dysfunction, pain recurs. To prevent recurrence, clinicians will need to include some form of therapy, either medical or cognitive, targeted at the underlying limbic hypervigilance. Further research into novel, limbic targeted therapies can hopefully be stimulated by explicitly stating the role of the limbic system in chronic pain. This hypothesis provides a framework for clinicians to rationally approach some of the most challenging patients in medicine, and can potentially improve outcomes by including management of limbic dysfunction in their treatment.
...
PMID:Limbic associated pelvic pain: a hypothesis to explain the diagnostic relationships and features of patients with chronic pelvic pain. 1729 60

Visceral organ "cross talk" is suspected to contribute to multiorgan symptomatology found in conditions such as irritable bowel syndrome and interstitial cystitis. The goal of the present study was to investigate the short- and long-term effects of acute colitis on bladder detrusor muscle contractility. We hypothesized that inflammation of the colon leads to changes in bladder function via direct changes in detrusor smooth muscle contractility. In this study, colonic inflammation was induced in male rats via an enema of trinitrobenzenesulfonic acid (TNBS) (50 mg/kg, 0.5 ml, 25% ethanol). Colitis was confirmed using gross morphology, histology, and measurements of myeloperoxidase activity. Saline enema-treated rats served as controls. Three, 15, and 30 days postenema treatment, bladder detrusor muscle contractility was investigated in response to electrical field stimulation (EFS), cholinergic agonism with carbachol (CCh), and KCl. During active colonic inflammation (day 3 post-TNBS enema), the bladder detrusor muscle appeared normal and showed no significant inflammation. However, abnormalities in bladder detrusor muscle contractility occurred in response to EFS and CCh but not KCl. During and after recovery from colonic inflammation (days 15 and 30 post-TNBS enema), changes in bladder detrusor muscle contractility in response to EFS and CCh returned to control levels. We found that a transient colonic inflammatory insult significantly attenuates the amplitude of bladder detrusor muscle contractions in vitro, at least in part, through changes in cholinergic innervation, which are reversible after recovery from the colitis.
...
PMID:Changes in urinary bladder smooth muscle function in response to colonic inflammation. 1771 61

<< Previous 1 2 3 4 5 6 7 8 Next >>