Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aquaporins (AQP) are a family of at least ten homologous water transporting proteins in mammals that are expressed in many epithelial, endothelial and other tissues. Abnormalities in humans and mice lacking AQPs provide direct evidence for their physiological importance. Humans lacking AQP1 or AQP2 manifest polyuria with defective urinary concentrating ability and humans with mutations in MIP (AQP0) develop cataracts. Transgenic knockout mice lacking AQP1 or AQP3 are also remarkably polyuric, and knock-in mice expressing a mutant AQP2 have severe nephrogenic diabetes insipidus resulting in impaired neonatal survival. Other interesting phenotypes in AQP knockout mice include reduced pain sensation, reduced intraocular pressure, defective corneal fluid transport and impaired dietary fat processing (AQP1), dry skin (AQP3), protection from brain swelling and impaired hearing/vision (AQP4), and reduced fluid secretion by salivary and airway submucosal glands (AQP5). However, many phenotype studies were negative, such as normal airway/lung and skeletal muscle function despite AQP expression, indicating that tissue-specific aquaporin expression does not indicate physiological significance. The general paradigm from studies on transgenic mouse models of AQP deletion is that AQPs facilitate rapid near-isosmolar transepithelial fluid absorption / secretion, as well as rapid vectorial water movement driven by osmotic gradients. The transgenic mouse studies suggest that aquaporin inhibitors may have clinical indications as diuretics and in the treatment of cerebral edema, elevated intraocular pressure, and other conditions of abnormal fluid homeostasis.
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PMID:Physiological importance of aquaporin water channels. 1217 89

Aquaporin 1 (AQP1) is the archetypal member of a family of water channel proteins that contribute to water homeostasis in kidney, lung, and other tissues. Although there is limited evidence that aquaporins are expressed in the nervous system, AQP4 is expressed in glia and AQP9 is present on some neuronal and glial mitochondria. In the present study, we used immunohistochemistry to show that AQP1 is heavily expressed in a population of small diameter primary sensory neurons of dorsal root, trigeminal, and nodose ganglia. AQP1 immunoreactivity is abundant in DRG cell bodies and in both the peripheral and central branches of primary afferent neurons, and colocalizes with markers of nociceptors, notably substance P and IB4. AQP1 expression in DRG is first detectable at embryonic day 15.5, which corresponds to the developmental stage when the majority of fine cutaneous afferents penetrate the dorsal horn. Electron microscopy revealed dense membrane labeling of unmyelinated axons, a few fine diameter myelinated axons, and synaptic terminals in the superficial dorsal horn. Because this restricted and dense expression suggested that AQP1 contributes to nociceptive processing, we studied behavioral responses of wildtype and AQP1 -/- mice in a comprehensive battery of acute and persistent pain tests. We also used in vivo electrophysiology in wildtype and mutant mice to measure the responses of wide dynamic range neurons in lamina V of the dorsal horn to thermal stimulation before and after noxious stimulus-induced sensitization. To date we have not detected a differential phenotype suggestive of a functional contribution of AQP1 to nociceptive processing.
Pain 2007 Sep
PMID:Anatomical and functional analysis of aquaporin 1, a water channel in primary afferent neurons. 1725 50

Aquaporins (AQPs) are small membrane channel proteins involved in osmoregulation. To date, only AQP1, AQP2, AQP4 and AQP9 have been found in the nervous system. Generally, they are involved in water movement in nervous tissue, nevertheless, recent data would suggest the involvement of AQPs in neurotransmission. In this work, we have evaluated the expression of AQP1 and AQP2 in the trigeminal ganglia of mice in an animal model of perioral acute inflammatory pain using immunohistochemistry and immunoblotting analysis. Our data have shown for the first time, the alteration of AQP2 expression in trigeminal ganglia in acute inflammatory pain showing increased and intracellular redistribution of AQP2 mainly in small-sized neurons and Schwann cells. Apart from this, the AQP1 expression remained unaltered. On the whole, these data support the hypothesis that AQP2 is involved in pain transmission in the peripheral nervous system.
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PMID:Alterations of AQP2 expression in trigeminal ganglia in a murine inflammation model. 1901 99

Although malfunction of spinal cord water channels (aquaporins, AQP) likely contributes to severe disturbances in ion/water homeostasis after spinal cord injury (SCI), their roles are still poorly understood. Here we report and discuss the potential significance of changes in the AQP4 expression in human SCI that generates glial fibrillary acidic protein (GFAP)-labeled astrocytes devoid of AQP4, and GFAP-labeled astroglia that overexpress AQP4. We used a rat model of contusion SCI to study observed changes in human SCI. AQP4-negative astrocytes are likely generated during the process of SCI-induced replacement of lost astrocytes, but their origin and role in SCI remains to be investigated. We found that AQP4-overexpression is likely triggered by hypoxia. Our transcriptional profiling of injured rat cords suggests that elevated AQP4-mediated water influx accompanies increased uptake of chloride and potassium ions which represents a protective astrocytic reaction to hypoxia. However, unbalanced water intake also results in astrocytic swelling that can contribute to motor impairment, but likely only in milder injuries. In severe rat SCI, a low abundance of AQP4-overexpressing astrocytes was found during the motor recovery phase. Our results suggest that severe rat contusion SCI is a better model to analyze AQP4 functions after SCI. We found that AQP4 increases in the chronic post-injury phase are associated with the development of pain-like behavior in SCI rats, while possible mechanisms underlying pain development may involve astrocytic swelling-induced glutamate release. In contrast, the formation and size of fluid-filled cavities occurring later after SCI does not appear to be affected by the extent of increased AQP4 levels. Therefore, the effect of therapeutic interventions targeting AQP4 will depend not only on the time interval after SCI or animal models, but also on the balance between protective role of increased AQP4 in hypoxia and deleterious effects of ongoing astrocytic swelling.
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PMID:Aquaporins in spinal cord injury: the janus face of aquaporin 4. 2010 36

Recent data suggest a possible involvement of Aquaporins (AQPs) in pain transmission. AQPs are small membrane channel proteins involved in osmoregulation and, to date, AQP1, AQP2, AQP3, AQP4, AQP5, AQP8 and AQP9 have been found in the nervous system. Nevertheless only AQP1, AQP2 and AQP4 seem to be involved in nociception.In this review, direct and indirect evidences of the role of AQPs in pain processing will be reported.
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PMID:Aquaporins in sensory and pain transmission. 2111 83

The expression and role of the aquaporin (AQP) family water channels in the peripheral nervous system was less investigated. Since 2004, however, significant progress has been made in the immunolocalization, regulation and function of AQPs in the peripheral nervous system. These studies showed selective localization of three AQPs (AQP1, AQP2, and AQP4) in dorsal root ganglion neurons, enteric neurons and glial cells, periodontal Ruffini endings, trigeminal ganglion neurons and vomeronasal sensory neurons. Functional characterization in transgenic knockout mouse model revealed important role of AQP1 in pain perception. This review will summarize the progress in this field and discuss possible involvement of AQPs in peripheral neuropathies and their potential as novel drug targets.
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PMID:Expression and function of aquaporins in peripheral nervous system. 2160 41

The expression and function of aquaporins (AQPs) in the peripheral nervous system is a relatively under-investigated subject. Since the original description of AQP1 mRNA expression in the trigeminal ganglion in 2004, there has been significant progress in describing the expression, regulation and function of AQPs in the peripheral nervous system. Three out of the 13 mammalian AQPs (AQP1, AQP2 and AQP4) have been localized to neurons or glial cells in trigeminal ganglia, periodontal Ruffini endings, dorsal root ganglia and the enteric nervous system. Functional studies using knockout mice have suggested the involvement of AQP1 in peripheral pain perception. This review discusses current progress in this field and the possible involvement of AQPs in peripheral neuropathies.
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PMID:Water channel proteins in the peripheral nervous system in health and disease. 2247 45

The aim of this article is to describe the roles of water channel proteins (WCPs) in brain functionality. The fluid compartments of the brain, which include the brain parenchyma (with intracellular and extracellular spaces), the intravascular and the cerebrospinal fluid compartments are presented. Then the localization and functional roles of WCPs found in the brain are described: AQP1, AQP2, AQP3, AQP4, AQP5, AQP7, AQP8, AQP9 and AQP11. In subsequent chapters the involvement of brain WCPs in pathologies are discussed: brain edema, brain trauma, brain tumors, stroke, dementia (Alzheimer's disease, human immunodeficiency virus--HIV-dementia), autism, pain signal transduction and migraine, hydrocephalus and other pathologies with neurological implications: eclampsia, uremia. New WCP ligands for brain imaging are also discussed.
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PMID:Brain water channel proteins in health and disease. 2250 60

The aquaporins (AQPs) are plasma membrane water-transporting proteins. AQP4 is the principal member of this protein family in the CNS, where it is expressed in astrocytes and is involved in water movement, cell migration and neuroexcitation. AQP1 is expressed in the choroid plexus, where it facilitates cerebrospinal fluid secretion, and in dorsal root ganglion neurons, where it tunes pain perception. The AQPs are potential drug targets for several neurological conditions. Astrocytoma cells strongly express AQP4, which may facilitate their infiltration into the brain, and the neuroinflammatory disease neuromyelitis optica is caused by AQP4-specific autoantibodies that produce complement-mediated astrocytic damage.
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PMID:Aquaporin water channels in the nervous system. 2348 83

Optic neuritis (ON) was rarely reported in juvenile idiopathic arthritis (JIA) patients, particularly in those under anti-tumor necrosis factor alpha blockage. However, to our knowledge, the prevalence of ON in JIA population has not been studied. Therefore, 5,793 patients were followed up at our University Hospital and 630 (11%) had JIA. One patient (0.15%) had ON and was reported herein. A 6-year-old male was diagnosed with extended oligoarticular JIA, and received naproxen and methotrexate subsequently replaced by leflunomide. At 11 years old, he was diagnosed with aseptic meningitis, followed by a partial motor seizure with secondary generalization. Brain magnetic resonance imaging (MRI) and electroencephalogram showed diffuse disorganization of the brain electric activity and leflunomide was suspended. Seven days later, the patient presented acute ocular pain, loss of acuity for color, blurred vision, photophobia, redness and short progressive visual loss in the right eye. A fundoscopic exam detected unilateral papilledema without retinal exudates. Orbital MRI suggested right ON. The anti-aquaporin 4 (anti-AQP4) antibody was negative. Pulse therapy with methylprednisolone was administered for five days, and subsequently with prednisone, he had clinical and laboratory improvement. In conclusion, a low prevalence of ON was observed in our JIA population. The absence of anti-AQP4 antibody and the normal brain MRI do not exclude the possibility of demyelinating disease associated with chronic arthritis. Therefore, rigorous follow up is required.
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PMID:[Optic neuritis in juvenile idiopathic arthritis patient]. 2543 5


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