Afferent Mechanisms Research Articles

Physiological Regulation of Magnocellular Neurosecretory Cell Activity: Integration of Intrinsic, Local and Afferent Mechanisms

The hypothalamic supraoptic and paraventricular nuclei contain magnocellular neurosecretory cells (MNCs) that project to the posterior pituitary gland where they secrete either oxytocin or vasopressin (the antidiuretic hormone) into the circulation. Oxytocin is important for delivery at birth and is essential for milk ejection during suckling. Vasopressin primarily promotes water reabsorption in the kidney to maintain body fluid balance, but also increases vasoconstriction. The profile of oxytocin and vasopressin secretion is principally determined by the pattern of action potentials initiated at the cell bodies. Although it has long been known that the activity of MNCs depends upon afferent inputs that relay information on reproductive, osmotic and cardiovascular status, it has recently become clear that activity depends critically on local regulation by glial cells, as well as intrinsic regulation by the MNCs themselves. Here, we provide an overview of recent advances in our understanding of how intrinsic and local extrinsic mechanisms integrate with afferent inputs to generate appropriate physiological regulation of oxytocin and vasopressin MNC activity.

Afferent sensory mechanisms involved in jaw gape-related muscle activation in unilateral biting

In unilateral biting or chewing, the working/balancing-side ratio (W/B-ratio) of masseter activities is inversely proportional to the jaw gape which was interpreted as a neuromuscular strategy to protect occlusion. This suggests that jaw separation is afferently perceived, raising the question how this perception might work. In related studies, isometric biting was exerted on rubber pieces that slightly yielded similar to compressed food in chewing. We hypothesized that minor jaw movements associated with this yielding are necessary to elicit a jaw gape-related control of relative activation in isometric biting. Surface electromyograms of masseter muscles were recorded bilaterally in 20 males during (a) unilateral chewing, (b) isometric biting on rubber pieces inducing jaw gapes of 5, 3, 2, 1, and 0.5 mm, and (c) isometric biting with teeth embedded in rigid splints causing gapes of 5 and 1 mm. With rubber, the masseter W/B-ratio increased from 100 % (5 mm) to 166 % (1 mm) (p = 0.0003) whereas with the splint it increased just slightly to 112 % (p = 0.005). With 1 mm gape, W/B-ratios in splint biting were significantly smaller than in rubber biting or in chewing (p = 0.01). We conclude that minor jaw motion preceding peak force in unilateral biting is necessary to create afferent sensory information that could elicit jaw gape-related activation of masseter muscles. Demonstrating a condition under which jaw gape-related activation can lose its occlusion protecting effect, these findings might contribute to disclose the causes of craniomandibular disorders.

The circulatory and renal sympathoinhibitory effects of gastric leptin are altered by a high fat diet and obesity

Gastric leptin elicits its cardiovascular and splanchnic sympathoinhibitory responses via a vagal afferent mechanism, however the latter are blunted/abolished in animals fed a medium high fat diet (MHFD). In a diet-induced obesity model we sought to determine whether the renal sympathetic nerve discharge (RSND) and regional vasodilator responses to gastric leptin are also affected by diet and/or obesity. The diet induced obesity model was used in 2 separate studies. After 13 weeks on a MHFD the animals were classified as either obesity prone (OP) or obesity resistant (OR) depending on their weight gain. Control animals were fed a low fat diet for an equivalent period. Arterial pressure (AP) and heart rate (HR) were monitored in isoflurane-anaesthetised, artificially ventilated animals and RSND or regional vascular responses to leptin (15 μg/kg) administered close to the coeliac artery were evaluated. OP rats had higher baseline AP compared to control/OR rats (P<0.05). Close arterial leptin inhibited RSND in control animals but this response was abolished in OR and OP animals (P<0.01 for both). Leptin administration increased renal vascular conductance in control animals but this response was significantly attenuated only in OP animals (P<0.05). The vasodilator response in the superior mesenteric artery was not significantly different in any of the groups (P>0.05). Together these results suggest that, while the renal sympathoinhibitory responses to gastric leptin are affected by diet, the vasodilator responses to leptin in the renal vascular bed are only affected in OP animals. These changes may impact on cardiovascular homeostatic mechanisms in obesity.

Neurobehavioural activation during peripheral immunosuppression

Like other physiological responses, immune functions are the subject of behavioural conditioning. Conditioned immunosuppression can be induced by contingently pairing a novel taste with an injection of the immunosuppressant cyclosporine A (CsA) in an associative learning paradigm. This learned immunosuppression is centrally mediated by the insular cortex and the amygdala. However, the afferent mechanisms by which the brain detects CsA are not understood. In this study we analysed whether CsA is sensed via the chemosensitive vagus nerve or whether CsA directly acts on the brain. Our experiments revealed that a single peripheral administration of CsA increases neuronal activity in the insular cortex and the amygdala as evident from increased electric activity, c-Fos expression and amygdaloid noradrenaline release. However, this increased neuronal activity was not affected by prior vagal deafferentation but rather seems to partially be induced by direct action of CsA on cortico-amygdaloid structures and the chemosensitive brainstem regions area postrema and nucleus of the solitary tract. Together, these data indicate that CsA as an unconditioned stimulus may directly act on the brain by a still unknown transduction mechanism.

Neurosensory assessments of migraine

Headache medicine is primarily dependent on patients' subjective reports of pain, which are assessed at diagnosis and throughout the duration of treatment. There is a need for an objective, quantitative biological measurement of headache pain severity. In this study, quantitative sensory testing (QST) was conducted via multi-site vibrotactile stimulation in patients with migraine. The purpose was to investigate the sensitivity of the method and to determine if the metrics obtained from migraineurs could be differentiated from controls. Metrics reflecting sensory percepts of baseline measures of stimulus amplitude discrimination, temporal order judgment, and duration discrimination were significantly different. Additional measures previously demonstrated to be sensitive to alterations in centrally-mediated information processing features such as adaptation and synchronization were also significantly different from control values. In contrast, reaction times and vibrotactile detection thresholds of migraineurs failed to differentiate them from controls, indicating that the results are not due to peripheral neuropathy or some other primary afferent mechanism. The long-term objective of the study is to develop methods that can improve diagnosis and enable more accurate assessments of treatment efficacy in migraine.

27 AFFERENT AND EFFERENT MECHANISMS ASSOCIATED WITH NEUROMODULATION OF THE BLADDER MICTURITION REFLEX IN THE RAT

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Basic Research I1 Apr 201227 AFFERENT AND EFFERENT MECHANISMS ASSOCIATED WITH NEUROMODULATION OF THE BLADDER MICTURITION REFLEX IN THE RAT Xin Su, Angela M. Nickles, and Dwight E. Nelson Xin SuXin Su Minneapolis, MN More articles by this author , Angela M. NicklesAngela M. Nickles Minneapolis, MN More articles by this author , and Dwight E. NelsonDwight E. Nelson Minneapolis, MN More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.070AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Spinal nerve stimulation (SNS, 10Hz) suppresses bladder micturition reflex contraction (BRC), either eliminating BRC or reducing the contraction frequency in a current dependent manner. Here we evaluate whether this suppression may be associated with increased bladder capacity (e.g. through afferent functions) or suppression of detrusor contractions (efferent functions). METHODS In female rats (urethane, i.p. 1.2g/kg), a monopolar electrode was placed under L6 spinal nerves. A bladder cannula was placed via the urethra for saline infusion and intravesical pressure recording. Saline infusion induced BRC. If SNS completely abolished BRC, we determined whether additional infusion could overcome bladder inhibition. RESULTS SNS attenuated the frequency but not amplitude of BRC. Two x motor threshold (2*Tmot), 3*Tmot, 4*Tmot and 6*Tmot significantly (p<0.05, vs. control, n=23) decreased the frequency of BRC during stimulation to 65.56 ± 17% (n=9), 10.64 ± 8% (n=8), 6.25 ± 6% (n=7), and 0% of controls (n=7), respectively. High intensity SNS abolished BRC. Additional saline re-established the BRC with a similar frequency but lower amplitude despite the presence of electrical stimulation (Fig 1A). During this time SNS produced a significant inhibition of the amplitude but not frequency of BRC (n=5, p<0.05, Fig 1B/C). CONCLUSIONS Bladder inhibitory effects of SNS are a consequence of an increased bladder capacity since SNS attenuates the frequency but not amplitude of BRC and the ‘shutdown' of the BRC can be re-established by additional saline infusion. Consistent with this, we previously reported that SNS increases voiding threshold and inter-contraction interval but not voiding pressure (Su et al., IPPS, 2011). However since SNS suppresses the amplitude of the re-established BRC, SNS may also directly depress detrusor contractility. These data suggest that SNS neuromodulation may act through two distinct stimulation modes. Lower stimulation intensities appear to be mediated through the afferent limb of the neural circuit and increase the bladder capacity. Higher intensities may additionally act through efferent neural pathways and attenuate amplitude of detrusor contractions as well as by increasing bladder capacity. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e10-e11 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Xin Su Minneapolis, MN More articles by this author Angela M. Nickles Minneapolis, MN More articles by this author Dwight E. Nelson Minneapolis, MN More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

The afferent system and its role in lower urinary tract dysfunction

Lower urinary tract disorders such as overactive bladder syndrome (OABS) and interstitial cystitis/painful bladder syndrome (IC/PBS) are debilitating conditions with serious adverse effects on quality of life. Common to both OABS and IC/PBS are the sensory symptoms of urgency and frequency, implicating the afferent system in the aetiology of these disorders. Thus, understanding the role that afferent pathways play in the function of the lower urinary tract is the focus of much current research. This review aims to provide an insight into the recent advances in this field. Sensory transduction in the bladder is not only mediated by direct activation of the afferents via a host of receptors and ion channels located on the afferent terminal but also may be attributed to the interplay between the urothelium and the release of urothelially derived mediators. Recent studies provide compelling evidence to support this concept and highlight the complex nature of the bladder afferent system. Recent studies provide further evidence that afferent control of the bladder may be dependent on integration of excitatory and inhibitory mediators from the urothelium such as ATP and nitric oxide. A number of studies have examined the role cholinergic and adrenergic mechanisms play in bladder afferent function, and several new potential mechanisms involving the cannabinoid receptors and transient receptor potential channels have emerged as areas which warrant further investigation. A better understanding of afferent mechanisms in the bladder will hopefully lead to more effective treatments of lower urinary tract disorders.

Researching bladder afferents—determining the effects of β3‐adrenergic receptor agonists and botulinum toxin type‐A

A substantial portion of the current research on lower urinary tract dysfunction is focused on afferent mechanisms. The main goals are to define and modulate the signaling pathways by which afferent information is generated, enhanced and conveyed to the central nervous system. Alterations in bladder afferent mechanisms are a potential source of voiding dysfunction and an emerging source for drug targets. Established drug therapies such as muscarinic receptor antagonists, and two emerging therapies, β(3) -adrenergic receptor agonists and botulinum toxin type-A, may act partly through afferent mechanisms. This review focuses on these two new principles and new and established methods for determining their sites of action. It also provides brief information on the innervation of the bladder, afferent receptors and transmitters and how these may communicate with the urothelium, interstitial cells and detrusor smooth muscle to regulate micturition. Peripheral and central mechanisms of afferent sensitization and myogenic mechanisms that lead to detrusor overactivity, overactive bladder symptoms and urgency sensations are also covered. This work is the result from 'Think Tank' presentations, and the lengthy discussions that followed, at the 2010 International Consultation on Incontinence Research Society meeting in Bristol, UK.

Simultaneous parasympathetic and sympathetic activation reveals altered autonomic control of heart rate, vascular tension, and epinephrine release in anesthetized hypertensive rats

Sympathetic hyperactivity and parasympathetic insufficiency characterize blood pressure (BP) control in genetic hypertension. This shift is difficult to investigate in anesthetized rats. Here we present a pharmacological approach to simultaneously provoke sympathetic and parasympathetic transmitter release, and identify their respective roles in the concomitant cardiovascular response. To stimulate transmitter release in anesthetized normotensive (WKY) and spontaneously hypertensive rats (SHR), we injected intravenously 4-aminopyridine (4-AP), a voltage-sensitive K+ channel (KV) inhibitor. A femoral artery catheter monitored BP, an ascending aorta flow-probe recorded cardiac output and heart rate (HR). Total peripheral vascular resistance (TPVR) was calculated. 4-AP-induced an immediate, atropine (muscarinic antagonist)- and hexamethonium (ganglion blocker)-sensitive bradycardia in WKY, and in both strains, a subsequent, sustained tachycardia, and norepinephrine but not epinephrine release. Reserpine (sympatholytic), nadolol (β-adrenoceptor antagonist) or right vagal nerve stimulation eliminated the late tachycardia, adrenalectomy, scopolamine (central muscarinic antagonist) or hexamethonium did not. 4-AP increased TPVR, transiently in WKY but sustained in SHR. Yohimbine (α2-adrenoceptor antagonist) prevented the TPVR down-regulation in WKY. Reserpine and prazosin (α1-adrenoceptor antagonist) eliminated the late vasoconstriction in SHR. Plasma epinephrine overflow increased in nadolol-treated SHR. Through inhibition of KV, 4-AP activated parasympathetic ganglion transmission and peripheral, neuronal norepinephrine release. The sympathetic component dominated the 4-AP–HR-response in SHR. α2-adrenoceptor-dependent vasodilatation opposed norepinephrine-induced α1-adrenergic vasoconstriction in WKY, but not SHR. A βAR-activated, probably vagal afferent mechanism, hampered epinephrine secretion in SHR. Thus, 4-AP activated the autonomic system and exposed mechanisms relevant to hypertensive disease.

Cannabinor, a Selective Cannabinoid-2 Receptor Agonist, Improves Bladder Emptying in Rats With Partial Urethral Obstruction

We studied the effects of chronic treatment with the novel selective cannabinoid 2 receptor agonist cannabinor (Procter & Gamble Pharmaceuticals, Cincinnati, Ohio) on bladder function in conscious rats with partial urethral obstruction and on the functional properties of isolated detrusor muscle. A total of 24 female Sprague-Dawley® rats with surgically created partial urethral obstruction received daily intraperitoneal injections of 3 mg/kg cannabinor (12) or saline as controls (12) for 2 weeks. Cystometry was done, the rats were sacrificed and the bladders were prepared for in vitro studies. Mean ± SEM bladder weight was 0.97 ± 0.15 gm in controls and 0.53 ± 0.08 gm in cannabinor treated rats (p <0.05). There was no difference between the groups in the mean micturition interval, or mean baseline, threshold, flow or maximum pressure. In controls and cannabinor treated rats mean post-void residual volume was 0.28 ± 0.07 and 0.06 ± 0.02 ml, mean micturition compliance was 0.032 ± 0.006 and 0.069 ± 0.016 ml/cm H(2)O, and mean bladder wall force at the start of flow was 950 ± 280 and 1,647 ± 325 mN/gm, respectively (each p <0.05). Nonvoiding contractions were significantly less frequent in cannabinor treated rats than in controls. We noted no difference in carbachol (Sigma®) half maximum concentration between the groups but the carbachol maximum response in detrusor strips from cannabinor treated rats was significantly higher than that in control strips. In rats with partial urethral obstruction treated daily for 14 days with cannabinor bladder weight was lower, the ability to empty the bladder was preserved and nonvoiding contraction frequency was low compared to those in controls. Detrusor preparations from cannabinor treated rats showed a higher response to nerve stimulation than those from controls. Selective cannabinoid 2 receptor activation may be a novel principle to enable improved bladder function after partial urethral obstruction.

VGLUT2 expression in primary afferent neurons is essential for normal acute pain and injury-induced heat hypersensitivity

Dorsal root ganglia (DRG) neurons, including the nociceptors that detect painful thermal, mechanical, and chemical stimuli, transmit information to spinal cord neurons via glutamatergic and peptidergic neurotransmitters. However, the specific contribution of glutamate to pain generated by distinct sensory modalities or injuries is not known. Here we generated mice in which the vesicular glutamate transporter 2 (VGLUT2) is ablated selectively from DRG neurons. We report that conditional knockout (cKO) of the Slc17a6 gene encoding VGLUT2 from the great majority of nociceptors profoundly decreased VGLUT2 mRNA and protein in these neurons, and reduced firing of lamina I spinal cord neurons in response to noxious heat and mechanical stimulation. In behavioral assays, cKO mice showed decreased responsiveness to acute noxious heat, mechanical, and chemical (capsaicin) stimuli, but responded normally to cold stimulation and in the formalin test. Strikingly, although tissue injury-induced heat hyperalgesia was lost in the cKO mice, mechanical hypersensitivity developed normally. In a model of nerve injury-induced neuropathic pain, the magnitude of heat hypersensitivity was diminished in cKO mice, but both the mechanical allodynia and the microgliosis generated by nerve injury were intact. These findings suggest that VGLUT2 expression in nociceptors is essential for normal perception of acute pain and heat hyperalgesia, and that heat and mechanical hypersensitivity induced by peripheral injury rely on distinct (VGLUT2 dependent and VGLUT2 independent, respectively) primary afferent mechanisms and pathways.

Evidence based integrative medicine

Integrative approaches have played an essential role in the treatment of dermatological diseases since a long time. Many current standard treatments can be considered integrative such as phototherapy, climate therapy (such as staying at high altitude or at the sea), special training on how to handle a disease, special diets and psychological approaches. Furthermore the amount of well-controlled studies on complementary medicine in the treatment of dermatological disorders has increased within the last years. Besides different therapies derive from natural remedies, such as fumaric acid or psoralene (used e.g. in the treatment of psoriasis). An example reflecting the integrative approach in dermatology is the treatment of atopic eczema—an inflammatory, chronically relapsing, non-contagious and pruritic skin disease. Amongst others it consists in rehydration, anti-inflammation, antisepsis, avoidance of trigger factors and anti-pruritic strategies. The large number of emollients currently used includes many naturally derived topical agents. Anti-inflammatory standard treatment with corticosteroids and calcineurin-inhibitors is complemented by e.g. phototherapy or topical usage of e.g. soaked black tea pads as further treatment options. In case of antimicrobial treatment a variety of natural agents such as tea tree oil, lemongrass and cinnamon oil proved a strong anti-bacterial effect. Due to their potency to induce contact allergies they are, however, not recommended; neither are antibiotics. Non-irritating antiseptics are the agents of choice. Avoidance of triggering factors includes amongst others staying at high altitude or at the sea as well as special diets and avoidance of allergens. Antipruritic treatment includes topical therapies with anesthetics and corticosteroids as well as cold showers. Within the last years some promising new approaches have evolved, which have to further be evaluated regarding its clinical effect on atopic eczema: Recent experimental studies have e.g. shown an effect of acupuncture on histamine- and allergen-induced itch and an influence of allergen-induced basophil activation. Sangre de grado, an Amazonian medicinal, showed to be a potent antimicrobial, anti-inflammatory and inhibitor of sensory afferent nerve mechanisms. Future studies will have to further focus on the role of integrative medicine in dermatology.

Dyspnoe-Algorithmen für Praxis und Notfallstation

The evaluation of dyspnea in the Emergency Department (ED) is a critical step in the diagnostic procedure, especially when cardiopulmonary disease is suspected. Because dyspnea is a symptom in which many different afferent mechanisms are involved, a large number of underlying causes must be considered, alone or in combination. Qualitative and quantitative aspects of difficult or laboured breathing may vary extremely between patients. Therefore, especially under time pressure in emergency situations, it is important to consider a very broad differential diagnosis, and at the same time use a standardized protocol or diagnostic algorithms for the initial work-up.In this article, a standardized work-up published by family practitioners is compared to a standardized work-up proposed by our ED. While practitioners may safely use a multi-step algorithmic approach, it is important in the ED to consider all possible serious underlying conditions at the same time. Over 90 % of all emergency situations are accounted for by only 7 different disease groups. Therefore, all of these must be considered simultaneously in a protocol that is useful for emergency physicians.

The evolving physiology of the lower urinary tract: What we are learning and where we need to go

Much of the current research on the physiology of the lower urinary tract is focused on afferent mechanisms, and we are learning how to control two of the identified signaling pathways by which afferent information is generated and conveyed to the central nervous system: the myogenic and urothelial (mucosal) pathways. The myogenic pathway is activated via “in series” mechanoreceptors responding to distention and via spontaneous contractile activity in units of myocytes generating “afferent noise.” The mucosal pathway is a functional unit consisting of the urothelium itself, suburothelial interstitial cells, and afferent nerves that signal via muscle-mucosal mechanoreceptors, mucosal mechanoreceptors, and chemoreceptors. To control micturition when it is dysfunctional, we need to know more about all the components involved in normal micturition regulation. These include central control mechanisms. More information is needed to understand brain control of bladder function and to develop centrally acting agents to control bladder activity.

Botulinum toxin: future developments

The proposed mechanisms of action of botulinum neurotoxin-A (BoNT-A) in the bladder provide new insights that might help to understand better the complex machinery of the bladder wall and the importance of the afferent signalling mechanisms. BoNT-A might thus become to be considered a small revolution in the understanding and treatment of bladder overactivity. However, substantially more clinical and basic scientific data are needed before we can truly claim to comprehend how it influences lower urinary tract function, or its role in managing urological problems.

Fast Locomotor Burst Generation in Late Stage Embryonic Motility

We examined muscle burst patterns and burst frequencies for a distinct form of repetitive leg movement recently identified in chick embryos at embryonic day (E)18 that had not been previously studied. The aim was to determine if burst frequencies during repetitive leg movements were indicative of a rhythm burst generator and if maturing muscle afferent mechanisms could modulate the rhythm. Electromyographic recordings synchronized with video were performed in ovo during spontaneous movement at E15, E18, and E20. Multiple leg muscles were rhythmically active during repetitive leg movements at E18 and E20. Rhythmic activity was present at E15 but less well formed. The ankle dorsi flexor, tibialis anterior, was the most reliably rhythmic muscle because extensor muscles frequently dropped out. Tibialis anterior burst frequencies ranged from 1 to 12 Hz, similar to frequencies during fast locomotor burst generation in lamprey. The distribution in burst frequencies at E18 was greatest at lower frequencies and similar to locomotor data in hatchlings. Relative distributions were more variable at E20 and shifted toward faster frequencies. The shell wall anterior to the leg was removed in some experiments to determine if environmental constraints associated with growth contributed to frequency distributions. Wall removal had minimal impact at E18. E20 embryos extended their foot outside the egg, during which faster frequencies were observed. Our findings provide evidence that embryonic motility in chick may be controlled by a fast locomotor burst generator by E15 and that modulation by proprioceptors may emerge between E18 and E20.

Physiologic and Pathophysiologic Functions of Purinoceptors in Voiding Reflex

Purinergic neurotransmission has been regarded as major component of non-adrenergic, noncholinergic (NANC) contraction in detrusor smooth muscle. Although in normal human detrusor, this contraction seems to be small, the importance of the NANC component for detrusor contraction in disease conditions such as detrusor overactivity remains to be established. Based on many evidences for purinergic contributions in lower urinary tract, ATP and purinoceptors has been suggested to be involved in both efferent and afferent mechanism in voiding reflex. ATP signaling via P2X1 receptors plays an important role in efferent neural control of urinary bladder function, although to varying degrees across species from experimental animals to men. The efferent function of purinoceptors may be enhanced in detrusor overactivity and aging. ATP also suggested being involved in mechanosensory transmission, via activation of P2X3 and P2X2/3 receptors on sensory afferent nerves. The afferent function of purinoceptors may be related with pathophysiology of overactive bladder or interstitial cystitis, mediating bladder hyperexicitability. These results suggest that the selective antagonists for the purinoceptors may offer better relief of sensory and motor symptoms for overactive bladder or interstitial cystitis patients in the future. (J Korean Continence Soc 2008;12:93-8)

On the origin of bladder sensing: Tr(i)ps in urology

The mammalian TRP family consists of 28 channels that can be subdivided into 6 different classes: TRPV (vanilloid), TRPC (canonical), TRPM (Melastatin), TRPP (Polycystin), TRPML (Mucolipin), and TRPA (Ankyrin). TRP channels are activated by a diversity of physical (voltage, heat, cold, mechanical stress) or chemical (pH, osmolality) stimuli and by binding of specific ligands, enabling them to act as multifunctional sensors at the cellular level. Currently, a lot of scientific research is devoted to these channels and their role in sensing mechanisms throughout the body. In urology, there's a growing conviction that disturbances in afferent (sensory) mechanisms are highly important in the pathogenesis of functional problems. Therefore, the TRP family forms an interesting new target to focus on. In this review we attempt to summarize the existing knowledge about TRP channels in the urogenital tract. So far, TRPV1, TRPV2, TRPV4, TRPM8, and TRPA1 have been described in different parts of the urogenital tract. Although only TRPV1 (the vanilloid receptor) has been extensively studied so far, more evidence is slowly accumulating about the role of other TRP channels in the (patho)physiology of the urogenital tract.

Electroacupuncture treatment of arrhythmias in myocardial ischemia

integrative medicine, sometimes also called complementary and alternative medicine (or CAM), has been classified by the National Center for Complementary and Alternative Medicine into five domains, including 1 ) alternative systems of medical practice, like traditional Chinese medicine; 2 ) mind-

Urothelial and Afferent Mechanisms Inducing Bladder Pain in Interstitial Cystitis

Although the symptoms of interstitial cystitis (IC)–a debilitating, chronic disease characterized by urinary urgency and frequency, and bladder and pelvic pain on bladder filling–are easily confused with those of urinary tract infections, there is an absence of an underlying infection, and antibiotic therapy is of no therapeutic benefit. Severe cases of this disorder, which affects primarily women, can have considerable impact on the quality of life of patients due to extreme pain and urinary frequency, which are often difficult to treat. Although the etiology of IC is still not known, several potential pathogeneses including epithelial dysfunction, increased urothelial-afferent interaction, neurogenic inflammation and hyperexcitability of bladder afferent pathways have been proposed. As knowledge of the pathogenesis of IC increases through intensified research, the ability to provide effective treatments to patients with this disease will improve.