Intramuscular Neurotrophin-3 normalizes low threshold spinal reflexes, reduces spasms and improves mobility after bilateral corticospinal tract injury in rats.

Brain and spinal injury reduce mobility and often impair sensorimotor processing in the spinal cord leading to spasticity. Here, we establish that complete transection of corticospinal pathways in the pyramids impairs locomotion and leads to increased spasms and excessive mono- and polysynaptic low threshold spinal reflexes in rats. Treatment of affected forelimb muscles with an adeno-associated viral vector (AAV) encoding human Neurotrophin-3 at a clinically-feasible time-point after injury reduced spasticity. Neurotrophin-3 normalized the short latency Hoffmann reflex to a treated hand muscle as well as low threshold polysynaptic spinal reflexes involving afferents from other treated muscles. Neurotrophin-3 also enhanced locomotor recovery. Furthermore, the balance of inhibitory and excitatory boutons in the spinal cord and the level of an ion co-transporter in motor neuron membranes required for normal reflexes were normalized. Our findings pave the way for Neurotrophin-3 as a therapy that treats the underlying causes of spasticity and not only its symptoms.

[Accidental mercury poisoning in a 12-year-old girl]. / Intoxication accidentelle au mercure chez l'enfant.

INTRODUCTION: Exposure to metallic mercury can cause severe accidental intoxications in children, whose clinical symptoms can vary depending on the route of administration, the dose, as well as the time and duration of the exposure. It has become unusual in France, yet it must be considered when taking a patient's medical history in cases of multisystemic involvement without a clear explanation. CLINICAL CASE: We report the case of a 12-year-old patient hospitalized because of a cough, poor general condition, chills, night sweats, psychomotor retardation, and skin lesions that had been developing for several weeks. The initial clinical examination also revealed sinus tachycardia, arterial hypertension, and abolition of osteotendinous reflexes. Complementary examination results were normal apart from a glomerular proteinuria without renal failure. When interviewing the mother, she reported that the child had played with mercury balls 3 months earlier. The suspicion of poisoning was confirmed by blood and urine analysis as well as renal biopsy showing an aspect of membranous glomerulonephritis with IgG and C3 depositions. An intoxication via a transdermal route being unlikely on healthy skin, the Regional Health Agency's survey concluded that chronic intoxication had occurred by inhalation of the mercury spread on the floor at the time of the exposure, which was then vacuum cleaned and released again by the contaminated vacuum cleaner. The patient's outcome was favorable within a few weeks after initiating DMSA chelation therapy. CONCLUSION: Mercury poisoning should be considered in cases of a multisystemic disorder without clear explanation, in order to intervene quickly and thus prevent irreversible renal and neurological consequences.

Role played by interleukin-6 in evoking the exercise pressor reflex in decerebrate rats: effect of femoral artery ligation.

IL-6 signaling via the soluble IL-6 receptor (sIL-6r) has been shown to increase primary afferent responsiveness to noxious stimuli. This finding prompted us to test the hypothesis that IL-6 and sIL-6r would increase the exercise pressor reflex in decerebrate rats with freely perfused femoral arteries. We also tested the hypothesis that soluble glycoprotein (sgp)130, an inhibitor of IL-6/sIL-6r signaling, would decrease the exaggerated exercise pressor reflex that is found in decerebrate rats with ligated femoral arteries. In rats with freely perfused femoral arteries, coinjection of 50 ng of IL-6 and sIL-6r into the arterial supply of the hindlimb significantly increased the peak pressor response to static (control: 14 ± 3 mmHg and IL-6/sIL-6r: 17 ± 2 mmHg, P = 0.03) and intermittent isometric (control: 10 ± 2 mmHg and IL-6/sIL-6r: 15 ± 4 mmHg, P = 0.03) hindlimb muscle contraction. In rats with ligated femoral arteries, injection of 50 ng of sgp130 into the arterial supply of the hindlimb reduced the peak pressor response to static (control: 24 ± 2 mmHg and sgp130: 16 ± 3 mmHg, P = 0.01) and intermittent isometric (control: 16 ± 2 mmHg and sgp130: 13 ± 2 mmHg, P = 0.04) hindlimb muscle contraction, whereas there was no effect of sgp130 on the exercise pressor reflex in rats with freely perfused femoral arteries. We conclude that coinjection of exogenous IL-6 and sIL-6r increased the exercise pressor reflex in rats with freely perfused femoral arteries. More importantly, we also conclude that IL-6 and sIL-6r play an endogenous role in evoking the exercise pressor reflex in rats with ligated femoral arteries but not in rats with freely perfused femoral arteries.

Effect of intravesical botulinum neurotoxin-A injection on detrusor hyperreflexia in spinal cord injured patients.

PURPOSE: To evaluate the effects of Botulinum Toxin A injection into the detrusor muscle on various voiding parameters in spinal cord injured patients with neurogenic detrusor hyperreflexia Materials and methods: 24 patients with spinal cord injuries who had detrusor overactivity and urinary incontinence and were refractory to oral medications, were injected 300 IU of BTX-A into the detrusor muscle. The pre-and post-treatment evaluations included determination of bladder urinary continence status, frequency/volume chart of CIC, Incontinence Quality of Life questionnaire (I-QOL) and patient satisfaction. The urodynamic parameters measured included maximum cystometric capacity (MCC), reflex detrusor volume (RDV) and maximum detrusor pressure during bladder contraction (MDP) were analyzed at the outset and during the follow-up (2, 6, and 24 weeks) examinations. RESULTS: The evaluation of urodynamic parameters during follow-up examinations (2, 6 and 24 weeks) revealed significant increase in mean reflex volume (p<0.05) and cystometric capacity (p<0.05), on the other detrusor pressure decreased significantly (p<0.05). In majority of patients there was considerable reduction in incontinence episodes and no complications or side effects were reported. Most of the patents were satisfied with the treatment. CONCLUSION: The use of Botulinum toxin type A for treatment of neurogenic detrusor overactivity in spinal cord injured patients is safe and efficacious. In our 24-week study period, there was significant improvement in most urodynamic parameters with consistence and subjective satisfaction indicated by the treated patients.

[Spasm of the near reflex. Treatment with botulinum toxin]. / Espasmo del reflejo de cerca. Tratamiento con toxina botulínica.

CLINICAL CASE: A 38-year old female with diplopia and esotropia, with limitation of ocular abduction in both eyes, with full abduction after doll's head rotation also being observed. She was diagnosed with spasm of the near reflex. Treatment with injections of botulinum toxin in both medial rectus has temporally resolved the convergence spasm. DISCUSSION: Near reflex spasm is characterized as miosis, pseudomyopia, and convergent strabismus that lead to diplopia, blurred vision, headache, and variable, progressive, and intermittent esotropia. As the spasm worsens there will be limited ocular versions and ductions simulating a sixth nerve palsy. Botulinum toxin may be effective in some cases.

[Neurological examination in patients undergoing sedation with propofol: a descriptive study]. / Exploracion neurologica en pacientes sometidos a sedacion con propofol: estudio descriptivo.

INTRODUCTION: The neurological examination is a resource used in evaluating patients who are in coma. Anaesthesia can be a factor that exerts an influence on the findings. We evaluated the examination of the comatose patient in the case of patients anaesthetised with propofol in order to define its clinical value. PATIENTS AND METHODS: A prospective study was conducted among those who had undergone heart surgery in the intensive care unit of a tertiary hospital during the months of April and May 2011. Aspects that were analysed were the examination of the anaesthetic coma, pharmacological or medical factors that can have an influence and a full neurological examination following recovery. Patients with previous neurological symptoms were excluded. RESULTS: Thirty patients were selected (16 males and 14 females); mean age: 72 ± 10 years. All the patients were sedated with propofol. During sedation, 17 (46.7%) presented unreactive pupils. No spontaneous eye movements were observed in 100% of the sample. Ocular alterations in primary position were observed in 23.3% of them. Oculocephalic reflexes were absent in 93.3% and oculovestibular reflexes, in 100%; the corneal reflex, was absent in 70% (with asymmetry), as was the ciliospinal reflex, in 83.3%. The algesic motor response was absent in 93.3%, as were the cutaneous plantar extensor reflexes, in 20%; and 66.7% were indifferent. Following anaesthesia, the neurological examination was normal in 80%, there were slight orientation impairments in 16.7% and a hemispheric syndrome was found in one patient. CONCLUSIONS: Anaesthesia with propofol alters the reversible cutaneous-plantar, pupillary, trunk and motor response reflexes on withdrawing sedation. The alterations may be asymmetrical. Neurological examinations should not be used in the case of patients sedated with propofol in order to make clinical decisions.

TITLE: Exploracion neurologica en pacientes sometidos a sedacion con propofol: estudio descriptivo.Introduccion. La exploracion neurologica es un recurso en la evaluacion de los pacientes en coma. La anestesia puede ser un factor influyente en los hallazgos. Evaluamos la exploracion del paciente en coma en pacientes anestesiados con propofol para definir su valor clinico. Pacientes y metodos. Estudio prospectivo en sometidos a cirugia cardiaca en los cuidados intensivos de un hospital terciario durante los meses de abril y mayo de 2011. Se analiza la exploracion del coma anestesico, factores farmacologicos o medicos que pueden influir y exploracion neurologica completa tras la recuperacion. Se excluyeron pacientes con sintomas neurologicos previos. Resultados. Se seleccionan 30 pacientes (16 hombres y 14 mujeres); edad media: 72 ± 10 años. Todos los pacientes estaban sedados con propofol. Durante la sedacion, 17 (46,7%) presentaban pupilas arreactivas. En el 100% no se observaron movimientos espontaneos de los ojos. El 23,3% presentaba alteracion ocular en posicion primaria. Los reflejos oculocefalicos estaban ausentes en el 93,3%, y los oculovestibulares, en el 100%; el reflejo corneal, en el 70% (con asimetria); el espinociliar, en el 83,3%. La respuesta motora algesica estaba ausente en el 93,3%; en un 20%, los reflejos cutaneoplantares extensores; e indiferentes, en el 66,7%. Tras la anestesia, la exploracion neurologica fue normal en el 80%, hubo leves alteraciones de orientacion en un 16,7% y se encontro un sindrome hemisferico en un paciente. Conclusiones. La anestesia con propofol altera los reflejos pupilares, del tronco, respuestas motoras y reflejo cutaneoplantar reversibles al retirar la sedacion. Las alteraciones pueden ser asimetricas. No se deberia utilizar la exploracion neurologica en el paciente sedado con propofol para la toma de decisiones clinicas.

Development of attenuated baroreflexes in obese Zucker rats coincides with impaired activation of nucleus tractus solitarius.

Adult obese Zucker rats (OZR; >12 wk) develop elevated sympathetic nerve activity (SNA) and mean arterial pressure (MAP) with impaired baroreflexes compared with adult lean Zucker rats (LZR) and juvenile OZR (6-7 wk). In adult OZR, baroreceptor afferent nerves respond normally to changes in MAP, whereas electrical stimulation of baroreceptor afferent fibers produces smaller reductions in SNA and MAP compared with LZR. We hypothesized that impaired baroreflexes in OZR are linked to reduced activation of brain stem sites that mediate baroreflexes. In conscious adult rats, a hydralazine (HDZ)-induced reduction in MAP evoked tachycardia that was initially blunted in OZR, but equivalent to LZR within 5 min. In agreement, HDZ-induced expression of c-Fos in the rostral ventrolateral medulla (RVLM) was comparable between groups. In contrast, phenylephrine (PE)-induced rise in MAP evoked markedly attenuated bradycardia with dramatically reduced c-Fos expression in the nucleus tractus solitarius (NTS) of adult OZR compared with LZR. However, in juvenile rats, PE-induced hypertension evoked comparable bradycardia in OZR and LZR with similar or augmented c-Fos expression in NTS of the OZR. In urethane-anesthetized rats, microinjections of glutamate into NTS evoked equivalent decreases in SNA, heart rate (HR), and MAP in juvenile OZR and LZR, but attenuated decreases in SNA and MAP in adult OZR. In contrast, microinjections of glutamate into the caudal ventrolateral medulla, a target of barosensitive NTS neurons, evoked comparable decreases in SNA, HR, and MAP in adult OZR and LZR. These data suggest that OZR develop impaired glutamatergic activation of the NTS, which likely contributes to attenuated baroreflexes in adult OZR.

Sudden asystole due to trigeminocardiac reflex during transsphenoidal surgery for pituitary tumor.

BACKGROUND: A sudden attack of an asystolic phenomenon is an extremely rare event during transsphenoidal surgery (TSS). It may be caused by an extreme type of trigeminocardiac reflex (TCR) during the manipulation of the trigeminal nerve or its innervated structures. CASE DESCRIPTION: We report two cases of sudden asystole and a case of severe bradycardia due to TCR during TSS. All patients were managed successfully by cessation of the surgical manipulation or with the injection of an anticholinergic agent. CONCLUSIONS: Although TCR occurs rarely and usually is self-limiting, surgeons should be cautious of its occurrence, especially when manipulating the cavernous sinus during TSS. This allows the early detection and appropriate treatment of this manifestation. Stopping the surgical procedure as soon as TCR occurs is likely to normalize the vital parameters. In addition, if further manipulations are inevitable, the administration of anticholinergic medication should be considered cautiously to improve surgical outcomes.

Toxic leukoencephalopathy due to transdermal fentanyl overdose.

Children with altered mental status who present to the emergency department have a broad differential diagnosis. We report a case of a 19-month-old girl who presented in coma and who was later found to have a fentanyl patch adhered to her back. She was found to have changes on brain magnetic resonance imaging consistent with a toxic spongiform leukoencephalopathy but had a good neurologic outcome. This case report illustrates the importance of a thorough physical examination in children in coma and a rarely reported magnetic resonance imaging finding that has been seen in opioid intoxication and is usually associated with severe morbidity and mortality.

Expression and function of CXCL12/CXCR4 in rat urinary bladder with cyclophosphamide-induced cystitis.

Chemokines, otherwise known as chemotactic cytokines, are proinflammatory mediators of the immune response and have been implicated in altered sensory processing, hyperalgesia, and central sensitization following tissue injury or inflammation. To address the role of CXCL12/CXCR4 signaling in normal micturition and inflammation-induced bladder hyperreflexia, bladder inflammation in adult female Wistar rats (175-250 g) was induced by injecting cyclophosphamide (CYP) intraperitoneally at acute (150 mg/kg; 4 h), intermediate (150 mg/kg; 48 h), and chronic (75 mg/kg; every 3rd day for 10 days) time points. CXCL12, and its receptor, CXCR4, were examined in the whole urinary bladder of control and CYP-treated rats using enzyme-linked immunosorbent assays (ELISAs), quantitative PCR (qRT-PCR), and immunostaining techniques. ELISAs, qRT-PCR, and immunostaining experiments revealed a significant (P < or = 0.01) increase in CXCL12 and CXCR4 expression in the whole urinary bladder, and particularly in the urothelium, with CYP treatment. The functional role of CXCL12/CXCR4 signaling in micturition was evaluated using conscious cystometry with continuous instillation of saline and CXCR4 receptor antagonist (AMD-3100; 5 microM) administration in control and CYP (48 h)-treated rats. Receptor blockade of CXCR4 using AMD-3100 increased bladder capacity in control (no CYP) rats and reduced CYP-induced bladder hyperexcitability as demonstrated by significant (P < or = 0.01) increases in intercontraction interval, bladder capacity, and void volume. These results suggest a role for CXCL12/CXCR4 signaling in both normal micturition and with bladder hyperreflexia following bladder inflammation.

Acute methotrexate neurotoxicity with choreiform movements and focal neurological deficits: a case report.

Methotrexate (MTX) is an effective antimetabolite treatment for various oncological disorders including the central nervous system involvement (CNS) in widespread leukemia and CNS lymphoma. This form of treatment has a notable toxic effect on the nervous system, and the pediatric population seems to be more vulnerable to the neurologic toxicity of this drug. Though chronic leukoencephalopathy from an MTX regimen, especially when administered in conjunction with whole brain radiation, is well described, the acute manifestations are rare and not well understood. The diagnosis of acute focal symptoms from MTX treatment is especially difficult in patients who receive chemotherapy for neoplastic disorders and who may have many reasons for CNS involvement in general and parenchymal involvement in particular. We report the unusual clinical and neuro-imaging findings in a teenager with acute focal symptoms after MTX treatment for acute lymphoblastic leukemia.

Trigemino-cardiac reflex in humans initiated by peripheral stimulation during neurosurgical skull-base operations. Its first description.

BACKGROUND: The trigemino-cardiac reflex (TCR) is a well-recognised phenomenon (first described in skull base surgery by the authors in 1999) that consists of bradycardia, arterial hypotension, apnoea, and gastric hypermobility. TCR occurs during skull base surgery at or around structures that are innervated by any sensory branch of the trigeminal nerve. Thus far, it has not been shown that peripheral stimulation of a trigeminal nerve can also cause this reflex. METHODS: The TCR was defined as clinical hypotension with a drop in mean arterial blood pressure (MABP) and in heart rate (HR) of more than 20% compared to the baseline level and coinciding with the surgical manipulation at or around any branches of the trigeminal nerve. The anaesthesiological and the operative techniques that were used were standardised. CLINICAL FEATURES: We describe here a 29-year-old woman with an endocrinological and imaging-proved micro-prolactinoma in which a TCR with a decrease in "arterial blood pressure" (130/70 mmHg up to a 100/40 mmHg) and an accompanying decrease of the HR (70 beats/min to 50 beats/min) was seen during preparation of the nasal mucosa for a transsphenoidal approach under general anaesthesia, lasting a few seconds until normalisation. After immediate application of atropine, the surgical procedure and the post-operative course was uneventful. MANAGEMENT: We present the first report of peripheral stimulation of a sensory branch of the trigeminal nerve that leads to a TCR under general anaesthesia according to our strict criteria as defined in 1999. The present finding is therefore a key research development and gives substantial evidence that TCR is coincident enhancement of sympathetic and parasympathetic outflows to the heart, suggesting that genetic differences may affect the susceptibility for TCR.

Thalamic microinjection of nicotine reverses sevoflurane-induced loss of righting reflex in the rat.

BACKGROUND: Neuronal nicotinic acetylcholine receptors are both potently inhibited by anesthetics and densely expressed in the thalamus. Brain imaging shows that thalamic activity suppression accompanies anesthetic-induced unconsciousness. Therefore, anesthetic-induced unconsciousness may involve direct antagonism of thalamic nicotinic receptors. The authors test this by separately attempting to block or enhance anesthetic-induced loss of righting in rats using intrathalamic microinjections of nicotine or its antagonist. METHODS: Rats were implanted with a cannula aimed at the thalamus or control locations. A week later, loss of righting was induced using sevoflurane (1.4 +/- 0.2%). A dose-parameter study (n = 35) first identified an optimal intrathalamic nicotine dose associated with arousal. Subsequently, this dose was used to pinpoint the thalamic site mediating the arousal response (n = 107). Finally, sevoflurane righting dose and response specificity were assessed after blocking nicotinic channels with intrathalamic mecamylamine pretreatment (n = 8) before nicotine challenge. RESULTS: Nicotine (150 microg/0.5 microl over 1 min) was the optimal arousal dose, because lower doses (75 microg) were ineffective and higher doses (300 microg) often caused seizures. Nicotine temporarily restored righting and mobility in animals when microinjections involved the central medial thalamus (P < 0.0001, chi-square). Righting occurred despite continued sevoflurane administration. Intrathalamic mecamylamine pretreatment did not lower the sevoflurane dose associated with loss of righting, but prevented the nicotine arousal response. CONCLUSIONS: The reversal of unconsciousness found here with intrathalamic microinfusion of nicotine suggests that suppression of the midline thalamic cholinergic arousal system is part of the mechanism by which anesthetics produce unconsciousness.

Characterization and restoration of altered inhibitory and excitatory control of micturition reflex in experimental autoimmune encephalomyelitis in rats.

Multiple sclerosis (MS) is characterized by inflammatory lesions throughout the central nervous system. Spinal cord inflammation correlates with many neurological defecits. Most MS patients suffer from micturition dysfunction with urinary incontinence and difficulty in emptying the bladder. In experimental autoimmune encephalomyelitis (EAE) induced in female Lewis rats, a model of MS, we investigated at distinct clinical severity scores the micturition reflex by cystometrograms. All rats presenting symptomatic EAE suffered from micturition reflex alterations with either detrusor areflexia or hyperactivity. During pre-symptomatic EAE, a majority of rats presented with detrusor areflexia, whereas at onset of clinical EAE, detrusor hyperactivity was predominant. During progression of EAE, detrusor areflexia and hyperactivity were equally expressed. Bladder hyperactivity was suppressed by activation of glycine and GABA receptors in the lumbosacral spinal cord with an order of potency: glycine > GABA(B) > GABA(A). Detrusor areflexia was transformed into detrusor hyperactivity by blocking glycine and GABA receptors. Spinalization abolished bladder activity in rats presenting detrusor hyperactivity and failed to induce activity in detrusor areflexia. Altogether, the results reveal an exaggerated descending excitatory control in both detrusor reflex alterations. In detrusor areflexia, a strong segmental inhibition dominates this excitatory control. As in treatment of MS, electrical stimulation of sacral roots reduced detrusor hyperactivity in EAE. Blockade of glycine receptors in the lumbosacral spinal cord suppressed the stimulation-induced inhibitory effect. Our data help to better understand bladder dysfunction and treatment mechanisms to suppress detrusor hyperactivity in MS.

Optimal end-tidal concentration of sevoflurane to test an ankle clonus in children.

STUDY DESIGN: A prospective randomized study on the end-tidal concentrations of sevoflurane at which ankle clonus existed. SUMMARY OF BACKGROUND DATA: The ankle clonus reflex is a transient neurologic abnormality, which normally occurs in patients during emergence from general anesthesia. OBJECTIVE: To determine the optimal end-tidal concentration of sevoflurane to test an ankle clonus in children during emergence from general anesthesia. METHODS: We studied 30 children (aged 5-15 years). General anesthesia was induced with thiopental sodium. Anesthesia was maintained with sevoflurane, oxygen, and air. At completion of surgery, 3% volume of the end-tidal sevoflurane concentration was maintained for at least 10 minutes. Ankle clonus was checked at 1.0% to 0.1% volume of the end-tidal sevoflurane concentration with an interval of 0.05% volume. RESULTS: Of children, 80% had bilateral ankle clonus, which was found most frequently when patients responded poorly to verbal commands. The median of the end-tidal sevoflurane concentration for a reactive ankle clonus was 0.45% volume (interquartile range 0.5% to 0.4% volume). CONCLUSIONS: The ankle clonus should be tested at 0.45% volume of end-tidal sevoflurane concentration in children undergoing scoliosis surgery during emergence from the general anesthesia.

A role for pituitary adenylate cyclase activating polypeptide (PACAP) in detrusor hyperreflexia after spinal cord injury (SCI).

Intrathecal administration of the PAC1 receptor antagonist, PACAP6-38 (10 nM), significantly (P < or = 0.05) reduced intermicturition, threshold and micturition pressures in chronic (3-6 weeks) spinal cord injured rats but intravesical administration (100-300 nM) was without effect. Intrathecal PACAP6-38 reduced the number and amplitude of nonvoiding bladder contractions observed after spinal cord injury (SCI). PACAP may contribute to detrusor hyperreflexia induced by SCI and PACAP antagonists may be a novel approach to reduce detrusor hyperreflexia after SCI.

Effect of intravesical Resiniferatoxin (RTX) on lower urinary tract symptoms, urodynamic parameters, and quality of life of patients with urodynamic increased bladder sensation.

OBJECTIVES: Intravesical resiniferatoxin (RTX) has been used with variable efficacy in the treatment of detrusor overactivity (DO). Patients with interstitial cystitis (IC) failed to benefit from this treatment, but a single placebo-controlled study in patients with non-IC painful bladders showed that RTX was effective in the short-term. We investigated the efficacy of intravesical RTX in patients with urgency and frequency due to increased bladder sensation. METHODS: Patients with intractable urgency and frequency, with or without urgency incontinence or bladder pain/discomfort, and with no urodynamic evidence of DO were recruited. After a single intravesical instillation of 100ml 50 nM RTX solution, patients were followed at 1, 3, and 6 mo for changes in urodynamics, bladder diary, the King's Health Questionnaire (KHQ), and degree of bladder pain. RESULTS: Fifteen patients (mean age, 52.5 yr) were treated. RTX significantly improved maximum cystometric capacity, volume at first desire to void, mean micturition volume, 24-h frequency, and daytime frequency for up to 6 mo after treatment. The overall KHQ score improved at all time points, with sustained improvements in the Symptom Severity, Incontinence Impact, and Personal Relationships domains. A >50% decrease in pain was reported by five of seven patients with painful bladders at 1 mo, but only one of seven at 6 mo. CONCLUSIONS: In our small open-label study, a single administration of intravesical RTX in patients with frequency and urgency due to increased bladder sensation significantly improved lower urinary tract symptoms, urodynamic parameters, and quality of life for up to 6 mo.

Dual, but not selective, COX-1 and COX-2 inhibitors, attenuate acetic acid-evoked bladder irritation in the anaesthetised female cat.

Non-selective cyclooxygenase (COX) inhibitors exert effects on lower urinary tract function in several species. The exact contributions of COX-1 and COX-2 isozymes have not been studied much. The present studies investigated the effects of non- and selective COX inhibitors on bladder irritation in the cat.Chloralose-anaesthetised female cats were catheterised through the bladder dome for cystometric evaluation of bladder responses to intravesical infusion of saline or acetic acid. Bladder capacity, voiding efficiency, threshold pressure, and reflex-evoked bladder contraction amplitude and duration were measured. The cat COX selectivity of the doses of inhibitors examined was determined using an in vitro whole-blood assay and analysis of plasma levels. Pretreatment with indomethacin or ketoprofen (non-selective COX inhibitors; 0.3 mg kg(-1) i.v.) inhibited acetic acid-evoked irritation (characterised by a decrease in bladder capacity in vehicle pretreated animals). FR-122047 (selective COX-1 inhibitor), NS-398 and nimesulide (selective COX-2 inhibitors; 1 and 3 mg kg(-1) i.v.) had no effects on bladder irritation. Analysis of plasma levels of the doses examined and determination of COX-1 and COX-2 inhibition in cat whole blood confirmed the reported selectivity of these compounds in this species. The present studies suggest that dual COX inhibition is required to attenuate acetic acid-evoked bladder irritation in the cat.