RESUMEN
AIMS: Neuromodulation (nerve stimulation) can produce analgesia. One form, bilateral pudendal nerve stimulation (bPNS), suppresses responses to urinary bladder distension (UBD) in hypersensitive rats. Drugs can modify this effect (eg, benzodiazepines, but not opioids, suppress bPNS effects). Prior to a clinical trial of bPNS effects on bladder pain, we felt it was prudent to survey the effects of medications commonly used in patients with bladder disorders. METHODS: Bladder hypersensitivity was produced by neonatal bladder inflammation in rat pups coupled with a second inflammatory insult as an adult. Antimuscarinic (oxybutynin), ß3 -adrenoceptor agonist (mirabegron, CL316243), α1 -adrenoceptor antagonist (tamsulosin), antidepressant (amitriptyline), muscle relaxing (baclofen), and sedative (propofol) agents were administered and effects of bPNS on responses to UBD assessed. bPNS consisted of bilateral biphasic electrical stimulation of the mixed motor/sensory component of the pudendal nerves. Visceromotor responses (VMRs; abdominal muscle contractile responses) were used as nociceptive endpoints. RESULTS: Many of these drugs directly inhibited the VMRs to UBD, but only mirabegron, at the doses employed, significantly reduced inhibitory effects of bPNS. In the presence of the other drugs, bPNS continued to produce statistically significant inhibition of VMRs to UBD. CONCLUSIONS: This study suggests that concurrent therapy with drugs used to treat bladder disorders could affect assessment of the effects of bPNS on bladder hypersensitivity. This study gives guidance to clinical trials using bPNS for the treatment of painful bladder syndromes and suggests potential clinical use of some of these medications in the treatment of these same disorders.
Asunto(s)
Cistitis/fisiopatología , Contracción Muscular/efectos de los fármacos , Nervio Pudendo/efectos de los fármacos , Agentes Urológicos/farmacología , Acetanilidas/farmacología , Animales , Terapia por Estimulación Eléctrica , Femenino , Ácidos Mandélicos/farmacología , Ratas , Ratas Sprague-Dawley , Tiazoles/farmacologíaRESUMEN
BACKGROUND: Neuromodulation, as a therapeutic modality for pain treatment, is an alternative to opioid therapies and therefore receiving increased interest and use. Neuromodulation at a peripheral nerve target, in the form of bilateral electrical pudendal nerve stimulation (bPNS), has been shown to reduce bladder hypersensitivity in rats and anecdotally reduces pain in humans with pelvic pain of urological origin. Recent studies have identified a role for spinal γ-aminobutyric acid (GABA) receptors in this effect. Concomitant medication use, such as benzodiazepines, could alter responses to neuromodulation, and so before the development of a clinical trial to confirm translation of this potential therapy, the potential interactions between acute and chronic use of benzodiazepines and bPNS were examined in a preclinical model. METHODS: Bladder hypersensitivity was produced by neonatal bladder inflammation in rat pups coupled with a second inflammatory insult as an adult. Diazepam (1-5 mg/kg intraperitoneal [i.p.]) or vehicle was administered acutely (with or without bPNS) and chronically (5 mg/kg subcutaneous [s.c.] daily for 2 weeks before the final experiment). bPNS was delivered as bilateral biphasic electrical stimulation of the mixed motor/sensory component of the pudendal nerves. Visceromotor responses (VMRs; abdominal muscle contractile responses to urinary bladder distension [UBD]) were used as nociceptive end points. Due to the profound effects of diazepam, the effect of midazolam (0.5-1.0 mg/kg i.p.) on VMRs and bPNS effects was also studied. RESULTS: Diazepam and midazolam both produced a dose-dependent, flumazenil-reversible inhibition of VMRs to UBD. bPNS resulted in statistically significant inhibition of VMRs to UBD in hypersensitive rats that had received vehicle injections. Select doses of diazepam and midazolam suppressed the inhibitory effect of bPNS on VMRs. CONCLUSIONS: This study suggests that inhibitory effects of bPNS on bladder pain could be suppressed in subjects receiving benzodiazepine therapy, suggesting that potential clinical testing of pudendal nerve stimulation for the treatment of painful bladder syndromes may be confounded by the use of benzodiazepines. Clinical assessment of other forms of neuromodulation should also be screened for impacts of benzodiazepines.
Asunto(s)
Benzodiazepinas/farmacología , Nocicepción/efectos de los fármacos , Nervio Pudendo/efectos de los fármacos , Vejiga Urinaria/efectos de los fármacos , Animales , Diazepam/farmacología , Relación Dosis-Respuesta a Droga , Estimulación Eléctrica , Femenino , Flumazenil/farmacología , Moduladores del GABA/farmacología , Midazolam/farmacología , Neuronas Motoras/efectos de los fármacos , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Células Receptoras Sensoriales/efectos de los fármacosRESUMEN
BACKGROUND AND AIMS: Hypospadias is a common congenital malformation in pediatric patients. Surgical repair of this malformation is a painful procedure and has long-term effects. Pudendal and penile nerve blocks are commonly preferred techniques for maintaining postoperative analgesia. However, the conventional landmark-based penile block technique involves numerous potential complications and provides a shorter analgesic period compared to the pudendal block. A promising ultrasound-guided dorsal penile nerve block was recently described. We aimed to compare the analgesic effectiveness of ultrasound-guided penile nerve block with that of neurostimulator-guided pudendal nerve block. METHOD: Thirty-three patients aged 1-7 years were included in this prospective, double-blinded, randomized controlled trial. Patients were divided into two groups and received either ultrasound-guided dorsal penile nerve block or neurostimulator-guided pudendal nerve block. All blocks were performed by the same two anesthesiologists, and the same surgeons performed the surgical procedures. The Face, Legs, Activity, Cry, and Consolability (FLACC) scale was used for postoperative pain management. The primary outcome of the study was time to first analgesic requirement. Secondary outcomes were FLACC scores at different time points, and types and cumulative doses of analgesic drugs. RESULTS: Dorsal penile nerve block provided longer analgesia than pudendal nerve block (32.29 ± 5.47 hours and 21.13 ± 3.53 hours, respectively; differences in mean: 11.16, 95% CI: 7.873-14.465) (P < .001). FLACC scores at the time of first analgesic requirement were significantly lower in dorsal penile nerve block group than pudendal nerve block group (median [IQR]: 2 [2-2.5] and 3 [3-5], respectively; differences in median: -1, 95% CI: -1.851 to -0.149) (P < .001). CONCLUSION: Ultrasound-guided dorsal penile nerve block provided a longer analgesic period and reduced opioid consumption compared to neurostimulator-guided pudendal nerve block.
Asunto(s)
Anestésicos Locales/administración & dosificación , Hipospadias/cirugía , Bloqueo Nervioso/métodos , Nervio Pudendo/efectos de los fármacos , Ultrasonografía , Analgesia , Niño , Preescolar , Humanos , Masculino , Pene/diagnóstico por imagen , Estudios Prospectivos , Distribución AleatoriaRESUMEN
OBJECTIVES: To compare the efficacy, safety and cost of combinations of perineal pudendal nerve block + periprostatic nerve block and intrarectal local anesthesia + periprostatic nerve block with the standard technique (periprostatic nerve block). METHODS: The study was designed as a randomized prospective controlled trial. Patients with elevated serum prostate-specific antigen values (prostate-specific antigen ≥4 ng/mL) and/or abnormal digital rectal examination findings were included in the study. Patients with anorectal diseases, chronic prostatitis, previous history of prostate biopsy and anorectal surgery were excluded from the study. A total of 148 patients (group 1 [periprostatic nerve block], n = 48; group 2 [intrarectal local anesthesia + periprostatic nerve block], n = 51; group 3 [perineal pudendal nerve block + periprostatic nerve block], n = 49) were included in the final analysis. Pain during insertion and manipulation of the transrectal ultrasound probe was recorded as visual analog scale 1, pain during penetration of the biopsy needle into the prostate and sampling was recorded as visual analog scale 2, and pain during the entire procedure recorded as visual analog scale 3. RESULTS: The mean visual analog scale 1 score was significantly lower in group 3, when compared with group 1 and group 2 (P < 0.001). There was no significant difference between the groups in terms of the mean visual analog scale 2 score. The mean visual analog scale 3 score was significantly lower in group 3 when compared with other groups (P < 0.001). The total cost for transrectal ultrasound-guided biopsy in the intrarectal local anesthesia + periprostatic nerve block group was significantly higher than the other two groups. CONCLUSIONS: The combination of perineal pudendal nerve block and periprostatic nerve block provides more effective pain control than intrarectal local anesthesia plus periprostatic nerve block and periprostatic nerve block alone, with similar complication rates and without increasing cost.
Asunto(s)
Anestesia Local/métodos , Bloqueo Nervioso/métodos , Dolor Asociado a Procedimientos Médicos/prevención & control , Neoplasias de la Próstata/diagnóstico , Anciano , Anestesia Local/efectos adversos , Anestesia Local/economía , Anestésicos Locales/administración & dosificación , Anestésicos Locales/economía , Biopsia con Aguja Gruesa/efectos adversos , Biopsia con Aguja Gruesa/economía , Biopsia con Aguja Gruesa/métodos , Análisis Costo-Beneficio , Humanos , Biopsia Guiada por Imagen/efectos adversos , Biopsia Guiada por Imagen/economía , Biopsia Guiada por Imagen/métodos , Lidocaína/administración & dosificación , Lidocaína/economía , Masculino , Persona de Mediana Edad , Bloqueo Nervioso/efectos adversos , Bloqueo Nervioso/economía , Dimensión del Dolor/estadística & datos numéricos , Dolor Asociado a Procedimientos Médicos/diagnóstico , Dolor Asociado a Procedimientos Médicos/etiología , Próstata/diagnóstico por imagen , Próstata/patología , Neoplasias de la Próstata/patología , Nervio Pudendo/efectos de los fármacos , Recto/cirugía , Ultrasonografía Intervencional/economíaRESUMEN
BACKGROUND AND AIMS: Circumcision is a frequently performed procedure in day case pediatric surgery. Dorsal penile nerve block has proven its effectiveness for the management of acute postoperative pain after circumcision. We investigated if the ultrasound-guided placement of a dorsal penile nerve block could reduce opioid requirement as compared to a landmark-based technique. METHODS: Three hundred and ten prepubertal children, aged between 52 weeks postconception and 11 years, were included in this prospective, observer-blinded, randomized controlled trial and received either a landmark- or an ultrasound-guided dorsal penile nerve block, using a caudal needle and injecting 0.1 mL/kg levobupivacaine 0.5% bilaterally. A single, experienced investigator performed all blocks. The primary endpoint was the number of patients in need of piritramide postoperatively as triggered by the Objective Pain Scale. Secondary outcome parameters included the cumulative dose of postoperatively administered opioids, the requirement to administer fentanyl intraoperatively, the need for paracetamol and ibuprofen during the first 24 postoperative hours, postoperative pain scores, the incidence of postoperative nausea and vomiting, the anesthesia induction time, and the time to discharge. RESULTS: The proportion of patients requiring postoperative piritramide did not differ significantly between both groups (Landmark: 38% vs Ultrasound: 47%, with a difference in proportion between both conditions (95% CI): 0.09 (0.2 to 0.02); P = .135). In addition, the cumulative doses of postoperative piritramide and intraoperative fentanyl, the postoperative need for paracetamol or ibuprofen, pain scores, the incidence of postoperative nausea and vomiting, and the time to discharge were not different either. However, the anesthesia induction time was significantly longer in the ultrasound-guided dorsal penile nerve block (median time [IQR]: Landmark: 11[9; 13] min vs Ultrasound: 13[11; 15] min, P < .001). CONCLUSION: Compared with the landmark-guided, the ultrasound-guided dorsal penile nerve block did not reduce the need for postoperative analgesia after circumcision in children, but was associated with an increase in the procedural time.
Asunto(s)
Circuncisión Masculina/métodos , Bloqueo Nervioso/métodos , Dolor Postoperatorio/terapia , Nervio Pudendo/efectos de los fármacos , Ultrasonografía Intervencional/métodos , Puntos Anatómicos de Referencia , Anestesia Local/métodos , Niño , Preescolar , Humanos , Lactante , Masculino , Dimensión del Dolor , Atención Perioperativa/métodos , Cuidados Posoperatorios/métodosRESUMEN
Injury to the penis resulting from zipper entrapment is a painful condition that presents a unique anesthetic challenge to the emergency physician and may even require procedural sedation for removal. In this case report, we describe successful removal of zipper entrapment from the penis of a 34-year-old patient after the application of an ultrasound-guided dorsal penile nerve block. We discuss the anatomy, sonographic features, and steps required for the nerve block procedure. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 45:589-591, 2017.
Asunto(s)
Prepucio/diagnóstico por imagen , Prepucio/lesiones , Bloqueo Nervioso/métodos , Enfermedades del Pene/patología , Nervio Pudendo/diagnóstico por imagen , Ultrasonografía Intervencional/métodos , Adulto , Anestésicos Locales/administración & dosificación , Antibacterianos/uso terapéutico , Bacitracina/uso terapéutico , Prepucio/patología , Humanos , Lidocaína/administración & dosificación , Masculino , Necrosis , Enfermedades del Pene/diagnóstico , Enfermedades del Pene/tratamiento farmacológico , Pene/diagnóstico por imagen , Pene/lesiones , Pene/inervación , Nervio Pudendo/efectos de los fármacosRESUMEN
AIM: This study examined the role of glycinergic transmission in nociceptive and non-nociceptive bladder reflexes and in inhibition of these reflexes by pudendal nerve stimulation (PNS). METHODS: Cystometrograms (CMGs) were performed in α-chloralose anesthetized cats by intravesical infusion of saline or 0.25% acetic acid (AA) to trigger, respectively, non-nociceptive or nociceptive bladder reflexes. PNS at 2 or 4 times threshold (T) intensity for inducing anal twitch was used to inhibit the bladder reflexes. Strychnine (a glycine receptor antagonist) was administered in cumulative doses (0.001-0.3 mg/kg, i.v.) at 60-120 min intervals. RESULTS: Strychnine at 0.001-0.3 mg/kg significantly (P < 0.05) increased bladder capacity and reduced contraction amplitude during saline CMGs but did not change these parameters during AA CMGs except at the 0.3 mg/kg dose which increased bladder capacity. Strychnine did not alter PNS inhibition during saline CMGs except at the highest dose at 2T intensity, but significantly (P < 0.05) suppressed PNS inhibition during AA CMGs after 0.001-0.003 mg/kg doses at 2T and 4T intensities. During AA CMGs strychnine (0.3 mg/kg) also unmasked a post-PNS excitatory effect that significantly reduced bladder capacity after termination of PNS. CONCLUSIONS: Glycinergic inhibitory neurotransmission in the central nervous system plays an unexpected role to tonically enhance the magnitude and reduce the bladder volume threshold for triggering the non-nociceptive bladder reflex. This is attributable to inhibition by glycine of another inhibitory mechanism. Glycine also has a minor role in PNS inhibition of the nociceptive bladder reflex. Neurourol. Urodynam. 35:798-804, 2016. © 2015 Wiley Periodicals, Inc.
Asunto(s)
Glicina/fisiología , Nocicepción/fisiología , Nervio Pudendo/fisiología , Reflejo/fisiología , Vejiga Urinaria/fisiología , Animales , Gatos , Estimulación Eléctrica , Femenino , Glicinérgicos/farmacología , Masculino , Contracción Muscular/efectos de los fármacos , Contracción Muscular/fisiología , Nocicepción/efectos de los fármacos , Nervio Pudendo/efectos de los fármacos , Receptores de Glicina/antagonistas & inhibidores , Reflejo/efectos de los fármacos , Estricnina/farmacología , Vejiga Urinaria/efectos de los fármacos , Vejiga Urinaria/inervaciónRESUMEN
This study examined the role of the brain stem in inhibition of bladder reflexes induced by tibial nerve stimulation (TNS) in α-chloralose-anesthetized decerebrate cats. Repeated cystometrograms (CMGs) were performed by infusing saline or 0.25% acetic acid (AA) to elicit normal or overactive bladder reflexes, respectively. TNS (5 or 30 Hz) at three times the threshold (3T) intensity for inducing toe movement was applied for 30 min between CMGs to induce post-TNS inhibition or applied during the CMGs to induce acute TNS inhibition. Inhibition was evident as an increase in bladder capacity without a change in amplitude of bladder contractions. TNS applied for 30 min between saline CMGs elicited prolonged (>2 h) poststimulation inhibition that significantly (P < 0.05) increased bladder capacity to 30-60% above control; however, TNS did not produce this effect during AA irritation. TNS applied during CMGs at 5 Hz but not 30 Hz significantly (P < 0.01) increased bladder capacity to 127.3 ± 6.1% of saline control or 187.6 ± 5.0% of AA control. During AA irritation, naloxone (an opioid receptor antagonist) administered intravenously (1 mg/kg) or directly to the surface of the rostral brain stem (300-900 µg) eliminated acute TNS inhibition and significantly (P < 0.05) reduced bladder capacity to 62.8 ± 22.6% (intravenously) or 47.6 ± 25.5% (brain stem application). Results of this and previous studies indicate 1) forebrain circuitry rostral to the pons is not essential for TNS inhibition; and 2) opioid receptors in the brain stem have a critical role in TNS inhibition of overactive bladder reflexes but are not involved in inhibition of normal bladder reflexes.
Asunto(s)
Tronco Encefálico/fisiología , Reflejo/fisiología , Nervio Tibial/fisiología , Micción/fisiología , Ácido Acético , Animales , Gatos , Estado de Descerebración/fisiopatología , Estimulación Eléctrica , Femenino , Masculino , Naloxona/farmacología , Antagonistas de Narcóticos/farmacología , Nervio Pudendo/efectos de los fármacos , Vejiga Urinaria/inervación , Vejiga Urinaria/fisiopatología , Vejiga Urinaria Hiperactiva/inducido químicamente , Vejiga Urinaria Hiperactiva/fisiopatologíaRESUMEN
This study examined the role of spinal metabotropic glutamate receptor 5 (mGluR5) in the nociceptive C-fiber afferent-mediated spinal bladder reflex and in the inhibtion of this reflex by pudendal nerve stimulation (PNS). In α-chloralose-anesthetized cats after spinal cord transection at the T9/T10 level, intravesical infusion of 0.25% acetic acid irritated the bladder, activated nociceptive C-fiber afferents, and induced spinal reflex bladder contractions of low amplitude (<50 cmH2O) and short duration (<20 s) at a smaller bladder capacity â¼80% of saline control capacity. PNS significantly (P < 0.01) increased bladder capacity from 85.5 ± 10.1 to 137.3 ± 14.1 or 148.2 ± 11.2% at 2T or 4T stimulation, respectively, where T is the threshold intensity for PNS to induce anal twitch. MTEP {3-[(2-methyl-4-thiazolyl)ethynyl]pyridine; 3 mg/kg iv, a selective mGluR5 antagonist} completely removed the PNS inhibition and significantly (P < 0.05) increased bladder capacity from 71.8 ± 9.9 to 94.0 ± 13.9% of saline control, but it did not change the bladder contraction amplitude. After propranolol (3 mg/kg iv, a ß1/ß2-adrenergic receptor antagonist) treatment, PNS inhibition remained but MTEP significantly (P < 0.05) reduced the bladder contraction amplitude from 18.6 ± 2.1 to 6.6 ± 1.2 cmH2O and eliminated PNS inhibition. At the end of experiments, hexamethonium (10 mg/kg iv, a ganglionic blocker) significantly (P < 0.05) reduced the bladder contraction amplitude from 20.9 ± 3.2 to 8.1 ± 1.5 cmH2O on average demonstrating that spinal reflexes were responsible for a major component of the contractions. This study shows that spinal mGluR5 plays an important role in the nociceptive C-fiber afferent-mediated spinal bladder reflex and in pudendal inhibition of this spinal reflex.
Asunto(s)
Músculo Liso/inervación , Inhibición Neural , Nocicepción , Nociceptores/metabolismo , Nervio Pudendo/metabolismo , Receptor del Glutamato Metabotropico 5/metabolismo , Reflejo , Nervios Espinales/metabolismo , Vejiga Urinaria Hiperactiva/metabolismo , Vejiga Urinaria/inervación , Ácido Acético , Potenciales de Acción , Animales , Gatos , Modelos Animales de Enfermedad , Antagonistas de Aminoácidos Excitadores/farmacología , Femenino , Masculino , Contracción Muscular , Fibras Nerviosas Amielínicas/efectos de los fármacos , Fibras Nerviosas Amielínicas/metabolismo , Inhibición Neural/efectos de los fármacos , Nocicepción/efectos de los fármacos , Nociceptores/efectos de los fármacos , Nervio Pudendo/efectos de los fármacos , Nervio Pudendo/fisiopatología , Piridinas/farmacología , Receptor del Glutamato Metabotropico 5/antagonistas & inhibidores , Reflejo/efectos de los fármacos , Transducción de Señal , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/fisiopatología , Nervios Espinales/efectos de los fármacos , Nervios Espinales/fisiopatología , Tiazoles/farmacología , Vértebras Torácicas , Factores de Tiempo , Vejiga Urinaria Hiperactiva/inducido químicamente , Vejiga Urinaria Hiperactiva/fisiopatología , Vejiga Urinaria Hiperactiva/terapia , UrodinámicaRESUMEN
This study examined the role of ß-adrenergic and opioid receptors in spinal reflex bladder activity and in the inhibition induced by pudendal nerve stimulation (PNS) or tibial nerve stimulation (TNS). Spinal reflex bladder contractions were induced by intravesical infusion of 0.25% acetic acid in α-chloralose-anesthetized cats after an acute spinal cord transection (SCT) at the thoracic T9/T10 level. PNS or TNS at 5 Hz was applied to inhibit these spinal reflex contractions at 2 and 4 times the threshold intensity (T) for inducing anal or toe twitch, respectively. During a cystrometrogram (CMG), PNS at 2T and 4T significantly (P < 0.05) increased bladder capacity from 58.0 ± 4.7% to 85.8 ± 10.3% and 96.5 ± 10.7%, respectively, of saline control capacity, while TNS failed to inhibit spinal reflex bladder contractions. After administering propranolol (3 mg/kg iv, a ß1/ß2-adrenergic receptor antagonist), the effects of 2T and 4T PNS on bladder capacity were significantly (P < 0.05) reduced to 64.5 ± 9.5% and 64.7 ± 7.3%, respectively, of the saline control capacity. However, the residual PNS inhibition (about 10% increase in capacity) was still statistically significant (P < 0.05). Propranolol treatment also significantly (P = 0.0019) increased the amplitude of bladder contractions but did not change the control bladder capacity. Naloxone (1 mg/kg iv, an opioid receptor antagonist) had no effect on either spinal reflex bladder contractions or PNS inhibition. At the end of experiments, hexamethonium (10 mg/kg iv, a ganglionic blocker) significantly (P < 0.05) reduced the amplitude of the reflex bladder contractions. This study indicates an important role of ß1/ß2-adrenergic receptors in pudendal inhibition and spinal reflex bladder activity.
Asunto(s)
Antagonistas Adrenérgicos beta/farmacología , Contracción Muscular/efectos de los fármacos , Naloxona/farmacología , Antagonistas de Narcóticos/farmacología , Inhibición Neural/efectos de los fármacos , Propranolol/farmacología , Nervio Pudendo/efectos de los fármacos , Reflejo/efectos de los fármacos , Nervios Espinales/efectos de los fármacos , Vejiga Urinaria/inervación , Ácido Acético/farmacología , Animales , Gatos , Modelos Animales de Enfermedad , Estimulación Eléctrica , Femenino , Masculino , Fibras Nerviosas Amielínicas/efectos de los fármacos , Nervio Pudendo/fisiopatología , Traumatismos de la Médula Espinal/fisiopatología , Nervios Espinales/fisiopatología , Nervio Tibial/efectos de los fármacos , Nervio Tibial/fisiopatología , Urodinámica/efectos de los fármacosAsunto(s)
Calcifilaxia/terapia , Criocirugía , Bloqueo Nervioso , Dolor/prevención & control , Nervio Pudendo/cirugía , Radiografía Intervencional , Nervio Ciático/cirugía , Tomografía Computarizada por Rayos X , Anestésicos Locales/administración & dosificación , Bupivacaína/administración & dosificación , Calcifilaxia/diagnóstico , Calcifilaxia/etiología , Humanos , Lidocaína/administración & dosificación , Masculino , Persona de Mediana Edad , Dolor/diagnóstico , Dolor/etiología , Dolor/fisiopatología , Cuidados Paliativos , Nervio Pudendo/diagnóstico por imagen , Nervio Pudendo/efectos de los fármacos , Nervio Pudendo/fisiopatología , Nervio Ciático/diagnóstico por imagen , Nervio Ciático/efectos de los fármacos , Nervio Ciático/fisiopatología , Resultado del TratamientoRESUMEN
Picrotoxin, an antagonist for γ-aminobutyric acid receptor subtype A (GABAA), was used to investigate the role of GABAA receptors in nociceptive and nonnociceptive reflex bladder activities and pudendal inhibition of these activities in cats under α-chloralose anesthesia. Acetic acid (AA; 0.25%) was used to irritate the bladder and induce nociceptive bladder overactivity, while saline was used to distend the bladder and induce nonnociceptive bladder activity. To modulate the bladder reflex, pudendal nerve stimulation (PNS) was applied at multiple threshold (T) intensities for inducing anal sphincter twitching. AA irritation significantly (P < 0.01) reduced bladder capacity to 34.3 ± 7.1% of the saline control capacity, while PNS at 2T and 4T significantly (P < 0.01) increased AA bladder capacity to 84.0 ± 7.8 and 93.2 ± 15.0%, respectively, of the saline control. Picrotoxin (0.4 mg it) did not change AA bladder capacity but completely removed PNS inhibition of AA-induced bladder overactivity. Picrotoxin (iv) only increased AA bladder capacity at a high dose (0.3 mg/kg) but significantly (P < 0.05) reduced 2T PNS inhibition at low doses (0.01-0.1 mg/kg). During saline cystometry, PNS significantly (P < 0.01) increased bladder capacity to 147.0 ± 7.6% at 2T and 172.7 ± 8.9% at 4T of control capacity, and picrotoxin (0.4 mg it or 0.03-0.3 mg/kg iv) also significantly (P < 0.05) increased bladder capacity. However, picrotoxin treatment did not alter PNS inhibition during saline infusion. These results indicate that spinal GABAA receptors have different roles in controlling nociceptive and nonnociceptive reflex bladder activities and in PNS inhibition of these activities.
Asunto(s)
Inhibición Neural , Dolor Nociceptivo/fisiopatología , Nociceptores/metabolismo , Umbral del Dolor , Nervio Pudendo/fisiopatología , Receptores de GABA-A/metabolismo , Reflejo , Nervios Espinales/fisiopatología , Vejiga Urinaria Hiperactiva/fisiopatología , Vejiga Urinaria/inervación , Ácido Acético , Animales , Gatos , Modelos Animales de Enfermedad , Estimulación Eléctrica , Femenino , Antagonistas del GABA/farmacología , Masculino , Inhibición Neural/efectos de los fármacos , Dolor Nociceptivo/inducido químicamente , Dolor Nociceptivo/metabolismo , Umbral del Dolor/efectos de los fármacos , Nervio Pudendo/efectos de los fármacos , Receptores de GABA-A/efectos de los fármacos , Reflejo/efectos de los fármacos , Nervios Espinales/efectos de los fármacos , Nervios Espinales/metabolismo , Vejiga Urinaria Hiperactiva/inducido químicamente , Vejiga Urinaria Hiperactiva/metabolismoRESUMEN
This study was aimed at determining the effect of duloxetine (a serotonin-norepinephrine reuptake inhibitor) on pudendal inhibition of bladder overactivity. Cystometrograms were performed on 15 cats under α-chloralose anesthesia by infusing saline and then 0.25% acetic acid (AA) to induce bladder overactivity. To inhibit bladder overactivity, pudendal nerve stimulation (PNS) at 5 Hz was applied to the right pudendal nerve at two and four times the threshold (T) intensity for inducing anal twitch. Duloxetine (0.03-3 mg/kg) was administered intravenously to determine the effect on PNS inhibition. AA irritation significantly (P < 0.01) reduced bladder capacity to 27.9 ± 4.6% of saline control capacity. PNS alone at both 2T and 4T significantly (P < 0.01) inhibited bladder overactivity and increased bladder capacity to 83.6 ± 7.6% and 87.5 ± 7.7% of saline control, respectively. Duloxetine at low doses (0.03-0.3 mg/kg) caused a significant reduction in PNS inhibition without changing bladder capacity. However, at high doses (1-3 mg/kg) duloxetine significantly increased bladder capacity but still failed to enhance PNS inhibition. WAY100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide; a 5-HT1A receptor antagonist, 0.5-1 mg/kg i.v.) reversed the suppressive effect of duloxetine on PNS inhibition and significantly (P < 0.05) increased the inhibitory effect of duloxetine on bladder overactivity but did not enhance the effect of PNS. These results indicate that activation of 5-HT1A autoreceptors on the serotonergic neurons in the raphe nucleus may suppress duloxetine and PNS inhibition, suggesting that the coadministration of a 5-HT1A antagonist drug might be useful in enhancing the efficacy of duloxetine alone and/or the additive effect of PNS-duloxetine combination for the treatment of overactive bladder symptoms.
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Inhibidores de Captación Adrenérgica/uso terapéutico , Piperazinas/uso terapéutico , Nervio Pudendo/efectos de los fármacos , Piridinas/uso terapéutico , Antagonistas de la Serotonina/uso terapéutico , Tiofenos/uso terapéutico , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Ácido Acético/administración & dosificación , Inhibidores de Captación Adrenérgica/administración & dosificación , Inhibidores de Captación Adrenérgica/farmacología , Animales , Gatos , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Clorhidrato de Duloxetina , Estimulación Eléctrica , Femenino , Masculino , Piperazinas/administración & dosificación , Piperazinas/farmacología , Nervio Pudendo/fisiología , Piridinas/administración & dosificación , Piridinas/farmacología , Serotonina/metabolismo , Antagonistas de la Serotonina/administración & dosificación , Antagonistas de la Serotonina/farmacología , Tiofenos/administración & dosificación , Tiofenos/farmacología , Vejiga Urinaria Hiperactiva/inducido químicamente , Vejiga Urinaria Hiperactiva/metabolismoRESUMEN
Urinary bladder dysfunction might be related to disturbances at different levels of the micturition reflex arc. The current study aimed to further develop and evaluate a split bladder model for detecting and analysing relaxatory signalling in the rat urinary bladder. The model allows for discrimination between effects at the efferent and the afferent side of the innervation. In in vivo experiments, the stimulation at a low frequency (1 Hz) of the ipsilateral pelvic nerve tended to evoke relaxation of the split bladder half (contralateral side; -1.0 ± 0.4 mN; n = 5), in contrast to high frequency-evoked contractions. In preparations in which the contralateral pelvic nerve was cut the relaxation occurred at a wider range of frequencies (0.5-2 Hz). In separate experiments, responses to 1 and 2 Hz were studied before and after intravenous injections of propranolol (1 mg/kg IV). The presence of propranolol significantly shifted the relaxations into contractions. Also, electrical stimulation of the ipsilateral pudendal nerve evoked relaxations of similar magnitude as for the pelvic stimulations, which were also affected by propranolol. In control in vitro experiments, substances with ß-adrenoceptor agonism, in contrast to a selective α-agonist, evoked relaxations. The current study shows that the split bladder model can be used for in vivo studies of relaxations. In the model, reflex-evoked sympathetic responses caused relaxations at low intensity stimulation. The involvement of ß-adrenoceptors is supported by the sensitivity to propranolol and by the in vitro observations.
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Estimulación Eléctrica , Propranolol , Nervio Pudendo , Vejiga Urinaria , Animales , Vejiga Urinaria/inervación , Vejiga Urinaria/fisiología , Vejiga Urinaria/efectos de los fármacos , Nervio Pudendo/fisiología , Nervio Pudendo/efectos de los fármacos , Ratas , Propranolol/farmacología , Femenino , Relajación Muscular/efectos de los fármacos , Relajación Muscular/fisiología , Ratas Wistar , Pelvis/inervación , Antagonistas Adrenérgicos beta/farmacología , Masculino , Ratas Sprague-DawleyAsunto(s)
Bloqueo Nervioso/métodos , Dolor Postoperatorio/patología , Nervio Pudendo/efectos de los fármacos , Neoplasias del Recto/cirugía , Grabación en Video , Neoplasias del Ano/cirugía , Bupivacaína/administración & dosificación , Femenino , Humanos , Masculino , Dimensión del Dolor , Enfermedades del Recto/patología , Enfermedades del Recto/cirugíaRESUMEN
Moderate intravenous (IV) sedation combined with local anesthesia is common for outpatient oral surgery procedures. An ideal sedative agent must be safe and well tolerated by patients and practitioners. This study evaluated fospropofol, a relatively new sedative/hypnotic, in comparison to midazolam, a commonly used benzodiazepine, for IV moderate sedation during oral and maxillofacial surgery. Sixty patients were randomly assigned to either the fospropofol or the midazolam group. Each participant received 1 µg/kg of fentanyl prior to administration of the selected sedative. Those in the fospropofol group received an initial dose of 6.5 mg/kg, with 1.6 mg/kg supplemental doses as needed. Those in the midazolam group received initial doses of 0.05 mg/kg, followed by 0.02 mg/kg supplemental doses. The quality of sedation in each patient was evaluated with regard to (a) onset of sedation, maintenance, and recovery profile; (b) patient and surgeon satisfaction; and (c) hemodynamic stability and adverse effects. The fospropofol group demonstrated shorter physical recovery times than midazolam patients, taking a mean of 11.6 minutes versus 18.4 minutes for physical recovery (P = .007). Cognitive recovery comparison did not find any difference with a mean of 7.5 minutes versus 8.8 minutes between the 2 drug groups (P = .123). The fospropofol group had a higher rate of local anesthetic injection recall (90.5 vs 44.4%, P = .004). Other parameters of recall were comparable. Two adverse effects demonstrated significance, with more patients in the midazolam group experiencing tachycardia (48.2 vs 9.4%, P = .001), and more patients in the fospropofol group experiencing perineal discomfort (40.6 vs 0, P < .001). No significant difference was found in any other measures of sedation safety, maintenance, or satisfaction. Fospropofol, when administered intravenously by a dentist anesthesiologist at the indicated dose in this study, appears to be a safe, well-tolerated alternative to midazolam for intravenous moderate sedation during minor oral surgery procedures.
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Anestesia Dental/métodos , Sedación Consciente/métodos , Hipnóticos y Sedantes , Midazolam , Propofol/análogos & derivados , Adyuvantes Anestésicos , Adolescente , Adulto , Atención Ambulatoria , Análisis de Varianza , Periodo de Recuperación de la Anestesia , Anestesia Dental/efectos adversos , Anestesia Intravenosa/efectos adversos , Anestesia Intravenosa/métodos , Anestésicos Locales , Sedación Consciente/efectos adversos , Femenino , Fentanilo , Humanos , Hipnóticos y Sedantes/efectos adversos , Hipnóticos y Sedantes/farmacología , Masculino , Memoria , Midazolam/efectos adversos , Midazolam/farmacología , Persona de Mediana Edad , Satisfacción del Paciente , Propofol/efectos adversos , Propofol/farmacología , Nervio Pudendo/efectos de los fármacos , Encuestas y Cuestionarios , Taquicardia/etiología , Adulto JovenAsunto(s)
Lidocaína , Bloqueo Nervioso/métodos , Dimensión del Dolor , Neoplasias de la Próstata/patología , Nervio Pudendo/efectos de los fármacos , Anciano , Anestesia/métodos , Anestésicos Locales/farmacología , Biopsia con Aguja , Humanos , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Manejo del Dolor/métodos , Perineo/patología , Perineo/cirugía , Próstata/efectos de los fármacos , Próstata/inervación , Neoplasias de la Próstata/cirugíaRESUMEN
OBJECTIVE: To examine the evolution of pain and the duration of numbness after neural blockade of the pudendal nerve in women with pudendal neuralgia and correlate with clinical and historical data. DESIGN: Prospective, single arm, open label study. SETTING: University hospital and outpatient clinic. SUBJECTS: Eighty-two adult female patients were recruited from November 8, 2008 to February 14, 2010. Patients were selected based on the presence of spontaneous or provoked pain in the distribution of the pudendal nerve. INTERVENTIONS: Subjects underwent a standardized pudendal nerve block. OUTCOME MEASURES: Visual analog pain scores and the presence of numbness were recorded before and for 64 hours after the pudendal nerve block. A complete clinical history and examination were documented. RESULTS: Sixty-six patients completed the study. About 86.9% had a reduction in one or more pain symptom, while 44.3% found that more than one of their pain symptoms did not return. About 69.7% of patients reported numbness lasting up to 16 hours or longer. Previous gynecological surgery was recorded in 75.8%, previous traumatic obstetric events in 47.0% of cases. Prolonged history of pain correlated with a reduced chance of positive outcome of the pudendal nerve block. CONCLUSION: In patients with pudendal neuralgia, the pudendal nerve block has a variable response, but may have a beneficial effect in a subset of women. Surgical and obstetrical trauma are common historical antecedents.
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Bloqueo Nervioso/métodos , Nervio Pudendo/efectos de los fármacos , Nervio Pudendo/fisiopatología , Neuralgia del Pudendo/tratamiento farmacológico , Neuralgia del Pudendo/fisiopatología , Adolescente , Adulto , Anciano , Candidiasis Vulvovaginal/complicaciones , Candidiasis Vulvovaginal/fisiopatología , Estudios de Cohortes , Femenino , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Nervio Pudendo/lesiones , Neuralgia del Pudendo/etiología , Factores de Tiempo , Adulto JovenRESUMEN
Background and Objectives. Several anesthesia techniques were applied to hemorrhoidectomy, but postoperative pain and urinary retention were still two unsolved problems. The aim of this prospective randomized study was to evaluate the effect of ultrasound-guided pudendal nerve block (PNB) combined with deep sedation compared to spinal anesthesia for hemorrhoidectomy. Methods. One hundred and twenty patients undergoing Milligan-Morgan hemorrhoidectomy were randomized to receive PNB combined with deep sedation using propofol (Group PNB, n = 60) or spinal anesthesia (Group SA, n = 60). Pain intensity was assessed using the visual analogue scale (0: no pain to 10: worst possible pain). The primary outcome was pain scores recorded at rest at 3, 6, 12, 24, 36, and 48 h and on walking at 12, 24, 36, and 48 h postoperatively. Secondary outcomes were analgesic consumption, side effects, and patient satisfaction after surgery. Results. Ultrasound-guided bilateral PNB combined with deep sedation using propofol could successfully be applied to Milligan-Morgan hemorrhoidectomy. Postoperative pain intensity was significantly lower in Group PNB compared to Group SA at rest at 3, 6, 12, 24, 36, and 48 h (p < 0.001) and during mobilization at 12, 24, 36, and 48 h (p < 0.001) postoperatively. Sufentanil consumption in Group PNB was significantly lower than that in Group SA, during 0-24 h (p < 0.001) and during 24-48 h (p < 0.001) postoperatively. Urinary retention was significantly lower in Group PNB compared to Group SA (6.9% vs 20%, p=0.034). The patients in Group PNB had higher satisfaction compared to Group SA (p < 0.001). Conclusions. Ultrasound-guided PNB combined with propofol sedation is an effective anesthesia technique for Milligan-Morgan hemorrhoidectomy.
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Anestesia Raquidea/métodos , Sedación Profunda/métodos , Hemorreoidectomía/métodos , Bloqueo Nervioso/métodos , Propofol/uso terapéutico , Nervio Pudendo/efectos de los fármacos , Nervio Pudendo/diagnóstico por imagen , Ultrasonografía Intervencional/métodos , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dolor Postoperatorio/tratamiento farmacológico , Propofol/farmacología , Estudios Prospectivos , Adulto JovenRESUMEN
INTRODUCTION: More than 200 million women and girls have undergone genital mutilation. Clitoral reconstruction (CR) can improve the quality of life of some of them, but is accompanied by significant postoperative pain. OBJECTIVE: Assess and describe the management of postoperative pain after CR, and the practices amongst specialists in different countries. METHODS: Between March and June 2020, 32 surgeons in 14 countries (Germany, Austria, Belgium, Burkina Faso, Canada, Ivory Coast, Egypt, Spain, United States of America, France, the Netherlands, Senegal, Switzerland, Sweden) responded to an online questionnaire on care and analgesic protocols for CR surgery. RESULTS: At day 7 post CR, 97% of the surgeons observed pain amongst their patients, which persisted up to 1 month for half of them. 22% of the participants reported feeling powerless in the management of such pain. The analgesic treatments offered are mainly step II and anti-inflammatory drugs (61%). Screening for neuropathic pain is rare (3%), as is the use of pudendal nerve block, used by 8% of the care providers and only for a small percentage of women. CONCLUSION: Pain after CR is frequent, long-lasting, and potentially an obstacle for the women who are willing to undergo clitoral surgery and also their surgeons. Most surgeons from different countries follow analgesic protocols that do not use the full available therapeutic possibilities. Early treatment of neuropathic pain, optimisation of dosing of standard analgesics, addition of opioids, use of acupuncture, and routine intraoperative use of pudendal nerve block might improve the management of pain after CR.