RESUMEN
BACKGROUND: Verbascoside, a representative phenylethanoid glycoside, is widely distributed in plants and has various activities beneficial for human health. Although systemically administered verbascoside has an antinociceptive effect, little is known about the site and mechanism of its activity. The aim of the present study was to determine whether verbascoside attenuates neuropathic pain in the spinal cord and which pain regulatory systems are involved. METHODS: Chronic constriction injury of the sciatic nerve was introduced to male Sprague Dawley rats. The effects of intrathecal administration of verbascoside and its components (caffeic acid and hydroxytyrosol) on mechanical hyperalgesia and cold hyperalgesia were examined using the electronic von Frey test and cold-plate test, respectively. Several antagonists of spinal pain processing receptors were administered intrathecally to evaluate their effects on the antihyperalgesic action of verbascoside. A rotarod test was performed to assess the effects on motor coordination. RESULTS: Verbascoside attenuated mechanical and cold hyperalgesia and affected motor performance in a dose-dependent manner. Caffeic acid suppressed hyperalgesia only at high doses, whereas hydroxytyrosol did not affect hyperalgesia. The inhibitory effects of verbascoside on hyperalgesia and motor coordination were reversed by naloxone, a µ-opioid receptor antagonist. CONCLUSIONS: These findings imply that verbascoside exerts an antihyperalgesic effect by activating µ-opioid receptors in the spinal cord, and that neither caffeic acid nor hydroxytyrosol alone mediates its activity. Verbascoside shows promise for the treatment of neuropathic pain. SIGNIFICANCE: Currently available treatments for neuropathic pain have limited efficacy in most patients. Some natural products have favourable biological activities for long-term administration such as antioxidative and neuroprotective effects. Verbascoside inhibits spinal nociceptive transmission without serious side effects to the same degree as gabapentin, a first-line remedy for neuropathic pain. Natural products may be promising candidates for novel treatments of neuropathic pain.
Asunto(s)
Productos Biológicos , Neuralgia , Analgésicos/farmacología , Analgésicos/uso terapéutico , Animales , Productos Biológicos/uso terapéutico , Constricción , Modelos Animales de Enfermedad , Glucósidos , Humanos , Hiperalgesia/tratamiento farmacológico , Masculino , Neuralgia/tratamiento farmacológico , Fenoles , Ratas , Ratas Sprague-Dawley , Receptores Opioides , Receptores Opioides muRESUMEN
Punicalagin, a natural polyphenolic compound classified as an ellagitannin, is a major ingredient of pomegranate (Punica granatum L.). Punicalagin has potent antioxidant and anti-inflammatory effects. Although the antinociceptive effects of orally administered pomegranate extracts have been reported, little is known about the effect of punicalagin on nociceptive transmission in the central nervous system. We examined whether punicalagin ameliorates neuropathic pain and inflammatory pain in the spinal cord. Male Sprague-Dawley rats were subjected to chronic constriction injury (CCI) of the sciatic nerve, and an intrathecal catheter was implanted for drug administration. The electronic von Frey test and cold-plate test were performed in CCI rats to evaluate mechanical and cold hyperalgesia in neuropathic pain, and the formalin test was performed in normal rats to evaluate acute and persistent inflammatory pain. An open-field test was conducted to explore whether punicalagin affects locomotor activity in CCI rats. Punicalagin administered intrathecally attenuated mechanical and cold hyperalgesia to the same degree as gabapentin in CCI rats and reduced pain-related behaviors in both the early and late phases in formalin-injected rats. Punicalagin did not affect motor function. These results suggest that punicalagin exerts an antinociceptive effect in the spinal cord without motor deficit, thus showing therapeutic potential for neuropathic pain and inflammatory pain.
Asunto(s)
Taninos Hidrolizables , Neuralgia , Analgésicos/uso terapéutico , Animales , Taninos Hidrolizables/uso terapéutico , Hiperalgesia/tratamiento farmacológico , Inyecciones Espinales , Masculino , Neuralgia/tratamiento farmacológico , Ratas , Ratas Sprague-Dawley , Médula EspinalRESUMEN
BACKGROUND: The endocannabinoid system modulates a wide variety of pain conditions. Systemically administered AM404, an endocannabinoid reuptake inhibitor, exerts antinociceptive effects via activation of the endocannabinoid system. However, the mechanism and site of AM404 action are not fully understood. Here, we explored the effect of AM404 on neuropathic pain at the site of the spinal cord. METHODS: Male Sprague-Dawley rats were subjected to chronic constriction injury (CCI) of the sciatic nerve. The effects of intrathecal administration of AM404 on mechanical and cold hyperalgesia were examined using the electronic von Frey test and cold plate test, respectively. Motor coordination was assessed using the rotarod test. To understand the mechanisms underlying the action of AM404, we tested the effects of pretreatment with the cannabinoid type 1 (CB1) receptor antagonist AM251, CB2 receptor antagonist AM630, and transient receptor potential vanilloid type 1 (TRPV1) antagonist capsazepine. RESULTS: AM404 attenuated mechanical and cold hyperalgesia with minimal effects on motor coordination. AM251 significantly inhibited the antihyperalgesic action of AM404, whereas capsazepine showed a potentiating effect. CONCLUSIONS: These results indicate that AM404 exerts antihyperalgesic effects primarily via CB1, but not CB2, receptor activation at the site of the spinal cord. TRPV1 receptors appear to play a pronociceptive role in CCI rats. The endocannabinoid reuptake inhibitor may be a promising candidate treatment for neuropathic pain.
Asunto(s)
Ácidos Araquidónicos/administración & dosificación , Endocannabinoides/metabolismo , Neuralgia/tratamiento farmacológico , Médula Espinal/efectos de los fármacos , Animales , Capsaicina/análogos & derivados , Capsaicina/farmacología , Constricción , Modelos Animales de Enfermedad , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/metabolismo , Indoles/farmacología , Masculino , Neuralgia/metabolismo , Dimensión del Dolor/métodos , Piperidinas/farmacología , Pirazoles/farmacología , Ratas , Ratas Sprague-Dawley , Receptor Cannabinoide CB1/metabolismo , Receptor Cannabinoide CB2/metabolismo , Prueba de Desempeño de Rotación con Aceleración Constante/métodos , Médula Espinal/metabolismo , Canales Catiónicos TRPV/metabolismoRESUMEN
The descending serotonergic pathway, from the brainstem to spinal cord, modulates various aspects of pain processing. The spinal 5-hydroxytryptamine (5-HT)1A and 5-HT2A receptors play pivotal roles in pain modulation. Perospirone is a novel atypical antipsychotic that serves as a 5-hydroxytryptamine (5-HT)1A receptor agonist, a 5-HT2A receptor antagonist, and a dopamine D2 receptor antagonist. Little is known about the effect of perospirone on pain transmission. Here, we explored whether perospirone attenuated neuropathic and inflammatory pain in the spinal cord. A chronic constriction injury to the sciatic nerve was induced in male Sprague-Dawley rats. We evaluated the effects of intrathecal administration of perospirone (10, 20, or 40 µg) on mechanical and cold hyperalgesia using the electronic von Frey and cold plate tests, respectively. Normal rats were assessed in terms of inflammatory nociception using the formalin test and for motor coordination employing the rotarod test. To define the mechanism underlying the action of perospirone, the effects of intrathecal pretreatment with the 5-HT1A receptor antagonist WAY-100635, the 5-HT2A/2C receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-aminopropane (DOI), and the dopamine D2 receptor agonist sumanirole on perospirone action were examined using the electronic von Frey test and cold plate test. Perospirone dose-dependently alleviated mechanical and cold hyperalgesia, but not inflammatory nociception in the spinal cord, and affected motor coordination. WAY-100635 reversed the antihyperalgesic action of perospirone significantly, but neither DOI nor sumanirole exhibited such an effect. We conclude that perospirone attenuates mechanical and cold hyperalgesia principally via 5-HT1A receptor activation in the spinal cord, and the agent is a promising novel candidate for neuropathic pain relief.
Asunto(s)
Analgésicos/administración & dosificación , Hiperalgesia/tratamiento farmacológico , Inyecciones Espinales/métodos , Isoindoles/administración & dosificación , Neuralgia/tratamiento farmacológico , Tiazoles/administración & dosificación , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Hiperalgesia/metabolismo , Masculino , Neuralgia/metabolismo , Dimensión del Dolor/efectos de los fármacos , Piperazinas/farmacología , Piridinas/farmacología , Ratas , Ratas Sprague-Dawley , Receptor de Serotonina 5-HT1A/metabolismo , Prueba de Desempeño de Rotación con Aceleración Constante , Antagonistas del Receptor de Serotonina 5-HT1/farmacología , Transducción de Señal/efectos de los fármacosRESUMEN
Chronic pain conditions such as neuropathic pain and persistent inflammatory pain are difficult to manage. Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors modulate nociceptive processing at the spinal dorsal horn. Previous studies have shown that intrathecal AMPA receptor antagonists exert antinociception in various pain states. Perampanel is a selective, noncompetitive inhibitor of the AMPA receptor and used clinically as an antiepileptic drug. Little is known about antinociceptive action of perampanel in the spinal cord. Here, we explored whether intrathecal perampanel attenuates neuropathic and inflammatory pain. A chronic constriction injury (CCI) to the sciatic nerve was induced in male Sprague-Dawley rats. We evaluated the effects of intrathecal perampanel (10, 30, or 100 µg) on mechanical and cold hyperalgesia using the electronic von Frey and cold plate tests, respectively. Normal rats were assessed in terms of inflammatory nociception using the formalin test, and motor function employing the rotarod test. In the CCI rats, spinally applied perampanel inhibited mechanical and cold hyperalgesia dose-dependently. In normal rats, perampanel remarkably suppressed the early- and late-phase responses in the formalin test, and it weakly affected motor performance for a short period at the highest dose. These results suggest that perampanel exerts antinociceptive actions on neuropathic and persistent inflammatory pain in the spinal cord. Perampanel may be safe and beneficial remedy for patients with such pain conditions. In addition, AMPA receptor can be a promising target for treatment of chronic pain.
Asunto(s)
Dolor Crónico/tratamiento farmacológico , Neuralgia/tratamiento farmacológico , Traumatismos de los Nervios Periféricos/tratamiento farmacológico , Piridonas/administración & dosificación , Receptores AMPA/antagonistas & inhibidores , Animales , Dolor Crónico/inmunología , Dolor Crónico/patología , Modelos Animales de Enfermedad , Humanos , Inyecciones Espinales , Masculino , Neuralgia/inmunología , Neuralgia/patología , Nitrilos , Nocicepción/efectos de los fármacos , Traumatismos de los Nervios Periféricos/complicaciones , Traumatismos de los Nervios Periféricos/inmunología , Ratas , Nervio Ciático/lesiones , Médula Espinal/efectos de los fármacos , Médula Espinal/inmunología , Médula Espinal/patologíaRESUMEN
Glycinergic transmission has an important role in regulating nociception in the spinal cord. The glycine transporter-2 (GlyT2) is localized at presynaptic terminals of glycinergic neurons and eliminates glycine from the synaptic cleft to terminate glycinergic transmission. Systemic and intrathecal administration of GlyT2 inhibitors alleviate various types of pain. Although the GlyT2s and glycine receptors are widely distributed in the central nervous system, little is known about the role of glycinergic transmission in pain perception at supraspinal regions. The present study examined the antinociceptive effect of intracerebroventricular (i.c.v.) administration of the selective GlyT2 inhibitor ALX1393 on inflammatory and neuropathic pain in experimental models. For i.c.v. administration, a guide cannula was implanted into the right lateral ventricle of male Sprague-Dawley rats. Normal rats were used to assess inflammatory nociception using the formalin test and motor function using the rotarod test. Chronic constriction injury (CCI) to the sciatic nerve was induced in the rats. The CCI rats were then used to assess mechanical, cold, and thermal hyperalgesia using the electronic von Frey test, cold plate test, and the plantar test, respectively. ALX1393 (25, 50, and 100 µg) was administered i.c.v. to examine its effects on supraspinal antinociception. Supraspinal ALX1393 in normal rats suppressed the late-phase response in the formalin test but did not affect motor performance. In the CCI rats, ALX1393 inhibited mechanical and cold hyperalgesia in a dose-dependent manner. The antihyperalgesic effects of ALX1393 (100 µg) were reversed completely by i.c.v. pretreatment with a glycine receptor antagonist strychnine (10 µg). These results suggest that GlyT2 contributes to nociceptive transmission at supraspinal level and that the selective GlyT2 inhibitor is a promising candidate for the treatment of inflammatory and neuropathic pain without causing motor dysfunction.
Asunto(s)
Proteínas de Transporte de Glicina en la Membrana Plasmática/antagonistas & inhibidores , Inflamación/tratamiento farmacológico , Neuralgia/tratamiento farmacológico , Dolor/complicaciones , Dolor/tratamiento farmacológico , Serina/análogos & derivados , Analgésicos/administración & dosificación , Analgésicos/farmacología , Analgésicos/uso terapéutico , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Hiperalgesia/complicaciones , Hiperalgesia/tratamiento farmacológico , Inflamación/complicaciones , Infusiones Intraventriculares , Masculino , Dimensión del Dolor , Ratas , Prueba de Desempeño de Rotación con Aceleración Constante , Serina/administración & dosificación , Serina/antagonistas & inhibidores , Serina/farmacología , Serina/uso terapéutico , Estricnina/farmacologíaRESUMEN
Luteolin, a major component of flavones, is known to have various physiological properties. Although luteolin reportedly has an antinociceptive effect on acute and inflammatory pain, little is known about its effect on neuropathic pain. The aim of the present study was to determine whether luteolin could ameliorate hyperalgesia in the central nervous system using a neuropathic pain model. Chronic constriction injury to the sciatic nerve was induced in male Sprague-Dawley rats. Luteolin (0.1-1.5 mg) was administered intrathecally or intracerebroventricularly to examine the central effects on mechanical, thermal, and cold hyperalgesia using the electronic von Frey test, plantar test, and cold plate test, respectively. A rotarod test was also performed to assess motor function in normal rats. Spinally applied luteolin dose-dependently attenuated mechanical and cold hyperalgesia, but it had no effect on thermal hyperalgesia. At the highest dose, luteolin affected motor performance. The spinal action of luteolin on mechanical hyperalgesia was inhibited by intrathecal pretreatment with the γ-aminobutyric acidA (GABAA) receptor antagonist bicuculline and µ-opioid receptor antagonist naloxone, but not by intrathecal pretreatment with either the benzodiazepine receptor antagonist flumazenil or glycine receptor antagonist strychnine. Supraspinal application of luteolin had no antihyperalgesic effects in any test. These findings suggest that luteolin ameliorates mechanical and cold hyperalgesia at least in part by activating GABAA receptors in a flumazenil-insensitive manner and µ-opioid receptors in the spinal cord, but that the supraspinal regions are unlikely to contribute to the antihyperalgesic action of luteolin. Luteolin could be a candidate therapeutic agent for neuropathic pain.
Asunto(s)
Analgésicos/farmacología , Luteolina/farmacología , Neuralgia/tratamiento farmacológico , Analgésicos/administración & dosificación , Animales , Modelos Animales de Enfermedad , Hiperalgesia/tratamiento farmacológico , Infusiones Intraventriculares , Inyecciones Espinales , Luteolina/administración & dosificación , Masculino , Actividad Motora/efectos de los fármacos , Dimensión del Dolor , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
Chlorogenic acid (CGA), one of the most abundant dietary polyphenols, is known to have various physiological properties. Although CGA is reported to have an antinociceptive effect on acute and inflammatory pain, little is known about its effect on neuropathic pain or its action site. The aim of the present study was to determine whether intrathecally administered CGA can ameliorate hyperalgesia in a neuropathic pain model. Chronic constriction injury to the sciatic nerve was induced in male Sprague-Dawley rats. CGA (0.5, 1, or 2mg) was administered intrathecally to examine the effects on mechanical, thermal, and cold hyperalgesia using the electronic von Frey test, plantar test, and cold plate test, respectively. A rotarod test was also performed to assess motor function. To identify the neurotransmitter pathway involved in the spinal action of CGA, the present study examined the effect of intrathecal pretreatment with several antagonists of spinal pain processing receptors on the action of CGA in the electronic von Frey test and cold plate test. Spinally applied CGA dose-dependently alleviated mechanical and cold hyperalgesia. Conversely, CGA had no effect on thermal hyperalgesia. At the highest dose, CGA affected motor performance. The antihyperalgesic action of CGA was partially reversed by bicuculline, an γ-aminobutyric acidA (GABAA) receptor antagonist, at a dose that did not affect baseline behavioral responses. These findings suggest that CGA ameliorates mechanical and cold hyperalgesia partly by activating GABAergic transmission in the spinal cord, and that CGA may be useful for novel treatments for neuropathic pain.
Asunto(s)
Analgésicos/uso terapéutico , Ácido Clorogénico/uso terapéutico , Hiperalgesia/tratamiento farmacológico , Neuralgia/tratamiento farmacológico , Analgésicos/administración & dosificación , Animales , Ácido Clorogénico/administración & dosificación , Frío , Modelos Animales de Enfermedad , Calor , Inyecciones Espinales , Masculino , Ratas , Ratas Sprague-Dawley , Prueba de Desempeño de Rotación con Aceleración ConstanteRESUMEN
BACKGROUND: Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the mammalian central nervous system. GABAergic transmission has an important role in regulating nociception at the spinal dorsal horn. It is terminated by rapid uptake of the neurotransmitter from the synaptic cleft into neurons and glial cells, via specific GABA transporters (GATs). Among the 4 GATs, GAT-3 has the greatest expression in central nervous system regions closely associated with nociceptive transmission, including the spinal cord. In this study, we examined the antinociceptive effect of intrathecal administration of a selective GAT-3 inhibitor, SNAP5114, on acute, inflammatory, and neuropathic pain in experimental models. METHODS: Male Sprague-Dawley rats were used to assess thermal, mechanical, and chemical nociception in the tail flick and hotplate tests, the paw pressure test, and the formalin test. A rotarod test was performed to assess motor function. Chronic constriction injury to the sciatic nerve was induced in the rats. The electronic von Frey test and the plantar test were then performed to assess mechanical allodynia and thermal hyperalgesia. SNAP5114 (10, 50, 100, or 200 µg) was administered intrathecally to examine antinociceptive activity. To confirm whether the action of SNAP5114 was mediated by GABAergic transmission, the GABAA receptor antagonist bicuculline (0.3 µg) or the GABAB receptor antagonist CGP35348 (30 µg) was administered intrathecally before 200 µg of SNAP5114 in the tail flick test, the formalin test, and the electronic von Frey test. RESULTS: Spinally applied SNAP5114 in normal rats dose-dependently prolonged withdrawal latencies in the tail flick test and suppressed the late-phase response in the formalin test. SNAP5114 did not affect motor performance. In the chronic constriction injury rats, SNAP5114 inhibited mechanical allodynia dose-dependently. The antinociceptive action of SNAP5114 was partially reversed by bicuculline or CGP35348 at doses at which the antagonist alone did not affect baseline behavioral responses. CONCLUSIONS: These results suggest that SNAP5114 exerts antinociceptive effects by activating GABAA and GABAB receptors in the spinal cord. The GAT-3 inhibitor may prove useful in treatment of various painful conditions.
Asunto(s)
Analgésicos , Anisoles/farmacología , Proteínas Transportadoras de GABA en la Membrana Plasmática/efectos de los fármacos , Ácidos Nipecóticos/farmacología , Dolor/tratamiento farmacológico , Dolor Agudo/tratamiento farmacológico , Animales , Anisoles/uso terapéutico , Conducta Animal/efectos de los fármacos , Dolor Crónico/tratamiento farmacológico , Constricción Patológica/complicaciones , Constricción Patológica/patología , Relación Dosis-Respuesta a Droga , Alimentos , Formaldehído , Antagonistas del GABA/farmacología , Calor , Inyecciones Espinales , Masculino , Ácidos Nipecóticos/uso terapéutico , Dimensión del Dolor/efectos de los fármacos , Estimulación Física , Equilibrio Postural/efectos de los fármacos , Presión , Desempeño Psicomotor/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Tiempo de Reacción/efectos de los fármacosRESUMEN
Hypotaurine is an intermediate in taurine biosynthesis from cysteine in astrocytes. Although hypotaurine functions as an antioxidant and organic osmolyte, its physiological role in the central nervous system remains unclear. This study used behavioral assessments to determine whether hypotaurine influenced nociceptive transmission in acute, inflammatory, and neuropathic pain. The tail flick, paw pressure, and formalin tests were performed in male Sprague-Dawley rats to examine the effects of the intrathecal administration of hypotaurine (100, 200, 400, 600 µg) on thermal, mechanical, and chemical nociception. Chronic constriction injury (CCI) to the sciatic nerve was induced in the rats, and the electronic von Frey test and plantar test were performed to assess the effects on neuropathic pain. To determine which neurotransmitter pathway(s) was involved in the action of hypotaurine, in this study, we examined how the antagonists of spinal pain processing receptors altered the effect of 600 µg hypotaurine. To explore whether hypotaurine affected motor performance, the Rotarod test was conducted. Hypotaurine had antinociceptive effects on thermal, mechanical, and chemical nociception in the spinal cord. In CCI rats, hypotaurine alleviated mechanical allodynia and thermal hyperalgesia. These effects were reversed completely by pretreatment with an intrathecal injection of strychnine, a glycine receptor antagonist. Conversely, hypotaurine did not affect motor performance. This study demonstrated that intrathecal hypotaurine suppressed acute, inflammatory, and neuropathic pain. Hypotaurine may regulate nociceptive transmission physiologically by activating glycinergic neurons in the spinal cord, and it is a promising candidate for treating various pain states.
Asunto(s)
Analgésicos/administración & dosificación , Neuralgia/tratamiento farmacológico , Dolor Nociceptivo/tratamiento farmacológico , Taurina/análogos & derivados , Analgésicos/farmacología , Animales , Conducta Animal/efectos de los fármacos , Inyecciones Espinales , Masculino , Umbral del Dolor/efectos de los fármacos , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Nervio Ciático/efectos de los fármacos , Nervio Ciático/lesiones , Nervio Ciático/cirugía , Médula Espinal/efectos de los fármacos , Taurina/administración & dosificación , Taurina/farmacologíaRESUMEN
PURPOSE: Taurine is the most abundant amino acid in many tissues. Although taurine has been shown to be antinociceptive, in this report, our focus is to elucidate the mechanism and action site on neuropathic pain. This study used behavioural assessments to determine whether taurine attenuates neuropathic pain in the spinal cord. METHODS: Chronic constriction injury (CCI) to the sciatic nerve and streptozotocin-induced diabetic neuropathy were introduced to male Sprague-Dawley rats. We then assessed the antinociceptive effect of spinal injections of taurine (100, 200, 400, or 800 µg) using electronic von Frey, paw pressure, and plantar tests. To explore the effect of taurine on motor function, a rotarod test was performed, and in order to determine which neurotransmitter pathway is involved in taurine's action, we examined how several antagonists of spinal pain processing receptors altered the effect of taurine 400 µg in a paw pressure test. RESULTS: Taurine alleviated mechanical allodynia, mechanical hyperalgesia, and thermal hyperalgesia in CCI rats and suppressed mechanical allodynia and hyperalgesia in diabetic rats. Significant effects were observed at 200 µg in both models. On the other hand, taurine dose-dependently affected motor performance, and a significant effect was seen at 400 µg. The antinociceptive effects were reversed completely by pretreatment with an intrathecal injection of strychnine, a glycine receptor antagonist. CONCLUSION: The present study demonstrated that intrathecal administration of taurine attenuates different models of neuropathic pain, and these effects seem to be mediated by the activation of glycinergic neurotransmission. These findings suggest that taurine may be a candidate remedy for neuropathic pain.
Asunto(s)
Analgésicos/farmacología , Neuropatías Diabéticas/tratamiento farmacológico , Neuralgia/tratamiento farmacológico , Taurina/farmacología , Analgésicos/administración & dosificación , Animales , Conducta Animal/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Hiperalgesia/tratamiento farmacológico , Inyecciones Espinales , Masculino , Ratas , Ratas Sprague-Dawley , Nervio Ciático/lesiones , Taurina/administración & dosificaciónRESUMEN
BACKGROUND: Glycinergic neurons in the spinal dorsal horn have been implicated in the inhibition of spinal pain processing in peripheral inflammation and chronic pain states. Neuronal isoform glycine transporter-2 (GlyT2) reuptakes presynaptically released glycine and regulates the glycinergic neurotransmission. In this study, we examined whether a selective GlyT2 inhibitor, ALX1393, elicits an antinociceptive effect in a rat acute pain model. METHODS: Male Sprague-Dawley rats were implanted with a catheter intrathecally. The effects of intrathecal administration of ALX1393 (4, 20, or 40 microg) on thermal, mechanical, and chemical nociception were evaluated by tail flick, hot plate, paw pressure, and formalin tests. Furthermore, to explore whether ALX1393 affects motor function, a rotarod test was performed. RESULTS: ALX1393 exhibited antinociceptive effects on the thermal and mechanical stimulations in a dose-dependent manner. The maximal effect of ALX1393 was observed at 15 min after administration, and a significant effect lasted for about 60 min. These antinociceptive effects were reversed completely by strychnine injected immediately after the administration of ALX1393. In the formalin test, ALX1393 inhibited pain behaviors in a dose-dependent manner, both in the early and late phases, although the influence was greater in the late phase. In contrast to antinociceptive action, ALX1393 did not affect motor function up to 40 microg. CONCLUSIONS: This study demonstrates the antinociceptive action of ALX1393 on acute pain. These findings suggest that the inhibitory neurotransmitter transporters are promising targets for the treatment of acute pain and that the selective inhibitor of GlyT2 could be a novel therapeutic drug.
Asunto(s)
Analgésicos/administración & dosificación , Proteínas de Transporte de Glicina en la Membrana Plasmática/antagonistas & inhibidores , Dolor/tratamiento farmacológico , Serina/análogos & derivados , Enfermedad Aguda , Animales , Relación Dosis-Respuesta a Droga , Inyecciones Espinales , Masculino , Dimensión del Dolor , Umbral del Dolor/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Prueba de Desempeño de Rotación con Aceleración Constante , Serina/administración & dosificación , Estricnina/administración & dosificaciónRESUMEN
Alkaptonuric ochronosis, caused by a deficiency of homogentisate 1,2-dioxygenase, is a rare, autosomal recessive, metabolic disorder. Accumulation of homogentisate acid (HGA) at the connective tissue destructs the spine and large joints, and cardiac valvular disease is prominent. In this report, we describe a case of alkaptonuric ochronosis for anesthetic management. A 75-year-old female patient with the disease was scheduled for a total-hip arthroplasty. We avoided applying general anesthesia for her valvular regurgitations. Spinal anesthesia was achieved successfully, and resulted in a hypesthesia level at T12. Although a epidural catheter was indwelled with no leak of cerebrospinal fluid, an accidental dural puncture appeared later during the surgery, suggesting a subdural catheterization. She had an uneventful perioperative course without any symptoms. In the patient of alkaptonuric ochronosis, the dura and arachnoid membrane could be damaged made vulnerable by HGA. In addition, since the clinical findings resemble ankylosing spondylitis, degenerative changes such as a narrowing of the disk space and spine fusion would make the regional technique unsuccessful. In term of anesthesia, alkaptonuric ochronosis requires ingenuity since there are a number of factors associated with prevention of untoward complications. Each case is to be evaluated individually and managed carefully.
Asunto(s)
Alcaptonuria/complicaciones , Anestesia Epidural , Anestesia Raquidea , Artroplastia de Reemplazo de Cadera , Anciano , Anestesia Epidural/efectos adversos , Anestesia General , Contraindicaciones , Femenino , Fracturas del Fémur/complicaciones , Fracturas del Fémur/cirugía , Enfermedades de las Válvulas Cardíacas/etiología , Ácido Homogentísico/metabolismo , Humanos , Artropatías/etiologíaRESUMEN
We compared jugular venous blood oxygen saturation (Sj(O) (2)) and the arterial-to-jugular-bulb venous oxygen content difference (AjD(O) (2)) between bispectral index (BIS) values of 40 and 60, adjusted by the infusion rate of propofol. Eighteen postoperative neurosurgical patients (Glasgow Coma Scale [GCS] scores, 11-15) were enrolled. Normocapnia, normothermia, and a mean arterial blood pressure greater than 70 mmHg were maintained. At BIS values of 40 and 60, hemoglobin, oxygen saturation, and the oxygen partial pressure of arterial and jugular venous blood were measured. Sj(O) (2) at BIS40 (58 +/- 9%) was significantly (P < 0.01) lower than that at BIS60 (63 +/- 10%), and AjD(O) (2) at BIS40 (6.3 +/- 1.5 ml.dl(-1)) was significantly (P < 0.01) higher than that at BIS60 (5.7 +/- 1.5 ml.dl(-1); mean +/- SD). At BIS40, status defined as Sj(O) (2) less than 50% was observed in 3 patients, while this status was observed in 1 patient at BIS60. In conclusion, in patients with postoperative neurosurgical surgery (GCS scores, 11-15), decreases of propofol infusion to adjust the BIS value from 40 to 60 increase the cerebral oxygen balance.
Asunto(s)
Anestésicos Intravenosos/administración & dosificación , Venas Yugulares/metabolismo , Oxígeno/sangre , Propofol/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Encéfalo/metabolismo , Circulación Cerebrovascular , Electroencefalografía , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana EdadRESUMEN
A 75-year-old man had neck sprain by traffic accident. He had headache but not orthostatic at first. He also had dysesthesia and pain of upper limbs, neck pain, and nausea. His symptoms vanished immediately after 10 ml bolus thoracic epidural injection of normal saline for about one hour. Succeeding continuous epidural injection of normal saline (10 ml x h(-1)) made him symptom free until stopping injection. If headache of a patient vanished after epidural normal saline injection, a diagnosis of intracranial hypotension syndrome can be made. This patient became pain free after one trial of cervical epidural blood patch of 12 ml. Quantity of blood to be injected into the cervical epidural space can be decided by flood of injected blood from thoracic epidural vent tapped in advance.
Asunto(s)
Hipotensión Intracraneal/diagnóstico , Cloruro de Sodio/administración & dosificación , Anciano , Parche de Sangre Epidural , Humanos , Inyecciones Epidurales , Hipotensión Intracraneal/terapia , Masculino , Resultado del TratamientoRESUMEN
A 58-year-old woman was scheduled for resection of anterior mediastinal tumor. Prolonged mechanical ventilation was required following surgery because of bilateral diaphragmatic injury. Pleural effusion, atelectasis, and syndrome of vena cava superior were observed during the treatment. BiPAP was useful for respiratory support. The patient was discharged from our hospital nine months after surgery. Oxygen therapy was not necessary in the day time. But the patient required respiratory support with BiPAP at night.
Asunto(s)
Anestesia General/métodos , Diafragma/cirugía , Neoplasias del Mediastino/cirugía , Respiración Artificial/métodos , Femenino , Humanos , Persona de Mediana EdadRESUMEN
BACKGROUND: The effects of different volumes (2.4, 2.6, 2.8 and 3.0 ml) of isobaric 0.5% bupivacaine used for spinal anesthesia were compared in 206 patients scheduled for lower limb surgery. METHODS: The spinal anesthesia was performed with the patients in the lateral position and the isobaric 0.5% bupivacaine was injected intrathecally at the L3-4 interspace. RESULTS: The time to maximum cephalad spread of anesthesia (loss of cold sensation) varied between 25 and 40 min. A significant difference was found in cephalad spread between 2.4 ml group and 3.0 ml group (T11 vs T7), and between 2.6 ml group and 3.0 ml group (T11 vs T7). Severe hypotension did not occur during the study. CONCLUSIONS: Spinal anesthesia with 2.8 ml of isobaric 0.5% bupivacaine proved satisfactory for lower limb surgery.