Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Herpes Zóster/diagnóstico , Huésped Inmunocomprometido , Ciática/inmunología , Infecciones Oportunistas Relacionadas con el SIDA/complicaciones , Infecciones Oportunistas Relacionadas con el SIDA/inmunología , Adulto , Femenino , Herpes Zóster/complicaciones , Herpes Zóster/inmunología , Humanos , Ciática/virologíaRESUMEN
BACKGROUND: Mitochondria play an important role in many cellular and physiologic functions. Mitochondria are dynamic organelles, and their fusion and fission regulate cellular signaling, development, and mitochondrial homeostasis. The most common complaint of human immunodeficiency virus (HIV)-sensory neuropathy is pain on the soles in patients with HIV, but the exact molecular mechanisms of HIV neuropathic pain are not clear. In the present study, we investigated the role of mitochondrial dynamin-related protein 1 (Drp1, a GTPase that mediates mitochondrial fission) in the perineural HIV coat glycoprotein gp120-induced neuropathic pain state. METHODS: Neuropathic pain was induced by the application of recombinant HIV-1 envelope protein gp120 into the sciatic nerve. Mechanical threshold was tested using von Frey filaments. The mechanical threshold response was assessed over time using the area under curves. Intrathecal administration of antisense oligodeoxynucleotide (ODN) against Drp1, mitochondrial division inhibitor-1 (mdivi-1), or phenyl-N-tert-butylnitrone (a reactive oxygen species scavenger) was given. The expression of spinal Drp1 was examined using western blots. The expression of mitochondrial superoxide in the spinal dorsal horn was examined using MitoSox imaging. RESULTS: Intrathecal administration of either antisense ODN against Drp1 or mdivi-1 decreased mechanical allodynia (a sensation of pain evoked by nonpainful stimuli) in the gp120 model. Intrathecal ODN or mdivi-1 did not change basic mechanical threshold in sham surgery rats. Intrathecal Drp1 antisense ODN decreased the spinal expression of increased Drp1 protein induced by peripheral gp120 application. Intrathecal phenyl-N-tert-butylnitrone reduced mechanical allodynia. Furthermore, both intrathecal Drp1 antisense ODN and mdivi-1 reversed the upregulation of mitochondrial superoxide in the spinal dorsal horn in the gp120 neuropathic pain state. CONCLUSIONS: These data suggest that mitochondrial division plays a substantial role in the HIV gp120-related neuropathic pain state through mitochondrial reactive oxygen species and provides evidence for a novel approach to treating chronic pain in patients with HIV.
Asunto(s)
Analgésicos/farmacología , Óxidos N-Cíclicos/farmacología , Dinaminas/metabolismo , Depuradores de Radicales Libres/farmacología , Proteína gp120 de Envoltorio del VIH , Hiperalgesia/prevención & control , Mitocondrias/efectos de los fármacos , Oligonucleótidos Antisentido/metabolismo , Células del Asta Posterior/efectos de los fármacos , Quinazolinonas/farmacología , Ciática/prevención & control , Superóxidos/metabolismo , Analgésicos/administración & dosificación , Animales , Óxidos N-Cíclicos/administración & dosificación , Modelos Animales de Enfermedad , Dinaminas/genética , Depuradores de Radicales Libres/administración & dosificación , Infecciones por VIH/complicaciones , Infecciones por VIH/virología , Hiperalgesia/genética , Hiperalgesia/metabolismo , Hiperalgesia/fisiopatología , Hiperalgesia/virología , Inyecciones Espinales , Masculino , Mitocondrias/metabolismo , Dinámicas Mitocondriales/efectos de los fármacos , Oligonucleótidos Antisentido/administración & dosificación , Oligonucleótidos Antisentido/genética , Umbral del Dolor/efectos de los fármacos , Células del Asta Posterior/metabolismo , Quinazolinonas/administración & dosificación , Ratas Sprague-Dawley , Proteínas Recombinantes , Ciática/genética , Ciática/metabolismo , Ciática/fisiopatología , Ciática/virología , Factores de TiempoRESUMEN
BACKGROUND: Symptom of herpes zoster is sometimes difficult to distinguish from sciatica induced by spinal diseases, including lumbar disc herniation and spinal canal stenosis. Here we report a case of sciatica mimicking lumbar canal stenosis. CASE PRESENTATION: A 74-year-old Chinese male patient visited our hospital for left-sided sciatic pain upon standing or walking for 5 min of approximately 1 month's duration. At the first visit to our hospital, there were no skin lesions. A magnetic resonance imaging showed spinal canal stenosis between the 4th and 5th lumbar spine. Thus, we diagnosed the patient with sciatica induced by spinal canal stenosis. We considered decompression surgery for the stenosis of 4th and 5th lumbar spine because conservative therapy failed to relieve the patient's symptom. At that time, the patient complained of a skin rash involving his left foot for several days. A vesicular rash and erythema were observed on the dorsal and plantar surfaces of the great toe and lateral malleolus. The patient was diagnosed with herpes zoster in the left 5th lumbar spinal nerve area based on clinical findings, including the characteristics of the pain and vesicular rash and erythema in the 5th lumbar spinal dermatome. The patient was treated with famciclovir (1,500 mg/day) and non-steroidal anti-inflammatory drugs. After 1 week of medication, the skin rash resolved and pain relief was obtained. CONCLUSION: In conclusion, spinal surgeons should keep in mind herpes zoster infection as one of the possible differential diagnoses of sciatica, even if there is no typical skin rash.
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2-Aminopurina/análogos & derivados , Antivirales/uso terapéutico , Constricción Patológica/congénito , Herpes Zóster/diagnóstico , Vértebras Lumbares/anomalías , Ciática/diagnóstico , 2-Aminopurina/uso terapéutico , Anciano , Constricción Patológica/diagnóstico , Constricción Patológica/tratamiento farmacológico , Constricción Patológica/fisiopatología , Constricción Patológica/virología , Diagnóstico Diferencial , Famciclovir , Herpes Zóster/tratamiento farmacológico , Herpes Zóster/fisiopatología , Herpes Zóster/virología , Humanos , Vértebras Lumbares/efectos de los fármacos , Vértebras Lumbares/inervación , Vértebras Lumbares/fisiopatología , Vértebras Lumbares/virología , Región Lumbosacra/inervación , Región Lumbosacra/fisiopatología , Región Lumbosacra/virología , Masculino , Ciática/tratamiento farmacológico , Ciática/fisiopatología , Ciática/virología , Resultado del TratamientoRESUMEN
BACKGROUND: Human immunodeficiency virus (HIV)-related painful sensory neuropathies primarily consist of the HIV infection-related distal sensory polyneuropathy and antiretroviral toxic neuropathies. Pharmacotherapy provides only partial relief of pain in patients with HIV/acquired immune deficiency syndrome because little is known about the exact neuropathological mechanisms for HIV-associated neuropathic pain (NP). Hypofunction of γ-aminobutyric acid (GABA) GABAergic inhibitory mechanisms has been reported after peripheral nerve injury. In this study, we tested the hypothesis that HIV gp120 combined with antiretroviral therapy reduces spinal GABAergic inhibitory tone and that restoration of GABAergic inhibitory tone will reduce HIV-related NP in a rat model. METHODS: The application of recombinant HIV-1 envelope protein gp120 into the sciatic nerve plus systemic ddC (one antiretroviral drug) induced mechanical allodynia. The hind paws of rats were inoculated with replication-defective herpes simplex virus (HSV) vectors genetically encoding gad1 gene to express glutamic acid decarboxylase 67 (GAD67), an enzyme that catalyzes the decarboxylation of glutamate to GABA. Mechanical threshold was tested using von Frey filaments before and after treatments with the vectors. The expression of GAD67 in both the lumbar spinal cord and the L4-5 dorsal root ganglia was examined using western blots. The expression of mitochondrial superoxide in the spinal dorsal horn was examined using MitoSox imaging. The immunoreactivity of spinal GABA, pCREB, and pC/EBPß was tested using immunohistochemistry. RESULTS: In the gp120 with ddC-induced neuropathic pain model, GAD67 expression mediated by the HSV vector caused an elevation of mechanical threshold that was apparent on day 3 after vector inoculation. The antiallodynic effect of the single HSV vector inoculation expressing GAD67 lasted >28 days. The area under the time-effect curves in the HSV vector expressing GAD67 was increased compared with that in the control vectors (P = 0.0005). Intrathecal GABA-A/B agonists elevated mechanical threshold in the pain model. The HSV vectors expressing GAD67 reversed the lowered GABA immunoreactivity in the spinal dorsal horn in the neuropathic rats. HSV vectors expressing GAD67 in the neuropathic rats reversed the increased signals of mitochondrial superoxide in the spinal dorsal horn. The vectors expressing GAD67 reversed the upregulated immunoreactivity expression of pCREB and pC/EBPß in the spinal dorsal horn in rats exhibiting NP. CONCLUSIONS: Based on our results, we suggest that GAD67 mediated by HSV vectors acting through the suppression of mitochondrial reactive oxygen species and transcriptional factors in the spinal cord decreases pain in the HIV-related neuropathic pain model, providing preclinical evidence for gene therapy applications in patients with HIV-related pain states.
Asunto(s)
Técnicas de Transferencia de Gen , Terapia Genética/métodos , Vectores Genéticos , Glutamato Descarboxilasa/genética , Proteína gp120 de Envoltorio del VIH/metabolismo , Infecciones por VIH/complicaciones , Nervio Ciático/enzimología , Ciática/terapia , Simplexvirus/genética , Zalcitabina , Animales , Proteína beta Potenciadora de Unión a CCAAT/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Descarboxilación , Modelos Animales de Enfermedad , Glutamato Descarboxilasa/biosíntesis , Ácido Glutámico/metabolismo , Proteína gp120 de Envoltorio del VIH/genética , Infecciones por VIH/genética , Infecciones por VIH/metabolismo , Infecciones por VIH/virología , Humanos , Masculino , Mitocondrias/metabolismo , Umbral del Dolor , Fosforilación , Ratas Sprague-Dawley , Nervio Ciático/fisiopatología , Nervio Ciático/virología , Ciática/enzimología , Ciática/genética , Ciática/fisiopatología , Ciática/virología , Simplexvirus/enzimología , Asta Dorsal de la Médula Espinal/metabolismo , Superóxidos/metabolismo , Factores de Tiempo , Ácido gamma-Aminobutírico/metabolismoRESUMEN
The herpes zoster virus is a rare but potential cause of acute motor weakness. This article describes 2 patients with drop foot secondary to an infection of varicella zoster who were incorrectly referred to an orthopedic clinic from their general practitioners. The first patient was a 74-year-old man who presented with weakness in the right foot and a vesicular rash. The pattern of disease supported the clinical diagnosis of shingles affecting the L5 motor and sensory division. No investigation was required, and the patient was treated with a foot drop splint. The second patient was a 71-year-old man who presented with right leg and foot weakness and a vesicular rash affecting his right buttock and posterior right thigh. Lumbar magnetic resonance excluded a stenotic lesion; electrophysiological studies supported the diagnosis of a lower motor neuron lesion. The patient was treated with a 1-week course of acyclovir and a foot drop splint. The correct diagnosis will aid in correct referral and will prompt management, which will potentially provide a faster and better outcome for the patient.
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Aciclovir/uso terapéutico , Antivirales/uso terapéutico , Trastornos Neurológicos de la Marcha/virología , Herpes Zóster/complicaciones , Ciática/virología , Anciano , Electrofisiología , Exantema/diagnóstico , Exantema/tratamiento farmacológico , Exantema/virología , Trastornos Neurológicos de la Marcha/diagnóstico , Trastornos Neurológicos de la Marcha/terapia , Herpes Zóster/diagnóstico , Herpes Zóster/tratamiento farmacológico , Herpesvirus Humano 3/efectos de los fármacos , Herpesvirus Humano 3/fisiología , Humanos , Imagen por Resonancia Magnética , Masculino , Debilidad Muscular/diagnóstico , Debilidad Muscular/terapia , Debilidad Muscular/virología , Ciática/diagnóstico , Ciática/terapia , Férulas (Fijadores) , Resultado del TratamientoRESUMEN
Herpes zoster is a disease which occurs secondary to the reactivation of varicella-zoster virus. Motor involvement in acute herpes zoster is rare. We report a case of sciatica L5 due to herpes zoster infection with motor loss. Typical skin lesions occurred one week before the sciatica. Radiological finding did not explain the paresis. The diagnosis of zoster sciatica with motor involvement was suspected. Serological tests and cerebrospinal fluid examination established the diagnosis. The antiviral and physical treatment was conducted in order to improve functional outcome.
Asunto(s)
Antivirales/uso terapéutico , Ataxia/tratamiento farmacológico , Herpes Zóster/complicaciones , Neuroborreliosis de Lyme/diagnóstico , Neuroborreliosis de Lyme/tratamiento farmacológico , Meningomielocele/virología , Ciática/etiología , Anciano , Electromiografía , Femenino , Herpesvirus Humano 3/genética , Herpesvirus Humano 3/aislamiento & purificación , Humanos , Neuroborreliosis de Lyme/patología , Imagen por Resonancia Magnética , Meningomielocele/diagnóstico , Meningomielocele/tratamiento farmacológico , Reacción en Cadena de la Polimerasa , Ciática/virología , Enfermedades de la Piel/etiología , Enfermedades de la Piel/virología , Médula Espinal/patologíaRESUMEN
We evaluated the prevalence of hepatitis C virus (HCV) infection in Italian patients suffering from fibromyalgia (FM), in comparison with patients affected by non-HCV related rheumatic degenerative disorders. Consecutive patients with FM and a statistically comparable group of patients suffering from peripheral osteoarthritis (OA) or sciatica due to L4-L5 or L5-S1 herniated disc were tested for HCV infection with a third-generation microparticle enzyme immunoassay (MEIA). In the positive cases, a third-generation recombinant immunoblot assay (RIBA) confirmatory test and serum HCV-RNA test were performed. Fisher's exact test was performed to compare the prevalence of HCV infection (MEIA- and RIBA-positive results) obtained in the two enrolled groups. Enrolled were 152 subjects suffering from FM and 152 patients with peripheral OA or sciatica. Anti-HCV antibodies were found in 7/152 (4.6%) patients suffering from FM and in 5/152 (3.3%) of control subjects. No statistically significant differences in HCV prevalence were detected between cases and controls. Our present report does not confirm previous data indicating an increased prevalence of HCV in FM patients and does not seem to support a significant pathogenetic role of HCV under this condition.
Asunto(s)
Instituciones de Atención Ambulatoria , Fibromialgia/epidemiología , Hepacivirus/aislamiento & purificación , Hepatitis C/epidemiología , Pacientes Ambulatorios , Adulto , Anciano , Anciano de 80 o más Años , Comorbilidad , Femenino , Fibromialgia/diagnóstico , Fibromialgia/virología , Hepacivirus/inmunología , Hepatitis C/diagnóstico , Hepatitis C/virología , Humanos , Immunoblotting , Técnicas para Inmunoenzimas , Desplazamiento del Disco Intervertebral/epidemiología , Desplazamiento del Disco Intervertebral/virología , Italia/epidemiología , Masculino , Persona de Mediana Edad , Osteoartritis/epidemiología , Osteoartritis/virología , Prevalencia , Estudios Prospectivos , Ciática/epidemiología , Ciática/virologíaRESUMEN
OBJECTIVE: To evaluate the prevalence of hepatitis C virus (HCV) infection in patients with psoriatic arthritis (PsA), compared with patients affected by non HCV-related rheumatic degenerative disorders. METHODS: One-hundred consecutive subjects with PsA, and a statistically comparable group of 100 consecutive patients with peripheral osteoarthritis (OA) or sciatica due to L4-L5 or L5-S1 herniated disc were tested for HCV infection with a third-generation microparticle enzyme immunoassay (MEIA). Positive cases were submitted to a third-generation recombinant immunoblot assay (RIBA) confirmatory test. Comparison between the HCV prevalence obtained in the 2 enrolled groups was performed using Fisher's exact test. RESULTS: Anti-HCV antibodies were found with the MEIA method, in 1 patient with PsA, and in 4 patients with OA or sciatica. The RIBA method confirmed MEIA results in all positive patients. The difference in HCV prevalence detected in the PsA group and in the control group was not statistically significant (P = 0.68). Furthermore, HCV prevalence in PsA patients was lower than the ones reported in different geographic areas of Italy. CONCLUSION: Our present report does not confirm previous data that indicated an increased prevalence of HCV in PsA patients, and as a consequence, does not sustain a possible trigger role of HCV in cases of PsA. The absence of clinical or instrumental resources that consent a definite differential diagnosis between PsA and HCV-related arthritis was outlined and analyzed.
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Artritis Psoriásica/epidemiología , Artritis Psoriásica/virología , Hepacivirus/aislamiento & purificación , Hepatitis C/complicaciones , Hepatitis C/epidemiología , Artritis Psoriásica/inmunología , Hepacivirus/inmunología , Hepatitis C/inmunología , Humanos , Desplazamiento del Disco Intervertebral/epidemiología , Desplazamiento del Disco Intervertebral/inmunología , Desplazamiento del Disco Intervertebral/virología , Italia/epidemiología , Osteoartritis/epidemiología , Osteoartritis/inmunología , Osteoartritis/virología , Prevalencia , Ciática/epidemiología , Ciática/inmunología , Ciática/virologíaRESUMEN
We report three cases of herpes zoster sciatica with motor loss preceding the typical skin lesions. Serological tests and cerebrospinal fluid examination established the diagnosis. Two patients had residual motor loss after 1 and 3 months, respectively. Immunodepression and other risk factors should be looked for routinely. Early diagnosis and treatment may improve the prognosis. Tests for antibodies or viral DNA in cerebrospinal fluid can be helpful, although negative results do not rule out the diagnosis.