RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Fermented milk and palm wine are regularly used by several ethnic groups in Cameroon in traditional treatment rituals for infections, inflammatory, cardiovascular disorders, and even metabolic diseases such as diabetes, hypercholesterolemia etc. Reports from many studies have demonstrated that fermented milk and palm wine are potential sources of probiotic bacteria. However, the capacity of probiotics isolated from these natural sources to alleviate neuropathic pain has not been experimentally tested. AIM OF THE STUDY: This study aimed at investigating the ameliorative potential of lactic acid bacteria isolated from palm wine and traditional fermented cow milk on the chronic constriction injury (CCI) induced neuropathic pain in mice. MATERIALS AND METHODS: Pour plating technique on De Man Rogasa (MRS) agar was utilised for isolation of lactic acid bacteria from fermented cow milk and palm wine, and identified using the 16S r RNA gene sequencing. Neuropathic pain was induced by chronic constriction injury of the sciatic nerve. These bacteria were orally administered at different concentrations to Balb/c mice by gavage for 14 consecutive days. Cold allodynia, mechanical hyperalgesia and exploratory behaviour were evaluated on day 0, 7th and 14th respectively. The total level of calcium, oxidative stress markers and myeloperoxidase were also quantified in the sciatic nerve homogenate. Cyclooxygenase-2(COX-2) and cytokine profile were determined from serum. RESULTS: Lactic acid bacteria were isolated from fermented cow milk and palm wine and two isolates were chosen according to their probiotic potentials and identified as strain of Limolactobacillus fermentum and Enterococcus lactis. Their 16 S rRNA gene sequences were deposited in NCBI genbank with accession number of OP896078 and OR619545, respectively. Pretreatment with Limosilactobacillus fermentum and Enterococcus lactis significantly alleviated mechanical hyperalgesia and cold allodynia with similar effect to the reference drug, morphine. These two isolates ameliorated CCI induced neuropathic pain by increasing antioxida776nts (GSH, CAT and SOD, P < 0.01) and decreasing pro-oxidants (MDA and NO, P < 0.01). Also, they inhibited the release of proinflammatory cytokines (IL-1ß, TNF-α, IFN-γ, and IL-6; P < 0.01) and IL-10 level was significantly (P < 0.01) increased when compared to the negative control. Treatment with these bacteria significantly dropped the level of total calcium (P < 0.01), COX-2 (P < 0.01) and MPO (P < 0.01) when compared with the negative control. CONCLUSION: The neuroprotective potentials of these selected lactic acid bacteria against CCI induced neuropathic pain may be attributed to their anti-oxidant, anti-inflammatory properties and reduced calcium deposition in sciatic nerve.
Assuntos
Limosilactobacillus fermentum , Camundongos Endogâmicos BALB C , Neuralgia , Probióticos , Animais , Probióticos/farmacologia , Neuralgia/tratamento farmacológico , Neuralgia/microbiologia , Masculino , Camundongos , Camarões , Hiperalgesia/tratamento farmacológico , Produtos Fermentados do Leite/microbiologia , Citocinas/metabolismo , Enterococcus , Leite/microbiologia , Modelos Animais de DoençasRESUMO
BACKGROUND: Existing evidence suggests that the composition of the gut microbiota is associated with neuropathic pain (NP), but the mechanistic link is elusive. Peroxisome proliferator-activated receptor α (PPARα) has been shown to be a pharmacological target for the treatment of metabolic disorders, and its expression is also involved in inflammatory regulation. The aim of this study was to investigate the important modulatory effects of PPARα on gut microbiota and spinal cord metabolites in mice subjected to chronic constriction injury. METHODS: We analyzed fecal microbiota and spinal cord metabolic alterations in mice from the sham, CCI, GW7647 (PPARα agonist) and GW6471 (PPARα antagonist) groups by 16â¯S rRNA amplicon sequencing and untargeted metabolomics analysis. On this basis, the intestinal microbiota and metabolites that were significantly altered between treatment groups were analyzed in a combined multiomics analysis. We also investigated the effect of PPARα on the polarization fractionation of spinal microglia. RESULTS: PPARα agonist significantly reduce paw withdrawal threshold and paw withdrawal thermal latency, while PPARα antagonist significantly increase paw withdrawal threshold and paw withdrawal thermal latency. 16â¯S rRNA gene sequencing showed that intraperitoneal injection of GW7647 or GW6471 significantly altered the abundance, homogeneity and composition of the gut microbiome. Analysis of the spinal cord metabolome showed that the levels of spinal cord metabolites were shifted after exposure to GW7647 or GW6471. Alterations in the composition of gut microbiota were significantly associated with the abundance of various spinal cord metabolites. The abundance of Licheniformes showed a significant positive correlation with nicotinamide, benzimidazole, eicosanoids, and pyridine abundance. Immunofluorescence results showed that intraperitoneal injection of GW7647 or GW6471 altered microglial activation and polarization levels. CONCLUSION: Our study shows that PPARα can promote M2-type microglia polarization, as well as alter gut microbiota and metabolites in CCI mice. This study enhances our understanding of the mechanism of PPARα in the treatment of neuropathic pain.
Assuntos
Microbioma Gastrointestinal , Metabolômica , Neuralgia , PPAR alfa , RNA Ribossômico 16S , Medula Espinal , Animais , Masculino , Camundongos , Fezes/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Microglia/efeitos dos fármacos , Neuralgia/metabolismo , Neuralgia/tratamento farmacológico , Neuralgia/microbiologia , Oxazóis , PPAR alfa/metabolismo , RNA Ribossômico 16S/genética , Medula Espinal/metabolismo , Medula Espinal/efeitos dos fármacos , Tirosina/análogos & derivadosRESUMO
The aim of this study was to explore the relationships among gut microbiota disturbances and serum and spinal cord metabolic disorders in neuropathic pain. 16S rDNA amplicon sequencing and serum and spinal cord metabolomics were used to identify alterations in the microbiota and metabolite profiles in the sham rats and the chronic constriction injury (CCI) model rats. Correlations between the abundances of gut microbiota components at the genus level, the levels of serum metabolites, and pain-related behavioural parameters were analysed. Ingenuity pathway analysis (IPA) was applied to analyse the interaction networks of the differentially expressed serum metabolites. First, we found that the composition of the gut microbiota was different between rats with CCI-induced neuropathic pain and sham controls. At the genus level, the abundances of Helicobacter, Phascolarctobacterium, Christensenella, Blautia, Streptococcus, Rothia and Lactobacillus were significantly increased, whereas the abundances of Ignatzschineria, Butyricimonas, Escherichia, AF12, and Corynebacterium were significantly decreased. Additionally, 72 significantly differentially expressed serum metabolites and 17 significantly differentially expressed spinal cord metabolites were identified between the CCI rats and the sham rats. Finally, correlation analysis showed that changes in the gut microbiota was significantly correlated with changes in serum metabolite levels, suggesting that dysbiosis of the gut microbiota is an important factor in modulating metabolic disturbances in the context of neuropathic pain. In conclusion, our research provides a novel perspective on the potential roles of the gut microbiota and related metabolites in neuropathic pain.
Assuntos
Bactérias/isolamento & purificação , Microbioma Gastrointestinal , Neuralgia/metabolismo , Neuralgia/microbiologia , Animais , Bactérias/classificação , Carga Bacteriana , Biomarcadores/sangue , Hiperalgesia/etiologia , Ligadura , Masculino , Redes e Vias Metabólicas , Neuralgia/etiologia , Limiar da Dor , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Ribotipagem , Neuropatia Ciática/complicações , Medula Espinal/metabolismoRESUMO
BACKGROUND: Neuropathic pain is an abnormally increased sensitivity to pain, especially from mechanical or thermal stimuli. To date, the current pharmacological treatments for neuropathic pain are still unsatisfactory. The gut microbiota reportedly plays important roles in inducing neuropathic pain, so probiotics have also been used to treat it. However, the underlying questions around the interactions in and stability of the gut microbiota in a spared nerve injury-induced neuropathic pain model and the key microbes (i.e., the microbes that play critical roles) involved have not been answered. We collected 66 fecal samples over 2 weeks (three mice and 11 time points in spared nerve injury-induced neuropathic pain and Sham groups). The 16S rRNA gene was polymerase chain reaction amplified, sequenced on a MiSeq platform, and analyzed using a MOTHUR- UPARSE pipeline. RESULTS: Here we show that spared nerve injury-induced neuropathic pain alters gut microbial diversity in mice. We successfully constructed reliable microbial interaction networks using the Metagenomic Microbial Interaction Simulator (MetaMIS) and analyzed these networks based on 177,147 simulations. Interestingly, at a higher resolution, our results showed that spared nerve injury-induced neuropathic pain altered both the stability of the microbial community and the key microbes in a gut micro-ecosystem. Oscillospira, which was classified as a low-abundance and core microbe, was identified as the key microbe in the Sham group, whereas Staphylococcus, classified as a rare and non-core microbe, was identified as the key microbe in the spared nerve injury-induced neuropathic pain group. CONCLUSIONS: In summary, our results provide novel experimental evidence that spared nerve injury-induced neuropathic pain reshapes gut microbial diversity, and alters the stability and key microbes in the gut.
Assuntos
DNA Bacteriano/genética , Microbioma Gastrointestinal/genética , Metagenoma , Interações Microbianas/genética , Neuralgia/microbiologia , Animais , Clostridiales/genética , Clostridiales/isolamento & purificação , Modelos Animais de Doenças , Fezes/microbiologia , Feminino , Variação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Lactobacillaceae/genética , Lactobacillaceae/isolamento & purificação , Camundongos , Camundongos Endogâmicos C57BL , Neuralgia/fisiopatologia , Nervo Fibular/lesões , RNA Ribossômico 16S/genética , Staphylococcus/genética , Staphylococcus/isolamento & purificação , Nervo Sural/lesõesRESUMO
Neuropathic pain (NP) is a sustained and nonreversible condition characterized by long-term devastating physical and psychological damage. Therefore, it is urgent to identify an effective treatment for NP. Unfortunately, the precise pathogenesis of NP has not been elucidated. Currently, the microbiota-gut-brain axis has drawn increasing attention, and the emerging role of gut microbiota is investigated in numerous diseases including NP. Gut microbiota is considered as a pivotal regulator in immune, neural, endocrine, and metabolic signaling pathways, which participates in forming a complex network to affect the development of NP directly or indirectly. In this review, we conclude the current understanding of preclinical and clinical findings regarding the role of gut microbiota in NP and provide a novel therapeutic method for pain relief by medication and dietary interventions.
Assuntos
Microbioma Gastrointestinal , Neuralgia/microbiologia , Neuralgia/fisiopatologia , Encéfalo , Humanos , Manejo da DorRESUMO
Leprosy, which is caused by the human pathogen Mycobacterium leprae, causes nerve damage, deformity and disability in over 200,000 people every year. Because of the long doubling time of M. leprae (13 days) and the delayed onset of detectable symptoms, which is estimated to be approximately 3-7 years after infection, there is always a large percentage of subclinically infected individuals in the population who will eventually develop the disease, mainly in endemic countries. piRNAs comprise the largest group of small noncoding RNAs found in humans, and they are distinct from microRNAs (miRNAs) and small interfering RNAs (siRNAs). piRNAs function in transposon silencing, epigenetic regulation, and germline development. The functional role of piRNAs and their associated PIWI proteins have started to emerge in the development of human cancers and viral infections, but their relevance to bacterial diseases has not been investigated. The present study reports the piRNome of human skin, revealing that all but one of the piRNAs examined are downregulated in leprosy skin lesions. Considering that one of the best characterized functions of piRNAs in humans is posttranscriptional mRNA silencing, their functions are similar to what we have described for miRNAs, including acting on apoptosis, M. leprae recognition and engulfment, Schwann cell (SC) demyelination, epithelial-mesenchymal transition (EMT), loss of sensation and neuropathic pain. In addition to new findings on leprosy physiopathology, the discovery of relevant piRNAs involved in disease processes in human skin may provide new clues for therapeutic targets, specifically to control nerve damage, a prominent feature of leprosy that has no currently available pharmaceutical treatment.
Assuntos
Transição Epitelial-Mesenquimal , Hanseníase/genética , Hanseníase/patologia , Mycobacterium leprae/patogenicidade , Neuralgia/patologia , RNA Interferente Pequeno/genética , Células de Schwann/patologia , Estudos de Casos e Controles , Doenças Desmielinizantes , Epigênese Genética , Humanos , Hanseníase/microbiologia , Neuralgia/metabolismo , Neuralgia/microbiologia , Células de Schwann/metabolismo , Células de Schwann/microbiologiaAssuntos
Hidradenite Supurativa/complicações , Neuralgia/epidemiologia , Qualidade de Vida , Feminino , Finlândia/epidemiologia , Hidradenite Supurativa/psicologia , Humanos , Masculino , Neuralgia/diagnóstico , Neuralgia/etiologia , Neuralgia/microbiologia , Medição da Dor , Testes Psicológicos/estatística & dados numéricos , Estudos Retrospectivos , Autorrelato/estatística & dados numéricos , Índice de Gravidade de DoençaRESUMO
Patients with chronic neuropathic pain frequently suffer from symptoms of anhedonia, which is a core symptom of depression. Accumulating studies suggest that gut microbiota may play a role in depression via gut-microbiota-brain axis. However, it is unknown whether gut microbiota plays a role in neuropathic pain-associated anhedonia. Here, we used a rat model of spared nerve injury (SNI). Hierarchical cluster analysis of sucrose preference test (SPT) results was used to classify the SNI rats with or without anhedonia-like phenotype. The 16S ribosomal RNA sequencing analysis showed abnormal composition of gut microbiota in the anhedonia susceptible compared to sham-operated rats and resilient rats. Furthermore, antibiotics-treated mice showed pain as well as depression-like and anhedonia-like phenotypes, suggesting a role of gut microbiota in these abnormal behaviors. Transplantation of fecal microbiota from anhedonia susceptible rats into antibiotics-treated pseudo-germ-free mice significantly exaggerated pain and depression-like phenotypes, including anhedonia. In contrast, transplantation of fecal microbiota from resilient rats into antibiotics-treated pseudo-germ-free mice significantly improved pain and depression-like phenotypes, including anhedonia. In conclusion, this study suggests that abnormal composition of gut microbiota may contribute to anhedonia susceptibility post SNI surgery, and that gut microbiota also plays a role in the pain as well as depression-like phenotypes. Interestingly, fecal microbiota transplantation from SNI rats with or without anhedonia can alter pain, depression-like and anhedonia-like phenotypes in the pseudo-germ-free mice. Therefore, it is likely that gut microbiota plays a key role in the pain as well as depression-like phenotypes including anhedonia in rodents with neuropathic pain.
Assuntos
Anedonia/fisiologia , Depressão/microbiologia , Microbioma Gastrointestinal , Neuralgia/microbiologia , Neuralgia/psicologia , Animais , Comportamento Animal , Depressão/complicações , Modelos Animais de Doenças , Masculino , Camundongos Endogâmicos C57BL , Neuralgia/complicações , Fenótipo , Ratos Sprague-Dawley , Nervo Isquiático/lesõesRESUMO
The chronic aspects of leprosy are discussed here. They are a consequence of the peripheral nerve damage that affects many patients during their lifetime with leprosy. The peripheral nerve damage leaves people unable to feel and with weakness in their hands and feet. They are at risk of damaging their hands and feet, causing the disabilities and deformities that characterise late leprosy. More than 200 000 new leprosy patients are diagnosed globally each year. Better data are needed from cohort studies to estimate the number of patients developing nerve damage and modelling studies are needed to estimate the number of patients who develop disabilities. For some of them, this will be a lifelong disability. Nerve damage is caused by inflammation in leprosy-affected nerves. Patients with nerve damage of <6-mo duration need treatment with steroids. About 66% of multibacillary patients will develop nerve damage. Plastic graded monofilaments can be used to detect nerve damage in leprosy and diabetic clinics. Assessing nerve damage and treating patients with steroids in leprosy programmes needs to be strengthened. The World Health Organization has a successful programme for supplying antibiotics for treating leprosy infection to national leprosy programmes. They should take responsibility for providing steroids to national programmes since this is a core part of the treatment for >66% of multibacillary patients. Patients need to be asked about neuropathic pain symptoms and treated if necessary. Treated leprosy patients are at risk of developing ulcers in their feet. Treatment and prevention needs to be improved through health education, providing protective footwear and patient empowerment.
Assuntos
Hanseníase/complicações , Doenças Negligenciadas/complicações , Doença Crônica , Avaliação da Deficiência , Eritema Nodoso/microbiologia , Humanos , Hanseníase/diagnóstico , Hanseníase/economia , Doenças Negligenciadas/diagnóstico , Doenças Negligenciadas/economia , Doenças do Sistema Nervoso/microbiologia , Neuralgia/microbiologia , Transtornos de Sensação/microbiologia , Estigma SocialAssuntos
Edema/microbiologia , Hanseníase Dimorfa/diagnóstico , Hanseníase Dimorfa/tratamento farmacológico , Hanseníase Multibacilar/diagnóstico , Hanseníase Multibacilar/tratamento farmacológico , Idoso , Anti-Inflamatórios/uso terapêutico , Quimioterapia Combinada , Eritema/microbiologia , Feminino , Humanos , Hansenostáticos/uso terapêutico , Hanseníase Dimorfa/complicações , Hanseníase Multibacilar/complicações , Neuralgia/microbiologia , Parestesia/microbiologia , Prednisolona/uso terapêutico , Prurido/microbiologiaRESUMO
BACKGROUND: Type 2 lepra reaction (T2R) is a difficult-to-manage condition in leprosy, and an effective and safe steroid-sparing agent is needed for its management. The World Health Organization proposes clofazimine and recommends pentoxifylline for T2R. Our study was done to compare the effectiveness and safety of clofazimine and pentoxifylline therapy in patients with T2R. METHODS: Twenty patients with T2R were randomized equally. Group A received pentoxifylline 400 mg t.d.s, group B received clofazimine 100 mg t.d.s. for 12 weeks. Both groups received prednisolone 40 mg o.d., tapered over 12 weeks. The effectiveness parameters were days needed for resolution of cutaneous and systemic manifestations, relapses, cutaneous score, systemic score, and average daily prednisolone intake. Safety parameters were spontaneously appearing adverse events and laboratory parameter changes. RESULTS: The cutaneous scores in the clofazimine (P < 0.001) and pentoxifylline groups (P < 0.001) showed a progressive decline in subsequent follow-ups. Individual follow-ups were significantly lower than baseline in both groups (P < 0.05). Systemic scores fared similarly. There were no significant intergroup changes. Average daily prednisolone intake progressively decreased in group B (P < 0.001). Cutaneous and systemic manifestations took a comparable time to resolve. Both drugs were safe. CONCLUSION: Pentoxifylline effectively reduces initial severity; clofazimine provides sustained improvement but acts slowly.
Assuntos
Artrite Reativa/microbiologia , Clofazimina/uso terapêutico , Hansenostáticos/uso terapêutico , Hanseníase/tratamento farmacológico , Pentoxifilina/uso terapêutico , Inibidores de Fosfodiesterase/uso terapêutico , Adulto , Clofazimina/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Inflamação/microbiologia , Hansenostáticos/efeitos adversos , Hanseníase/complicações , Masculino , Pessoa de Meia-Idade , Neuralgia/microbiologia , Pentoxifilina/efeitos adversos , Inibidores de Fosfodiesterase/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
The aim of this study was to determine the prevalence of neuropathic pain, now recognized as another late complication of leprosy, and its characteristics among leprosy patients. A cross-sectional study was carried out of people treated for leprosy up to at least 5 years ago in a rural area of Ethiopia. Seventy-four patients were interviewed using the Neuropathic Pain Symptom Inventory (NPSI) questionnaire. In total, 78.9% of the patients were female with a mean age of 42.9. The mean time from initial diagnosis to the time of the study was 28.0 years, and 73.0% of patients were diagnosed over 20 years ago. Fifty-two (70.3%) reported having symptoms suggestive of neuropathic pain and the majority described the pain as burning (88.5%), electric (80.8%), stabbing (76.9%), cutting (76.9%), tingling (65.4%), squeezing (57.7%), and/or pressure (53.8%). The pain caused a severe or moderate impact on daily life in 75% and 57.7% of cases, respectively, and 92.3% suffered from disrupted sleep. Eighty percent of patients with pain (42/52) took some medication for pain relief. Neuropathic pain is common in patients treated for leprosy and in more than half of them, it causes disruption in their daily life and sleep, limiting their quality of life even more.
Assuntos
Hanseníase/complicações , Neuralgia/epidemiologia , Neuralgia/fisiopatologia , Qualidade de Vida , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Avaliação da Deficiência , Etiópia/epidemiologia , Feminino , Humanos , Hanseníase/fisiopatologia , Masculino , Pessoa de Meia-Idade , Neuralgia/complicações , Neuralgia/microbiologia , Prevalência , População Rural , Privação do Sono/etiologia , Inquéritos e QuestionáriosAssuntos
Dor Aguda/microbiologia , Dor Crônica/microbiologia , Doença de Lyme/complicações , Dor Musculoesquelética/microbiologia , Neuralgia/microbiologia , Dor Aguda/fisiopatologia , Borrelia burgdorferi , Dor Crônica/fisiopatologia , Humanos , Doença de Lyme/fisiopatologia , Dor Musculoesquelética/fisiopatologia , Neuralgia/fisiopatologiaAssuntos
Infecções por Escherichia coli/complicações , Nervo Femoral , Nefropatias/complicações , Neuralgia/microbiologia , Abscesso do Psoas/complicações , Antibacterianos/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Drenagem , Infecções por Escherichia coli/diagnóstico , Infecções por Escherichia coli/terapia , Feminino , Humanos , Nefropatias/diagnóstico , Nefropatias/microbiologia , Nefropatias/terapia , Pessoa de Meia-Idade , Neuralgia/diagnóstico , Neuralgia/terapia , Abscesso do Psoas/diagnóstico , Abscesso do Psoas/microbiologia , Abscesso do Psoas/terapia , Resultado do TratamentoRESUMO
Tactile allodynia is a common, troublesome feature of neuropathic pain. Allodynia has been proposed to involve abnormal Abeta-afferent coupling in the dorsal horn resulting in C-fibre activation and increased skin blood flow (SBF). Thus, changes in SBF could provide an objective measure of allodynia. We searched for this mechanism in patients with postherpetic neuralgia (PHN) with varying degrees of cutaneous sensory loss. We mapped the allodynic area in PHN patients using cotton buds and von Frey hairs. Quantitative thermal testing was performed to assess small fibre function in the affected and mirror-image areas. At a subsequent visit the area of allodynia was remapped. Then the SBF in the affected and control areas was quantified before and after allodynic stimulation using laser Doppler imaging and subsequent single point continuous monitoring to detect rapid changes. We enrolled 10 PHN patients (medians: age 77 yrs, duration 20 months, ongoing pain 5). The allodynic area (range 11-546 cm2) was stable across the sessions. Thermal testing showed similar (n=5) or reduced (n=5) warmth and pain sensation in the affected versus control area. Following allodynic stimulation (median evoked pain-5) we saw no changes in SBF using either imaging (repeated measures ANOVA, P=0.73) or single point monitoring. This was the case for all patients regardless of the degree of sensory impairment in the affected dermatome. In conclusion, in a representative population of PHN patients we found no evidence of changes in SBF in response to allodynic stimulation. Hence, SBF measurements are not suitable for assessing allodynia.
Assuntos
Herpes Zoster/fisiopatologia , Hiperestesia/fisiopatologia , Neuralgia/fisiopatologia , Limiar da Dor/fisiologia , Pele/irrigação sanguínea , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuralgia/microbiologia , Medição da Dor/métodos , Fluxo Sanguíneo Regional , Pele/fisiopatologia , Fatores de TempoRESUMO
Herpes zoster (HZ) is a common skin disease due to a virus identical to that responsible for chickenpox. In a variable number of cases neuritic pain persist after cutaneous healing. Aim of this investigation was to analyze zoster clinical evolution in 102 immunocompetent patients, subdivided by age (< 60 years and > or = 60 years) and sex, after treatment with acyclovir (4 g/die x 10 days). Signs and symptoms of the disease were evaluated, with particular attention to pain and the duration of post-herpetic neuralgia. Vescicular eruption was most frequently found in the thoraco-abdominal region and in the trigeminal one, with no significant differences among the subgroups. Two thirds of the subjects complained of pain and it was prevalent in female sex (84% of cases vs 53%, p < 0.01) but not in any age-class. After 1 months from the episode (and its pharmacological treatment), post-herpetic neuralgia was still present in about 20% of the patients, above all in those > or = 60 years; this last difference reached statistical significance after 6 months (9.7% vs 1.4% for subjects > or = 60 years and < 60 years respectively, p < 0.05). No patient showed any adverse pharmacological effect after treatment. We conclude that acyclovir is well accepted both in young and elderly immune-competent subjects suffering from HZ, but it necessitates further efficacy investigations in sight of its broader utilization.
Assuntos
Aciclovir/uso terapêutico , Herpes Zoster/complicações , Neuralgia/microbiologia , Neuralgia/prevenção & controle , Fatores Etários , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Treatment of the pain of acute herpes zoster by local anesthetic injections has drawbacks. Topical percutaneous local anesthesia (TPLA) may offer another strategy of providing regional analgesia in affected patients. OBJECTIVE: We evaluate the analgesic efficacy and safety of 9% (wt/vol) lidocaine (base) in petrolatum/paraffin ointment in patients with acute herpes zoster. METHODS: Ointment was applied to the affected skin of 22 patients. Pain, tenderness, sensitivity to pinprick and cold, and blood lidocaine concentration were measured repeatedly during a 20-hour interval and intermittently thereafter. RESULTS: Mean pain, tenderness, and cutaneous sensation scores were reduced at measurements taken from 4 to 20 hours after ointment application (p < 0.05), but not every patient obtained relief. No patient had local skin irritation or systemic toxic effects related to the local anesthetic. CONCLUSIONS: TPLA is a promising therapy for control of cutaneous pain of acute herpes zoster. Controlled studies should be performed to prove efficacy, determine optimal TPLA formulation, and define dosage limits.
Assuntos
Herpes Zoster/tratamento farmacológico , Lidocaína/uso terapêutico , Dermatopatias Virais/tratamento farmacológico , Doença Aguda , Administração Cutânea , Adulto , Avaliação de Medicamentos , Feminino , Herpes Zoster/patologia , Herpes Zoster/fisiopatologia , Humanos , Lidocaína/administração & dosagem , Lidocaína/efeitos adversos , Lidocaína/sangue , Masculino , Neuralgia/tratamento farmacológico , Neuralgia/microbiologia , Curativos Oclusivos , Pomadas , Dor , Limiar da Dor/efeitos dos fármacos , Parafina , Vaselina , Segurança , Sensação/efeitos dos fármacos , Dermatopatias Virais/patologia , Dermatopatias Virais/fisiopatologiaRESUMO
Herpes zoster is an infection caused by reactivation of dormant varicella-zoster virus. The acute course of herpes zoster is generally benign; however, some patients will experience postherpetic neuralgia characterized by severe, relentless, and at times disabling pain that is often refractory to treatment. While herpes zoster responds to acyclovir, cost-benefit considerations limit the drug's usefulness to only a select group. Postherpetic neuralgia requires a holistic approach, including pharmacologic therapy using several different classes of drugs.
Assuntos
Algoritmos , Herpes Zoster/complicações , Herpes Zoster/tratamento farmacológico , Neuralgia/tratamento farmacológico , Neuralgia/microbiologia , Aciclovir/economia , Aciclovir/uso terapêutico , Corticosteroides/uso terapêutico , Analgésicos/uso terapêutico , Anticonvulsivantes/uso terapêutico , Antidepressivos Tricíclicos/uso terapêutico , Antipsicóticos/uso terapêutico , Cimetidina/uso terapêutico , Protocolos Clínicos , Custos de Medicamentos , Quimioterapia Combinada , Herpes Zoster/epidemiologia , Humanos , Neuralgia/epidemiologiaRESUMO
Under normal conditions acute stimulation and sensitization of polymodal nociceptive C-fibres cause pain and, due to afferent axon reflex activation, a local skin vasodilatation, flare reaction and skin temperature increase. Two questions arise: (i) Do sensitized C-nociceptors signal allodynia in chronic postherpetic neuralgia? (ii) If not, does ongoing peripheral nociceptive C-fibre input maintain a central process that accounts for allodynia? Ten patients with postherpetic neuralgia and tactile allodynia and 10 control subjects were studied using a laser Doppler perfusion monitor. Peripheral nociceptive C-fibre function was assessed by quantitative measurement of the axon reflex vasodilatation and flare reaction induced by histamine iontophoresis and compared with non-neural vasodilatation induced by local skin heating. Resting skin temperature, skin resistance and resting skin blood flow were the same in the allodynic area and the contralateral homologous skin area. The histamine responses (vasodilatation and flare) were significantly reduced or nearly abolished in the allodynic area compared with the contralateral side, whereas the temperature-dependent vasodilatation in patients and the histamine responses in healthy controls showed no side differences. C-fibre mediated pain and itch sensations were also decreased in the allodynic area. These findings indicate a considerable impairment of cutaneous nociceptive C-fibre function in the allodynic area. Allodynic stimuli of 20 s did not cause any local blood flow change. Impairment of C-fibre function was positively correlated with intensity of neuropathic pain. We conclude that sensitized nociceptive C-fibres are not involved in signalling allodynia. Changes in CNS processing may occur after zoster infection that strengthen the synaptic ties between central pain signalling pathways and low-threshold mechanoreceptors with A beta-fibres. This altered central processing is not maintained by ongoing cutaneous nociceptive C-fibre input, at least in some patients with postherpetic neuralgia. On the contrary, an anatomical synaptic reorganization depending on afferent C-fibre degeneration seems to be more likely, particularly in advanced stages of postherpetic neuralgia.