D-limonene exhibits superior antihyperalgesic effects in a ß-cyclodextrin-complexed form in chronic musculoskeletal pain reducing Fos protein expression on spinal cord in mice.

Chronic musculoskeletal pain is one of the main symptoms found in Fibromyalgia with unclear etiology and limited pharmacological treatment. The aim of this study was to complex LIM in ß-cyclodextrin (LIM-ßCD) and then evaluate its antihyperalgesic effect in an animal model of chronic musculoskeletal pain. Differential scanning calorimetry and scanning electron microscopy was used for the characterization of the inclusion complex. Male Swiss mice were used for experimental procedures where mechanical hyperalgesia, thermal hyperalgesia, muscular strength, Fos immunofluorescence was studied after induction of hyperalgesia. Mechanism of action was also investigated through tail flick test and capsaicin-induced nociception. Endothermic events and morphological changes showed that the slurry complex method was the best method for the complexation. After induction of hyperalgesia, the oral administration of LIM-ßCD (50mg/kg) significantly increased the paw withdrawal threshold compared to uncomplexed limonene. Fos immunofluorescence showed that both compounds significantly decreased the number of Fos-positive cells in the dorsal horn. In nociceptive tests, FLU was able to reverse the antinociceptive effect of LIM-ßCD. After intraplantar administration of capsaicin, LIM was able to significantly decrease time to lick. LIM-ßCD has antihyperalgesic action superior to its uncomplexed form, with possible action in the dorsal horn of the spinal cord. These results suggest the possible applicability of LIM, uncomplexed or complexed with ßCD, in conditions such as FM and neuropathic pain, for which there are currently only limited pharmacological options.

Efficacy of gabapentin in the improvement of pruritus and quality of life of patients with notalgia paresthetica.

BACKGROUND: notalgia paresthetica is a subdiagnosed sensory neuropathy presenting as a condition of intense itching and hyperchromic macule on the back that interferes with daily habits. OBJECTIVES: To determine the efficacy of treatment of notalgia paresthetica using oral gabapentin, assessing the degree of improvement in itching and influence on quality of life. Moreover, to evaluate the signs and symptoms associated with notalgia paresthetica. METHODS: We conducted an experimental, non-randomized, parallel, non-blinded study including 20 patients with clinical and histopathological diagnosis of notalgia paresthetica. After application of the visual analogue scale of pain adapted for pruritus and of the questionnaire of dermatology life quality index (DLQI), ten patients with visual analogue scale > 5 were given treatment with gabapentin at the dose of 300 mg/day for four weeks. The other ten were treated with topical capsaicin 0.025% daily for four weeks. After the treatment period, patients answered again the scale of itching. RESULTS: The use of gabapentin was responsible for a significant improvement in pruritus (p=0.0020). Besides itching and hyperchromic stain on the back, patients reported paresthesia and back pain. It was observed that the main factor in the worsening of the rash is heat. CONCLUSION: Gabapentin is a good option for the treatment of severe itching caused by nostalgia paresthetica.

Efficacy of gabapentin in the improvement of pruritus and quality of life of patients with notalgia paresthetica

BACKGROUND: notalgia paresthetica is a subdiagnosed sensory neuropathy presenting as a condition of intense itching and hyperchromic macule on the back that interferes with daily habits. OBJECTIVES: To determine the efficacy of treatment of notalgia paresthetica using oral gabapentin, assessing the degree of improvement in itching and influence on quality of life. Moreover, to evaluate the signs and symptoms associated with notalgia paresthetica. METHODS: We conducted an experimental, non-randomized, parallel, non-blinded study including 20 patients with clinical and histopathological diagnosis of notalgia paresthetica. After application of the visual analogue scale of pain adapted for pruritus and of the questionnaire of dermatology life quality index (DLQI), ten patients with visual analogue scale > 5 were given treatment with gabapentin at the dose of 300 mg/day for four weeks. The other ten were treated with topical capsaicin 0.025% daily for four weeks. After the treatment period, patients answered again the scale of itching. RESULTS: The use of gabapentin was responsible for a significant improvement in pruritus (p=0.0020). Besides itching and hyperchromic stain on the back, patients reported paresthesia and back pain. It was observed that the main factor in the worsening of the rash is heat. CONCLUSION: Gabapentin is a good option for the treatment of severe itching caused by nostalgia paresthetica. .

Unilateral eyelid angiofibroma with complete blepharoptosis as the presenting sign of tuberous sclerosis.

Tuberous sclerosis is a multisystem autosomal-dominant disease characterized by hamartomatous growths in the brain, skin, kidneys, eyes, and heart, but it may affect almost any organ. Retinal hamartomas are 1 of the major diagnostic criteria for tuberous sclerosis and occur in approximately 50% of patients. Nonretinal findings include angiofibromas of the eyelid, strabismus, and pseudo-colobomas of the lens and iris. We report a case of a newborn with congenital eyelid angiofibroma mimicking complete congenital blepharoptosis that was revealed by central nervous system imaging to be part of the tuberous sclerosis complex.

Treatment of tinnitus with acamprosate.

Acamprosate, a drug used to treat alcohol dependence, was first reported as a potential treatment for tinnitus in 2005. The drug may improve tinnitus by a dual mechanism of action, acting both as a glutamate antagonist and as a GABA agonist. It is suggested that its action may be both on the ear and the nervous system.

Benzodiazepines and GABAergics in treating severe disabling tinnitus of predominantly cochlear origin.

Severe disabling tinnitus (SDT) refers to a symptom severe enough to disrupt affected patients' routine and keep them from performing their daily activities. SDT of a predominantly central origin has been treated successfully with benzodiazepines and GABAergic drugs. Our aim was to test the control of SDT of predominantly cochlear origin by benzodiazepines and GABAergic drugs. We followed the format of a prospective, randomized, single-blind clinical trial at an academic tertiary-care hospital. We studied 30 patients, all with SDT of clear cochlear origin. We treated 10 patients with placebo (group 1), 10 with benzodiazepine drugs (group 2), and 10 with benzodiazepine and GABAergic drugs (group 3). We recorded a decrease in the annoyance and intensity of SDT as measured by a visual analog scale ranging from 1 (negligible) to 10 (unbearable). We found statistically significant improvement in comparing groups 2 and 3 with group 1 but found no significant difference when groups 2 and 3 were compared. Addition of GABAergic to benzodiazepine drugs does not modify the treatment results in SDT of a predominantly cochlear origin.

[Efficacy and tolerability of vigabatrin in West syndrome]. / Avaliação da eficácia e tolerabilidade da vigabatrina na síndrome de West.

UNLABELLED: West syndrome (WS) is a severe epileptic encephalopathy of childhood, characterized by spasms, developmental deterioration and hipsarhythymia. OBJECTIVE: To evaluate the safety and efficacy of vigabatrin (VGB) in the treatment of WS. METHOD: We evaluated every patient diagnosed with WS seen at the pediatric epilepsy clinic and exposed to VGB. Patients were interviewed according to a semistructured questionnaire and we analyzed gender, age, etiology (cryptogenic or symptomatic), associated diseases, age of seizure onset, neuroimaging findings, EEG prior and after VGB, use of other antiepileptic drugs, time for seizure control, electroretinogram, visual complaints, adverse events and family history of epilepsy. RESULTS: Twenty-three patients were evaluated, 16 boys, ages ranging from 1.25 years to 11.5 years (mean=5y3m). Sixteen (69.5%) patients were seizure free, five (22%) had partial seizure control and in two (8.5%) there was no improvement. Only one patient presented gabaergic retinopathy. Six (26%) patients presented adverse events: somnolence, aggressivity or retinopathy. Patients with seizure onset after 6 months of age presented better results after VGB introduction (p<0.05). There was no difference in seizure control according to duration of epilepsy before VGB treatment or etiology of the seizures (p>0.05). After VGB, no patient presented hipsarrhythymia and 50% had a normal EEG. CONCLUSION: Although VGB may be associated with serious adverse events such as gabaergic retinopathy, our results show that it should be considered in the treatment of WS.

Transtorno bipolar: tratando o episódio agudo e planejando a manutenção / Bipolar disorder: treating the acute episode and planning the maintenance

O transtorno bipolar do humor é considerado uma condição psiquiátrica grave e recorrente, tendo várias vezes um curso crônico e incapacitante. Levando-se em consideração sua natureza episódica, ao tratar o episódio agudo devemos sempre planejar a terapêutica de manutenção. Este artigo apresenta o caso de uma paciente com uma forma grave de transtorno bipolar, com uma longa história de doença, no momento hospitalizada por um episódio maníaco com sintomas disfóricos. A discussão que se segue é realizada no modelo de uma conferência clínica, com o comentário de dois experts na área, abordando vários aspectos relacionados a diagnóstico, evolução e tratamento do caso.

Avaliação da eficácia e tolerabilidade da vigabatrina na síndrome de West / Efficacy and tolerability of vigabatrin in West syndrome

A síndrome de West (SW) é uma epilepsia grave específica da infância, que se caracteriza pela tríade: espasmos em salvas, deterioração ou atraso neuropsicomotor e hipsarritmia ao eletrencefalograma. OBJETIVO: Avaliar a eficácia e segurança da vigabatrina (VGB) no tratamento da SW. MÉTODO: Foram sujeitos do estudo todos os pacientes com diagnóstico estabelecido de SW, que freqüentam ou freqüentaram o Ambulatório de Epilepsia Infantil do Hospital das Clínicas da UNICAMP, usam ou usaram VGB na tentativa de controlar as crises. Avaliamos sexo, idade, etiologia (sintomática ou criptogênica), doença(s) associada(s), idade do início dos espasmos, freqüência das crises antes e após o uso de VGB, achados de neuroimagem, EEG antes e depois do uso de VGB, medicações associadas, tempo para controle das crises, eletroretinograma, queixa visual após uso de VGB, efeitos adversos e história familial de epilepsia. RESULTADOS: Foram avaliados 23 pacientes, sendo 16 do sexo masculino. A idade variou entre 1ano e 3 meses a 11 anos e 5meses (média = 5anos e 3meses). Dezesseis (69,5 por cento) pacientes apresentaram controle completo das crises, 5 (22 por cento) tiveram controle parcial e em 2 (8,5 por cento) pacientes os espasmos não foram controlados. Apenas uma paciente teve retinopatia gabaérgica. Seis pacientes (26 por cento) apresentaram eventos adversos - sonolência, agressividade ou retinopatia. Os pacientes com o início da SW após 6 meses de idade apresentaram melhor resposta à VGB (p<0,05). Não houve diferença na resposta ao tratamento quanto ao tempo de introdução da VGB ou à etiologia (p>0,05). Após o tratamento com VGB, nenhum EEG apresentou hipsarritmia e 50 por cento normalizaram. CONCLUSÃO: Apesar do risco de retinopatia gabaérgica, os resultados acima mostram que o uso da VGB no controle dos espasmos infantis se justifica em pacientes com SW.

Effects of gabaergic drugs on reserpine-induced oral dyskinesia.

Recently we have described the antidyskinetic property of the GABA mimetic drugs valproic acid and topiramate on reserpine-induced oral dyskinesia. In this respect, oral dyskinesia has been associated with important neuropathologies. The present study investigates the effects of different doses of the GABA(A) agonist tetrahydroisoxazolopyridine (THIP), of the GABA(B) agonist baclofen as well as of the GABA(A) modulator diazepam on the manifestation of reserpine-induced orofacial dyskinesia. Male Wistar rats received two injections of vehicle or of 1mg/kg reserpine separated by 48 h. Twenty-four hours later, animals were acutely treated with vehicle or THIP (2, 4 or 8 mg/kg), baclofen (1, 2 or 4 mg/kg) or diazepam (1, 2 or 4 mg/kg) and were observed for quantification of oral dyskinesia and open-field general activity. In order to verify the effects of these drugs per se on spontaneous oral movements, male Wistar rats were acutely treated with vehicle, 8 mg/kg THIP, 4 mg/kg baclofen or 4 mg/kg diazepam and observed for quantification of oral dyskinesia. The two highest doses of THIP or of baclofen abolished the manifestation of reserpine-induced oral dyskinesia while the lowest dose of baclofen attenuated it. Diazepam did not modify reserpine-induced oral dyskinesia at any dose tested. The highest doses of these drugs did not modify spontaneous oral movements. Reserpine-induced decrease in open-field general activity was not modified by any of the doses of THIP and diazepam or by the two lowest doses of baclofen. The highest dose of baclofen potentiated the increase in the duration of immobility induced by reserpine. These results reinforce the involvement of GABAergic hypofunction in the expression of oral dyskinesias, and support the potential therapeutic use of THIP and baclofen in the treatment of oral dyskinesias.

Seizures induced by intracerebral administration of pyridoxal-5'-phosphate: effect of GABAergic drugs and glutamate receptor antagonists.

Pyridoxal-5'-phosphate (PLP), the cofactor of glutamate decarboxylase, paradoxically induces convulsions when injected intracranially in adult mammals. We have tested the effect of some GABAergic and antiglutamatergic drugs on the behavioral and electroencephalographic (EEG) seizures produced by intracerebroventricular (i.c.v.) microinjection of 1 micromol PLP in the rat. PLP induced barrel turning, running fits and tonic-clonic convulsions, which started 5-10 min after recovery from the anesthesia (halothane), peaked at 20 min and disappeared at about 50 min. These symptoms were accompanied by frequent high amplitude EEG spike burst discharges. Pyridoxal, pyridoxamine-5'-phosphate or deoxypyridoxine were ineffective. The i.c.v. microinjection of the GABAergic compounds muscimol, isoguvacine, aminooxyacetic acid or GABA itself, significantly protected against PLP effects. In contrast, the NMDA receptor antagonists MK-801 and the non-NMDA receptor antagonist NBQX, failed to protect and induced motor alterations and mortality. We conclude that a temporary decrease of the GABA(A) receptor function is involved in the convulsant effect of PLP. This decrease might be due to the formation of a Schiff base between the carbonyl group of PLP and the epsilon-amino group of a functionally crucial lysine residue located in one extracellular loop of the GABA(A) receptor.