GDNF induces mechanical hyperalgesia in muscle by reducing IBK in isolectin B4-positive nociceptors

We have assessed the mechanism underlying glial cell-derived neurotrophic factor (GDNF)-induced mechanical hyperalgesia in the gastrocnemius muscle, using patch clamp electrophysiology, in vivo electrophysiology and behavioral studies. Cultured isolectin B4-positive (IB4+) dorsal root ganglion neurons that innervated this muscle were held under current clamp; the majority developed an increase in action potential duration (a factor of increase of 2.29±0.24, compared to 1.13±0.17 in control, P<0.01) in response to GDNF (200 ng/ml) by 15 min after application. They also demonstrated a depolarization of resting membrane potential, but without significant changes in rheobase, action potential peak, or after-hyperpolarization. Large-conductance voltage- and calcium-activated potassium (BK) channels, which have recently been shown to play a role in the repolarization of IB4+ nociceptors, were inhibited under voltage clamp, as indicated by a significant reduction in the iberiotoxin-sensitive current. In vivo single-fiber recording from muscle afferents revealed that injection of iberiotoxin into their peripheral nociceptive field caused an increase in nociceptor firing in response to a 60s suprathreshold stimulus (an increase from 392.2±119.8 spikes to 596.1±170.8 spikes, P<0.05). This was observed in the absence of changes in the mechanical threshold. Finally, injection of iberiotoxin into the gastrocnemius muscle produced dose-dependent mechanical hyperalgesia. These data support the suggestion that GDNF induces nociceptor sensitization and mechanical hyperalgesia, at least in part, by inhibiting BK current in IB4+ nociceptors

Detection of Cysticercus antigens and antibodies in cerbrospinal fluid of patients with chronic meningitis Detecção de antígenos e anticorpos de Cysticercus em fluido cerebrospinal de pacientes com meningite crônica

Chronic meningitism is a less frequent manifestation of neurocysticercosis caused by Taenia solium cysticerci. In the present study we used Co-agglutination (Co-A), a simple and rapid slide agglutination test to detect specific Cysticercus antigen in the 67 cerebrospinal fluid (CSF) samples from patients with chronic meningitis of unknown etiology. The results were compared with that of ELISA for detection of antibodies. Among these samples four (5.97%) were positive for Cysticercus antigen by Co-A test and six (8.95%) were positive for antibodies by ELISA. Two samples were positive by both Co-A and ELISA, two were positive only by Co-A and four were positive only by ELISA. In the present study, although Cysticercus antigen and antibodies were present in CSF samples from eight (11.94%) patients, we cannot affirm that all the cases of chronic meningitis are due to cysticercosis, but for any case of chronic meningitis of unknown origin, it would be useful to consider the possibility of cysticercal meningitis.<br>Meningite crônica é manifestação pouco freqüente de neurocisticercose causada por cisticerco de Taenia solium. No presente estudo utilizamos co-aglutinação (Co-A) um teste simples e rápido de aglutinação para detectar antígeno específico de Cysticercus nas 67 amostras de fluido cerebrospinal (CSF) de pacientes com meningite crônica de etiologia desconhecida. Os resultados foram comparados com os de ELISA para detecção de anticorpos. Dentre estas amostras quatro (5,97%) foram positivas para antígenos de Cysticercus pelo teste Co-A e seis (8,95%) foram positivas para anticorpos por ELISA. Duas amostras foram positivas por ambos Co-A e ELISA, duas foram positivas somente por Co-A e quatro foram positivas somente por ELISA. No presente estudo embora antígenos e anticorpos de Cysticercus estivessem presentes nas amostras de CSF de oito pacientes (11,94%), não podemos afirmar que todos os casos de meningite crônica sejam devidos à cisticercose, mas para qualquer caso de meningite crônica de origem desconhecida seria útil considerar a possibilidade de meningite por cisticerco