Effect of carbamazepine and gabapentin on excitability in the trigeminal subnucleus caudalis of neonatal rats using a voltage-sensitive dye imaging technique

BACKGROUND: The antiepileptic drugs carbamazepine and gabapentin are effective in treating neuropathic pain and trigeminal neuralgia. In the present study, to analyze the effects of carbamazepine and gabapentin on neuronal excitation in the spinal trigeminal subnucleus caudalis (Sp5c) in the medulla oblongata, we recorded temporal changes in nociceptive afferent activity in the Sp5c of trigeminal nerve-attached brainstem slices of neonatal rats using a voltage-sensitive dye imaging technique. RESULTS: Electrical stimulation of the trigeminal nerve rootlet evoked changes in the fluorescence intensity of dye in the Sp5c. The optical signals were composed of two phases, a fast component with a sharp peak followed by a long-lasting component with a period of more than 500 ms. This evoked excitation was not influenced by administration of carbamazepine (10, 100 and 1,000 µM) or gabapentin (1 and 10 µM), but was increased by administration of 100 µM gabapentin. This evoked excitation was increased further in low Mg²+ (0.8 mM) conditions, and this effect of low Mg²+ concentration was antagonized by 30 µM DL-2-amino-5-phosphonopentanoic acid (AP5), a N-methyl-D-as-partate (NMDA) receptor blocker. The increased excitation in low Mg²+ conditions was also antagonized by carbamazepine (1,000 µM) and gabapentin (100 µM). CONCLUSION: Carbamazepine and gabapentin did not decrease electrically evoked excitation in the Sp5c in control conditions. Further excitation in low Mg²+ conditions was antagonized by the NMDA receptor blocker AP5. Carbamazepine and gabapentin had similar effects to AP5 on evoked excitation in the Sp5c in low Mg²+ conditions. Thus, we concluded that carbamazepine and gabapentin may act by blocking NMDA receptors in the Sp5c, which contributes to its anti-hypersensitivity in neuropathic pain.

Phenylpyrazolone derivatives inhibit gastric emptying in rats by a capsaicin-sensitive afferent pathway

Dipyrone (Dp), 4-aminoantipyrine (AA) and antipyrine (At) administered iv and Dp administered icv delay gastric emptying (GE) in rats. The participation of capsaicin (Cps)-sensitive afferent fibers in this phenomenon was evaluated. Male Wistar rats were pretreated sc with Cps (50 mg/kg) or vehicle between the first and second day of life and both groups were submitted to the eye-wiping test. GE was determined in these animals at the age of 8/9 weeks (weight: 200-300 g). Ten minutes before the study, the animals of both groups were treated iv with Dp, AA or At (240 μmol/kg), or saline; or treated icv with Dp (4 μmol/animal) or saline. GE was determined 10 min after treatment by measuring percent gastric retention (GR) of saline labeled with phenol red 10 min after orogastric administration. Percent GR (mean ± SEM, N = 8) in animals pretreated with Cps and treated with Dp, AA or At (35.8 ± 3.2, 35.4 ± 2.2, and 35.6 ± 2 percent, respectively) did not differ from the GR of saline-treated animals pretreated with vehicle (36.8 ± 2.8 percent) and was significantly lower than in animals pretreated with vehicle and treated with the drugs (52.1 ± 2.8, 66.2 ± 4, and 55.8 ± 3 percent, respectively). The effect of icv administration of Dp (N = 6) was not modified by pretreatment with Cps (63.3 ± 5.7 percent) compared to Dp-treated animals pretreated with vehicle (62.3 ± 2.4 percent). The results suggest the participation of capsaicin-sensitive afferent fibers in the delayed GE induced by iv administration of Dp, AA and At, but not of icv Dp.

Mecanorreceptores cardíacos / Cardiac mechanoreceptors

Utilizou-se a noradrenalina na dose padräo de 2 ug/Kg, medindo-se o fluxo na artéria femoral antes e após o estímulo. A injeçäo foi feita em diversos níveis da aorta, intracardíaca e na veia axilar. Para estudar a dependência do fenômeno com as vias nervosas, estimularam-se cäes com os nervos femoral e ciático seccionados, com desnervaçäo dos seios carotídeos e aórtico e com os vagos seccionados bilateralmente. Foi possível observar que: 1 - O aumento da atividade cardíaca que se acompanha de aumento da contratilidade é estímulo eficaz para desencadear o aumento do fluxo na artéria femoral. O aumento da contratilidade cardíaca e a diminuiçäo da resistência periférica säo proporcionais à dose de noradrenalina injetada (dentro dos limites de 1 a 3 ug). 2- No cäo com uma pata posterior submetida à secçäo dos nervos femoral ciático, a injeçäo de noradrenalina causa diminuiçäo da resistência vascular na pata normal, simultaneamente com o aumento da resistência na pata desnervada. Essa observaçäo demonstra ser esse fenômeno um reflexo. 3- A secçäo dos seios carotídeos e aórticos quase näo influencia essa resposta reflexa. 4- A injeçäo de noradrenalina na artéria femoral e em diversas posiçöes da aorta näo causa diminuiçäo da resistência periférica. A injeçäo endovenosa no bulbo aórtico e intracardíaca (ventrículo esquerdo) sempre leva à vasodilataçäo na regiäo estudada. 5- A secçäo vagal deprime acentuadamente a resposta, demonstrando ser essa a principal via nervosa responsável pelo reflexo