| Research Abstract |
Experiment 1
Background : Intravenous administration of N-methyl-D-aspartate (NMDA) receptor antagonists reportedly reduces the MAC for inhalation anaesthetics. We study the effects on the minimum alveolar anaesthetic concentration (MAC) of isoflurane in rats of intrathecal administration of a non-NMDA receptor antagonist (CNQX), a metabotropic glutamate receptor antagonist (AP3), or the combination of NMDA receptor antagonist (APV) and a neurokinin-1(NK-1) receptor antagonist (CP96345, CP).
Methods : After Wistar rats (n=36) were fitted with indwelling intrathecal catheters, the MAC of isofluane was determined following intrathecal administration of CNQX at 10 ug, Ap3 at 10 ug, or a combination of APV at 0.01 ug to 1 ug with CP at 0.1 to 10ug. Subsequently a reversal dose of intrathecal NMDA with substance P (SP) was administered, MAC of isoflurane was redetermined.
Results : Neither CNQX nor AP3 reduced the MAC of isoflurane. APV at 0.01 ug plus CP at 1 ug, as well as AVP at 0.1 ug plus
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CP at 10 ug, reduced the MAC of isoflurane, respective reductions, 7.6 % and 14 % ; (p<0.05). Co-administration of NMDA plus SP reversed the decrease in the MAC of isoflurane.
Conclusions : The NMDA receptor and the NK-1 receptor are important determinants of the MAC of isoflurane, exerting this influence by inhibition of pain transmission in the spinal cord, while mGlu and AMPA receptors have no effect on the MAC of isoflurane.
Experiment 2
We examined somatosensory evoked potential (SEP), locomotion and vocalisation upon tail pinch in rats in order to determine whether intrathecal magnesium sulphate administration cause spinal anaesthesia. In Wistar rats fitted with indwelling intrathecal catheters, cortical SEP was recorded following stimulation via electrodes inserted into the right hind paw under chloral hydrate anaesthesia before and after intrathecal administration of 10 ul of either magnesium sulphate (12.3% or 24.6%) or lidocaine (4% or 8%).
We tested locomotion and vocalisation after tail pinch following intrathecal administration of the same two drugs in conscious rats. SEP amplitude was diminished after administration of lidocaine (p<0.05), but after magnesium sulphate, amplitude did not change. Latency of P1 was increased by lidocaine and by 12.3% magnesium sulphate (p<0.05). Although lower extremity paralysis was observed in both groups, its duration with magnesium sulphate was much longer than with lidocaine. Vocalisation was recognized after 12.3% magnesium, but was not observed after 8 % lidocaine during paralysis (p<0.05). We believe that magnesium sulphate induced motor paralysis, but not complete analgesia.
Experiment 3
We examined the antinociceptive effect of intrathecally administered MgSO4 in rats, using acute pain models including mechanical pressure, heats and subcutaneous formalin injection. According to locomotion test, 10 ul of 6.2% MgSO4 did not produce motor nerve paralysis. At the same dose, responses to pressure or heat were intact, as controls given saline. MgSO4 produced depression of responses to pain only after the first 10 min in the formalin test. Our studies indicated that MgSO4 did not show remarkable antinociceptive effects in acute pain models. Less
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