Morphine Selectively Depresses the Slowest, NMDA-independent Component of C-fibre-evoked Synaptic Activity in the Rat Spinal Cord In Vitro

1460-9568

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

The effects of morphine on the depolarizing synaptic responses produced in motoneurons by electrical stimulation of primary sensory neurones have been recorded in hemisected spinal cord preparations (8- to 12-day-old rat pups). Morphine at concentrations of 0.1-20 μM reduced a slow, long-lasting (latency greater than 1 s, duration up to 10 s) component of the ventral root potential (VRP) evoked by C-fibre strength stimulation of the dorsal root. At 2μM the reduction in area of this slow synaptic potential was 71.7 ± 0.9% of control values (n= 15). The earliest components of the C-fibre strength VRP (the first 100 ms) and the responses to Aβ strength stimuli were unaffected by the opioid even at 10-20μM. The intermediate, NMDA receptor antagonist (D-AP5, 40μM)-sensitive component (which lasts 100-1000 ms) was reduced by 34 ± 2.2% of control (n= 15), which was significantly less than the reduction of the later NMDA-independent component (P 〈 0.001). Morphine (0.1-20 μM) also depressed the cumulative depolarization generated by the temporal summation of synaptic responses evoked by brief trains of C-fibre strength stimuli (1 or 10 Hz). A significantly greater reduction at the lower frequency of stimulation (56.3 ± 2.0%) than at the higher (20.3 ± 1.69%, n = 10, measured at 2 μM morphine) was found (P 〈 0.005). The effects of morphine were reversible upon wash-out or superfusion with the opioid receptor antagonist naloxone (2 μM). The depression in the C-fibre-evoked VRPs produced by the NMDA receptor antagonist D-AP5 (10-40 μM) was different from that produced by morphine, as D-AP5 only reduced a shorter latency component of the VRP (100 ms-1 s) and was equally effective in decreasing the cumulative depolarizations evoked by 1 and 10 Hz trains. The preferential effect of morphine on the longest latency and longest lasting components of the high-threshold VRP are discussed in relation to its possible site and mechanism of analgesic action.

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