Pain-depressing agents and the spinal nociceptive system.

The spinal nociceptive system is the target of various pain depressing agents. It is capable to function without control from the brain. It is activated by tissue damage which, by excitation of nociceptive afferents, evokes activity in axons ascending to the brain (sensory nociceptive response) and in spinal reflex pathways (motor and autonomic responses). The prototype of an analgesic agent, morphine, suppresses nociceptive responses by binding to opiate receptors; it imitates the effect of the transmitter(s) released from endorphinergic neurones. Pentobarbital and diazepam reduce nociceptive (and non-nociceptive) responses by acting on the GABA receptor complex; both drugs facilitate the effect of the transmitter GABA which mediates presynaptic inhibition in the spinal cord. Pentobarbital may produce its effects by an additional action on postsynaptic neurone membranes. Clonidine depresses nociceptive responses, probably by imitating the action of the inhibitory transmitter, noradrenaline. Substance P acts as a "synaptic modulator"; it may facilitate or inhibit nociceptive responses. Ceruletide and cholecystokinin octapeptide depress nociceptive motor responses but do not affect the nociceptive sensory response. This indicates that motor and sensory responses of the spinal nociceptive system are not rigidly linked together. With the help of appropriate drugs, it is possible to manipulate them separately.