Animal Studies on the Spinal Action of Opiates in Analgesia

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Animal studies demonstrated that the local action of opiates in the spinal cord would produce a highly significant elevation in the nociceptive threshold in a variety of species including the rat, cat and primate. Two important aspects of this observation were that first the effects were related to a change in the pain threshold, with little effects being observed on motor function, or autonomic activity. The second major observation, was that this effect of spinal opiates was mediated through its effects on a specific receptor system. Evidence for this derives from the fact that these effects of spinal opiates are 1.dose dependent, 2. stereospecific, 3. characterized by a precise structure activity relationship and 4. antagonized in a dose dependent fashion by opioid antagonists. The physiological correlate of this behaviorally defined analgesia appears to be reflected in the fact that systemic opiates will antagonize the discharge of nociceptive neurons in the spinal cord evoked by small, but not large fiber stimulation. The fact that opiates will antagonize the release of substance P, an 11 amino acid peptide thought to mediate small afferent synaptic transmission, may underlie some of the analgetic effects of spinal opiates. Future directions in analgetic therapy may derive from the fact that other intrinsic modulatory systems exist within the spinal gray.