The Antinociceptive Role of ??- and ??-Opiate Receptors and Their Interactions in the Spinal Dorsal Horn of Cats

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Abstract
This study was undertaken to examine the antinociceptive roles of different subtypes of opiate receptors and their interactions at the level of the spinal cord. We recorded extracellularly the activity of the single wide dynamic range neurons evoked by noxious radiant heat (51.degree. C) in decerebrate, spinally transected cats. The separate intrathecal administration of DAGO (selective .mu.-agonist, n = 28), morphine (less selective .mu.-agonist, n = 22), DPDPE (selective .delta.-agonist, n = 25), and DADL (less selective .delta.-agonist, n = 17) produced statistically significant supression of noxiously evoked activity in a time- and dose-dependent manner. In addition, intravenously administratered naloxone (nonselective opiate antagonist) reversed the suppressive effects of all opiates studied. Intravenously administered ICI 174,864 (selective .delta.-anatagonist) reversed the effects of DPDPE. These results, based on relative selectivity for opiate receptors, indicate that both .mu.- and .delta.-opiate receptors can modulate the input of nociceptive information in the spinal dorsal horn. To study interactions between .mu.- and .delta.-receptors at the level of the spinal cord, a combination of the above agonists was injected intrathecally.sbd.namely, an ineffective or slightly effective dose of DAGO (1 or 1.5 .mu.g, respectively) that was combined with an ineffective dose of DPDPE (30 .mu.g). The intrathecal combination of DAGO and DPDPE produced significant synergistic suppressive effects of noxiously evoked activity. These findings, again based on relative selectivity, suggest that drug combinations that include both selective .mu.- and .delta.-agonists may be a useful method of lowering the total amount of any one drug, thus decreasing the likelihood of side effects, while at the same time producing significant analgesia. Clearly, combinations of other .mu.- and .delta.-agonists should be studied to confirm the utility of such combinations.