Spinal and supraspinal opioid analgesia in the mouse: the role of subpopulations of opioid binding sites

The selective in vivo blockade of high affinity (mu₁) opioid binding sites in mice by naloxazone reduced the analgesic potency of opiates and opioid peptides, evidenced by a shift of their analgesic ED₅₀ values. However, the extent of these shifts varied significantly between a series of opioid drugs, ranging from 12-fold for morphine to 4-fold for d-Ala²-d-Leu⁵-enkephalin. These findings suggested that analgesia in naloxazone-treated animals is mediated through a different subpopulation of receptors than in normal controls. Correlating these analgesic shifts for a series of opioids with their affinity for different [³H]opioid binding sites suggested an analgesic role for delta sites. Additional studies in mice with spinal transections suggested that mu₁ analgesia was primarily supraspinal.