Clinically employed opioid analgesics produce antinociception via μ-δ opioid receptor heteromers in Rhesus monkeys.

Morphine and related drugs are widely employed as analgesics despite the side effects associated with their use. Although morphine is thought to mediate analgesia through mu opioid receptors, delta opioid receptors have been implicated in mediating some side effects such as tolerance and dependence. Here we present evidence in rhesus monkeys that morphine, fentanyl, and possibly methadone selectively activate mu-delta heteromers to produce antinociception that is potently antagonized by the delta opioid receptor antagonist, naltrindole (NTI).

Effects of gonadal steroid hormone treatments on opioid antinociception in ovariectomized rhesus monkeys.

Rationale: Gonadal steroid hormones altered opioid antinociception under some conditions in rodents, and we reported previously that chronic estradiol enhanced kappa but not mu opioid antinociception in ovariectomized rhesus monkeys. Sex differences have also been observed in the antinociceptive effects of opioid agonists. These findings suggest that gonadal hormones may modulate opioid antinociception.

Genetic variance in nociception and its relationship to the potency of morphine-induced analgesia in thermal and chemical tests.

The perceived intensity of a painful stimulus is determined in part by the stimulus intensity and environmental conditions. The purpose of this study was to determine the influence of genetic factors in nociception and its contribution to the potency of morphine to produce antinociception. Eight inbred strains of mice were tested across a range of stimulus intensities in thermal (hot plate) and chemical irritant (acetic acid) nociceptive tests.