Activation of micro, delta or kappa opioid receptors by DAMGO, DPDPE, U-50488 or U-69593 respectively causes antinociception in the formalin test in the naked mole-rat (Heterocephalus glaber).

Data available on the role of the opioid systems of the naked mole-rat in nociception is scanty and unique compared to that of other rodents. In the current study, the effect of DAMGO, DPDPE and U-50488 and U-69593 on formalin-induced (20 microl, 10%) nociception were investigated. Nociceptive-like behaviors were quantified by scoring in blocks of 5 min the total amount of time (s) the animal spent scratching/biting the injected paw in the early (0-5 min) and in the late (25-60 min) phase of the test. In both the early and late phases, administration of 1 or 5 mg/kg of DAMGO or DPDPE caused a naloxone-attenuated decrease in the mean scratching/biting time. U-50488 and U-69593 at all the doses tested did not significantly change the mean scratching/biting time in the early phase. However, in the late phase U-50488 or U-69593 at the highest doses tested (1 or 5 mg/kg or 0.025 or 0.05 mg/kg, respectively) caused a statistically significant and naloxone-attenuated decrease in the mean scratching/biting time. The data showed that mu, delta or kappa-selective opioids causes antinociception in the formalin test in this rodent, adding novel information on the role of opioid systems of the animal on pain regulation.

Stimulation of mu and delta opioid receptors induces hyperalgesia while stimulation of kappa receptors induces antinociception in the hot plate test in the naked mole-rat (Heterocephalus glaber).

The antinociceptive effects of highly selective mu (DAMGO), delta (DPDPE) and kappa (U-50488 and U-69593) opioid agonists were evaluated following intraperitoneal (i.p.) administration in the naked mole-rat. A hot plate test set at 60 degrees C was used as a nociceptive test and the latency to the stamping of the right hind paw (response latency) was used as the end-point. DAMGO (5-10 mg/kg) and DPDPE (2.5-5 mg/kg) caused a naloxone-reversible significant decrease in the mean response latency. Subcutaneous injection of naloxonazine (20 mg/kg) 24h prior to the administration of DAMGO (5 mg/kg) also blocked the reduction in the response latency observed when DAMGO was injected alone. On the contrary, U-50488 (2.5-5 mg/kg) or U-69593 (0.08 or 0.1 mg/kg) caused a naloxone-reversible significant increase in the mean response latency. These results showed that activation of mu or delta receptors caused hyperalgesia, whereas activation of kappa receptors caused antinociception in the hot plate test in naked mole-rat. This suggests that mu and delta receptors modulate thermal pain in a different way than kappa receptors in the naked mole-rat. It is not possible at the moment to point out how they modulate thermal pain as little is known about the neuropharmacology of the naked mole-rat.