Morphine Antinociceptive Potency on Chemical, Mechanical, and Thermal Nociceptive Tests in the Rat

Many tests are used to assess nociception in laboratory animals. The objective of this study was to compare morphine potency across tests. Rats were injected with saline or morphine (1-20 mg/kg SC), and nociception was assessed 15-20 min later. A consistent definition of antinociception—a change in response greater than 4 times the standard deviation above the mean for the saline-treated controls—was used to compare morphine potency on different tests. These data revealed 4 things. 1) Morphine potency was greatest on the paw pressure, hot plate, and tail withdrawal tests and lowest on the formalin test. 2) Stimulus intensity had no effect on morphine potency on the hot plate (ED50 = 4.5, 2.8, and 2.6 mg/kg for 49°C, 52°C, and 55°C tests, respectively) or tail withdrawal tests (ED50 = 2.9 and 2.6 for 48°C and 52°C water, respectively). 3) Assessment of morphine potency using a within-subjects cumulative dosing procedure resulted in lower ED50 values compared to data collected using a between-subjects design (hot plate: 2.6 vs 4.9; tail withdrawal: 2.6-2.9 vs 5.7 mg/kg). 4) Adjusting the cutoff value from 4 to 5, 6, 7, and 8 standard deviations greater than the mean resulted in a progressive increase in ED50 values. These data demonstrate that morphine potency is dependent, in part, on the nociceptive test even when all other factors (eg, species, strain, age, gender, and cutoff value) are held constant.PerspectiveThe ability of morphine to block nociception is influenced by many factors. The present study shows that the test used to assess nociception, but not the stimulus intensity, can have a dramatic effect on morphine potency. This finding shows that morphine potency varies depending on how pain is assessed.