Thermal sensitivity across ages and during chronic fentanyl administration in rats

Chronic pain is becoming a more common medical diagnosis and is especially prevalent in older individuals. As such, prescribed use of opioids is on the rise, even though the efficacy for pain management in older individuals is unclear. Thus, the present preclinical study assessed the effectiveness of chronic fentanyl administration to produce antinociception in aging rats (16, 20, and 24 months). Animals were tested in a thermal sensitivity procedure known to involve neural circuits implicated in chronic pain in humans. Sensitivity to heat and cold thermal stimulation was assessed during 28 days of fentanyl administration (1.0 mg/kg/day), and 28 days of withdrawal. Fentanyl resulted in decreased thermal sensitivity to heat but not cold stimulation indicated by more time spent in the hot compartment relative to time spent in the cold or neutral compartments. Unlike previous findings using a hot-water tail withdrawal procedure, tolerance did not develop to the antinociceptive effects of fentanyl over a 28-day period of drug administration. The oldest animals were least sensitive, and the youngest animals most sensitive to the locomotor-stimulating effects of fentanyl. The effect on the antinociceptive response to fentanyl in the oldest group of rats was difficult to interpret due to profound changes in the behavior of saline-treated animals. Overall, aging modifies the behavioral effects of opioids, a finding that may inform future studies for devising appropriate treatment strategies.