Thermal sensitivity across ages and during chronic fentanyl administration in rats

Abstract

Rationale 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. Objectives Thus the present preclinical study assessed the effectiveness of chronic fentanyl administration to produce antinociception in aging rats (16, 20, 24 months). Methods 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. Results 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. Conclusions Overall, aging modifies the behavioral effects of opioids, a finding that may inform future studies for devising appropriate treatment strategies.

Divergent profiles of fentanyl withdrawal and associated pain in mice and rats

“…During spontaneous withdrawal, fentanyl exposed rats and mice both lost weight. This may be an effect of withdrawal, or of repeated drug exposure, since chronic fentanyl and morphine exposure (both intermittent and continuous) lead to weight loss 32,33,60,61 .…”

“…Morphine withdrawal hyperalgesia has been shown in male C57Bl6/J mice tested on a cold plate 77 . One group reported minimal effects of chronic fentanyl exposure and withdrawal on cold sensitivity in aged rats 60 . Here, we use the acetone test to measure cold sensitivity 78,79 .…”

The effects of aging on hydromorphone-induced thermal antinociception in healthy female cats

“…The effects of age on opioid-induced magnitude of antinociception have been previously evaluated in rats 6,8,9,22,31,32,39,40,48,50 and mice. 11,20 It is difficult to draw relevant conclusions based on previous studies mostly because of differences in study methodology.…”

“…However, there is currently a lack of studies on the subject. 17,31,32,39,40 For example, adult rats (18–24 months of age) have demonstrated increased antinociceptive effects of µ- and κ-opioid receptor agonists when compared with young rats (3–6 months of age). 22,40,48 Contrarily, reduced antinociceptive effects of opioids were observed in other studies as rats mature to adulthood.…”

“…22,40,48 Contrarily, reduced antinociceptive effects of opioids were observed in other studies as rats mature to adulthood. 8,9,24,25,31,32 Due to the inconsistencies reported, additional research is required to determine the antinociceptive effects of opioids in pediatric and adult subjects. Ideally, the same group of subjects should be used to allow better data comparisons.…”