Department of Psychiatry, University of Florida College of Medicine, Gainesville, FL, 32610, USA.
Psychopharmacology (Berl). 2014 Jan;231(1):75-84. doi: 10.1007/s00213-013-3208-4. Epub 2013 Jul 31.
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.
慢性疼痛正成为一种更为常见的医学诊断,尤其在老年人中更为普遍。因此,尽管老年人的疼痛管理效果尚不清楚,但阿片类药物的处方使用仍在增加。
本临床前研究评估了慢性芬太尼给药在衰老大鼠(16、20 和 24 个月)中产生镇痛作用的效果。
动物在热敏感性程序中进行测试,该程序涉及到与人类慢性疼痛相关的神经回路。在芬太尼给药(1.0mg/kg/天)的 28 天期间和停药的 28 天期间,评估对热和冷刺激的敏感性。
芬太尼导致对热刺激的敏感性降低,但对冷刺激的敏感性没有降低,这表现为相对于冷或中性隔间的时间,动物在热隔间中花费的时间更多。与以前使用热水尾巴撤退程序的发现不同,在 28 天的药物给药期间,对芬太尼的镇痛作用没有产生耐受性。最老的动物对芬太尼的运动刺激作用最不敏感,而最年轻的动物最敏感。由于盐水处理动物的行为发生了深刻变化,因此难以解释芬太尼对最老组大鼠的镇痛反应的影响。
总之,衰老改变了阿片类药物的行为效应,这一发现可能为设计适当的治疗策略提供信息。