Barattini Angela E, Gilpin Nicholas W, Pahng Amanda R
Southeast Louisiana Veterans Health Care System, New Orleans, LA, United States; Department of Physiology, LSU Health Sciences Center, New Orleans, LA, United States.
Southeast Louisiana Veterans Health Care System, New Orleans, LA, United States; Department of Physiology, LSU Health Sciences Center, New Orleans, LA, United States; Alcohol & Drug Abuse Center of Excellence, LSU Health Sciences Center, New Orleans, LA, United States; Neuroscience Center of Excellence, LSU Health Sciences Center, New Orleans, LA, United States.
Pharmacol Biochem Behav. 2024 Dec;245:173890. doi: 10.1016/j.pbb.2024.173890. Epub 2024 Oct 2.
The co-occurrence of chronic pain and opioid misuse has led to numerous preclinical investigations of pain-opioid interactions to examine how pain manipulations alter the reinforcing properties of opioids. However, preclinical investigations of chronic pain effects on opioid drug self-administration have produced inconsistent results. Our previous work demonstrated that established fentanyl self-administration is resistant to change by induction of chronic inflammatory pain (Complete Freund's Adjuvant; CFA) in male and female rats, while other laboratories have shown that CFA increased fentanyl self-administration in male but not female rats when pain induction precedes self-administration, which may be a critical factor in determining the effects of chronic pain on self-administration. The present study was designed similarly to Higginbotham et al. (2022) to test the effects of CFA on fentanyl self-administration in rats that underwent pain prior to acquisition of fentanyl self-administration. Male and female rats treated with hindpaw CFA or saline were trained to intravenously self-administer (IVSA) fentanyl for 3 weeks under limited access to fentanyl (2 h per day) conditions. After 3 weeks of fentanyl IVSA acquisition, we tested motivation to take fentanyl using progressive ratio testing and dose-response testing. CFA male and female rats self-administered less fentanyl than saline-treated controls during week 1 of acquisition, but not during weeks 2-3 of acquisition. Intra-session analysis of week 1 data demonstrated that chronic inflammatory pain suppressed fentanyl intake towards the end of week 1 and at the end of each operant session. We also report no effects of chronic inflammatory pain on motivation to take fentanyl. We discuss potential methodological explanations for differences between these results and prior reports. Our findings demonstrate that CFA temporarily suppresses fentanyl IVSA in animals without changing motivation to take fentanyl or promoting escalation of opioid use, suggesting that chronic inflammatory pain is unlikely to promote long-term risk of opioid misuse.
慢性疼痛与阿片类药物滥用的同时出现引发了众多关于疼痛 - 阿片类药物相互作用的临床前研究，以探究疼痛操纵如何改变阿片类药物的强化特性。然而，关于慢性疼痛对阿片类药物自我给药影响的临床前研究结果并不一致。我们之前的研究表明，在雄性和雌性大鼠中，已建立的芬太尼自我给药对慢性炎症性疼痛（完全弗氏佐剂；CFA）的诱导具有抗性，而其他实验室表明，当疼痛诱导先于自我给药时，CFA会增加雄性大鼠而非雌性大鼠的芬太尼自我给药，这可能是决定慢性疼痛对自我给药影响的关键因素。本研究的设计与希金博特姆等人（2022年）的研究相似，以测试CFA对在获得芬太尼自我给药之前经历疼痛的大鼠中芬太尼自我给药的影响。用后爪CFA或生理盐水处理的雄性和雌性大鼠在有限获取芬太尼（每天2小时）的条件下接受为期3周的静脉内自我给药（IVSA）芬太尼训练。在进行3周的芬太尼IVSA获取后，我们使用累进比率测试和剂量反应测试来测试获取芬太尼的动机。在获取的第1周，CFA处理的雄性和雌性大鼠自我给药的芬太尼比生理盐水处理的对照组少，但在获取的第2 - 3周则不然。对第1周数据的会话内分析表明，慢性炎症性疼痛在第1周结束时和每个操作会话结束时抑制了芬太尼的摄入量。我们还报告了慢性炎症性疼痛对获取芬太尼动机没有影响。我们讨论了这些结果与先前报告之间差异的潜在方法学解释。我们的研究结果表明，CFA会暂时抑制动物的芬太尼IVSA，而不会改变获取芬太尼的动机或促进阿片类药物使用的升级，这表明慢性炎症性疼痛不太可能促进阿片类药物滥用的长期风险。
