Alexander Khadijah S, Rodriguez Taylor R, Sarfo Amma N, Patton Tadd B, Miller Laurence L
Department of Psychological Sciences, Augusta University, Augusta, Georgia, USA.
Behav Pharmacol. 2019 Sep;30(6):463-470. doi: 10.1097/FBP.0000000000000469.
Pain is a significant public health problem, and assessment of pain-related impairment of behavior is a key clinical indicator and treatment target. Similar to opioids and NSAIDs, dopamine (DA) transporter inhibitors block pain-related depression of intracranial self-stimulation (ICSS) in rats. The primary goal of the present study was to determine if the effects of monoamine uptake inhibitors on pain-related depression of ICSS in rats extend to an assay of pain-related depression of nesting in mice. We hypothesized that the DA transporter-selective uptake inhibitor bupropion would block depression of nesting behavior produced by intraperitoneal injection of lactic acid, whereas selective serotonin transporter-selective citalopram, norepinephrine transporter-selective nisoxetine, and the mixed action selective serotonin transporter/norepinephrine transporter inhibitor milnacipran would be ineffective. Effects of the NSAID ketoprofen were also obtained to facilitate interpretation of the effects of the monoamine uptake inhibitors. Consistent with previous findings, ketoprofen blocked pain-related depression of nesting. In contrast, none of the monoamine uptake inhibitors blocked pain-related depression of nesting, although they all blocked pain-related stimulation of stretching. Unlike findings from studies of pain-related depression of ICSS, these results do not support consideration of DA uptake inhibitors for treatment of pain-related depression of behavior.
疼痛是一个重大的公共卫生问题，对疼痛相关行为损伤的评估是一项关键的临床指标和治疗目标。与阿片类药物和非甾体抗炎药类似，多巴胺（DA）转运体抑制剂可阻断大鼠颅内自我刺激（ICSS）中与疼痛相关的抑制作用。本研究的主要目的是确定单胺摄取抑制剂对大鼠ICSS中与疼痛相关的抑制作用是否也适用于小鼠筑巢行为中与疼痛相关的抑制作用检测。我们假设DA转运体选择性摄取抑制剂安非他酮可阻断腹腔注射乳酸所产生的筑巢行为抑制，而选择性5-羟色胺转运体选择性西酞普兰、去甲肾上腺素转运体选择性尼索西汀以及混合作用的选择性5-羟色胺转运体/去甲肾上腺素转运体抑制剂米氮平则无效。还获取了非甾体抗炎药酮洛芬的作用效果，以利于解释单胺摄取抑制剂的作用效果。与先前的研究结果一致，酮洛芬可阻断与疼痛相关的筑巢行为抑制。相比之下，尽管所有单胺摄取抑制剂均能阻断与疼痛相关的伸展刺激，但没有一种能阻断与疼痛相关的筑巢行为抑制。与ICSS中与疼痛相关抑制作用的研究结果不同，这些结果不支持将DA摄取抑制剂用于治疗与疼痛相关的行为抑制。
