Garner Jamani B, Marshall Laura S, Boyer Nathaniel M, Alapatt Vinaya, Miller Laurence L
Department of Psychological Sciences, Augusta University, Augusta, GA, United States.
Front Pain Res (Lausanne). 2021 Jun;2. doi: 10.3389/fpain.2021.673940. Epub 2021 Jun 8.
A primary goal in pain treatment is restoration of behaviors that are disrupted by pain. Measures of pain interference indicate the degree to which pain interferes with activities in pain patients, and these measures are used to evaluate the effects of analgesic drugs. As a result of the emphasis on the expression and treatment of functional impairment in clinical settings, preclinical pain researchers have attempted to develop procedures for evaluation of pain-related functional impairment in laboratory animals. The goal of the present study was to develop and validate a low cost procedure for the objective evaluation of pain-related depression of home cage behavior in mice. On test days, a 5 × 5 cm Nestlet was weighed prior to being suspended from the wire lid of the home cage of individually housed male and female ICR mice. Over the course of experimental sessions, mice removed pieces of the suspended Nestlet, and began to build a nest with the material they removed. Thus, the weight of the pieces of Nestlet that remained suspended at various time points in the session provided an indicator of the rate of this behavior. The results indicate that Nestlet shredding was stable with repeated testing, and shredding was depressed by intra-peritoneal injection of 0.32% lactic acid. The non-steroidal anti-inflammatory drug ketoprofen blocked 0.32% lactic acid-induced depression of shredding, but did not block depression of shredding by a pharmacological stimulus, the kappa opioid receptor agonist U69,593. The μ-opioid receptor agonist morphine did not block 0.32% lactic acid-induced depression of shredding when tested up to doses that depressed shredding in the absence of lactic acid. When noxious stimulus intensity was reduced by decreasing the lactic acid concentration to 0.18%, morphine was effective at blocking pain-related depression of behavior. In summary, the data from the present study support consideration of the Nestlet shredding procedure for use in studies examining mechanisms, expression, and treatment of pain-related functional impairment.
疼痛治疗的一个主要目标是恢复被疼痛扰乱的行为。疼痛干扰的测量指标表明疼痛对疼痛患者活动的干扰程度，这些指标用于评估镇痛药的效果。由于临床环境中强调功能障碍的表达和治疗，临床前疼痛研究人员试图开发评估实验动物疼痛相关功能障碍的程序。本研究的目的是开发并验证一种低成本程序，用于客观评估小鼠笼内行为中与疼痛相关的抑制情况。在测试日，将一个5×5厘米的巢材在悬挂于单独饲养的雄性和雌性ICR小鼠笼舍的金属丝笼盖上之前称重。在实验过程中，小鼠会撕下悬挂着的巢材碎片，并开始用撕下的材料筑巢。因此，在实验过程中不同时间点仍悬挂着的巢材碎片重量可作为这种行为速率的指标。结果表明，巢材撕碎行为在重复测试中是稳定的，腹腔注射0.32%乳酸会抑制撕碎行为。非甾体抗炎药酮洛芬可阻断0.32%乳酸诱导的撕碎行为抑制，但不能阻断药理学刺激物κ阿片受体激动剂U69,593诱导的撕碎行为抑制。μ阿片受体激动剂吗啡在测试至能在无乳酸情况下抑制撕碎行为的剂量时，不能阻断0.32%乳酸诱导的撕碎行为抑制。当通过将乳酸浓度降至0.18%来降低有害刺激强度时，吗啡可有效阻断与疼痛相关的行为抑制。总之，本研究的数据支持考虑将巢材撕碎程序用于研究疼痛相关功能障碍的机制、表达和治疗。
