Jergova Stanislava, Martinez Heidy, Hernandez Melissa, Schachner Benjamin, Gross Suzanne, Sagen Jacqueline
Miller School of Medicine, University of Miami, Miami, FL, United States.
Front Pain Res (Lausanne). 2021 Jun 21;2:675232. doi: 10.3389/fpain.2021.675232. eCollection 2021.
Therapeutic strategies targeting phantom limb pain (PLP) provide inadequate pain relief; therefore, a robust and clinically relevant animal model is necessary. Animal models of PLP are based on a deafferentation injury followed by autotomy behavior. Clinical studies have shown that the presence of pre-amputation pain increases the risk of developing PLP. In the current study, we used Sprague-Dawley male rats with formalin injections or constriction nerve injury at different sites or time points prior to axotomy to mimic clinical scenarios of pre-amputation inflammatory and neuropathic pain. Animals were scored daily for PLP autotomy behaviors, and several pain-related biomarkers were evaluated to discover possible underlying pathological changes. Majority displayed some degree of autotomy behavior following axotomy. Injury prior to axotomy led to more severe PLP behavior compared to animals without preceding injury. Autotomy behaviors were more directed toward the pretreatment insult origin, suggestive of pain memory. Increased levels of IL-1β in cerebrospinal fluid and enhanced microglial responses and the expression of NaV1.7 were observed in animals displaying more severe PLP outcomes. Decreased expression of GAD65/67 was consistent with greater PLP behavior. This study provides a preclinical basis for future understanding and treatment development in the management of PLP.
针对幻肢痛（PLP）的治疗策略所提供的疼痛缓解效果欠佳；因此，需要一个可靠且与临床相关的动物模型。PLP的动物模型基于去传入神经损伤并继发自切行为。临床研究表明，截肢前疼痛的存在会增加发生PLP的风险。在本研究中，我们使用了Sprague-Dawley雄性大鼠，在切断轴突之前，于不同部位或时间点注射福尔马林或进行神经缩窄损伤，以模拟截肢前炎症性和神经性疼痛的临床情况。每天对动物的PLP自切行为进行评分，并评估几种与疼痛相关的生物标志物，以发现可能潜在的病理变化。大多数动物在切断轴突后表现出一定程度的自切行为。与未经历先前损伤的动物相比，切断轴突前的损伤导致更严重的PLP行为。自切行为更倾向于预处理损伤的起源部位，提示存在疼痛记忆。在表现出更严重PLP结果的动物中，观察到脑脊液中IL-1β水平升高、小胶质细胞反应增强以及NaV1.7表达增加。GAD65/67表达降低与更严重的PLP行为一致。本研究为未来理解和治疗PLP提供了临床前基础。
