Serrano Nidia Espinoza, Saputra Samuel G, Íbias Javier, Company Matthew, Nazarian Arbi
Department of Pharmaceutical Sciences, Western University of Health Sciences, 309 E. Second Street, Pomona, CA, 91766, USA.
Departamento de Metodologίa de Las Ciencias del Comportamiento, Facultad de Psicologίa, Universidad Nacional de Educacίon a Distancia (UNED), 28040, Madrid, Spain.
Psychopharmacology (Berl). 2021 Dec;238(12):3447-3462. doi: 10.1007/s00213-021-05963-z. Epub 2021 Aug 24.
Pain sensation can negatively impact cognitive function, including impulsivity. Pain-induced changes in impulsivity can contribute to development of psychiatric comorbidities found in those with chronic pain conditions. The goal of this study was to determine whether complete Freund's adjuvant (CFA)-induced pain manipulation enhances impulsivity in rats. Whether the pain-induced impulsivity is sexually dimorphic, and if mu-opioid receptors play a role in these processes.
Male and female rats were screened for trait impulsivity and designated as high or low impulsive using a delay discounting task. Rats then received a hind paw injection of CFA, and their impulsivity was assessed for 16 days. The effects of morphine on impulsivity were also examined. In a separate experiment, rats were pretreated with beta-funaltrexamine (β-FNA) to determine the role of mu-opioid receptors on impulsivity.
CFA treatment increased impulsivity in males and females. The onset of CFA-induced impulsivity was faster in high impulsive females than males. Morphine blocked CFA-induced impulsivity in both sexes in a dose- and time-dependent manner. β-FNA prevented the actions of morphine on CFA-induced impulsivity in high impulsive males, but not high impulsive females. Moreover, β-FNA increased CFA-induced impulsivity in morphine naïve males, but not females.
These findings demonstrate unique sex differences in CFA-induced impulsivity, response to morphine, and the impact of mu-opioid receptors. A better understanding of cognitive deficits and their mechanisms can provide insight into the development of substance abuse and psychiatric comorbidities that occur in people with chronic pain.
痛觉会对认知功能产生负面影响，包括冲动性。疼痛引起的冲动性变化可能导致慢性疼痛患者出现精神共病。本研究的目的是确定完全弗氏佐剂（CFA）诱导的疼痛处理是否会增强大鼠的冲动性。疼痛诱导的冲动性是否存在性别差异，以及μ-阿片受体在这些过程中是否起作用。
使用延迟折扣任务对雄性和雌性大鼠进行特质冲动性筛选，并将其指定为高冲动性或低冲动性。然后给大鼠后爪注射CFA，并在16天内评估其冲动性。还研究了吗啡对冲动性的影响。在另一个实验中，用β-氟纳曲酮（β-FNA）预处理大鼠，以确定μ-阿片受体对冲动性的作用。
CFA处理增加了雄性和雌性大鼠的冲动性。高冲动性雌性大鼠中CFA诱导的冲动性发作比雄性更快。吗啡以剂量和时间依赖性方式阻断了两性中CFA诱导的冲动性。β-FNA阻止了吗啡对高冲动性雄性大鼠中CFA诱导的冲动性的作用，但对高冲动性雌性大鼠无效。此外，β-FNA增加了未用过吗啡的雄性大鼠中CFA诱导的冲动性，但对雌性大鼠无效。
这些发现表明，在CFA诱导的冲动性、对吗啡的反应以及μ-阿片受体的影响方面存在独特的性别差异。更好地理解认知缺陷及其机制可以为慢性疼痛患者中物质滥用和精神共病的发展提供见解。
