Brice-Tutt Ariana C, Montgomery Darrice S, Kramer Cassidy M, Novotny Peter M, Malphurs Wendi L, Sharma Abhisheak, Caudle Robert M, Bruijnzeel Adriaan W, Setlow Barry, Neubert John K, Murphy Niall P
Departments of Orthodontics, University of Florida, Gainesville, Florida, USA.
Department of Pharmaceutics, University of Florida, Gainesville, Florida, USA.
Res Sq. 2023 Mar 24:rs.3.rs-2679319. doi: 10.21203/rs.3.rs-2679319/v1.
Inter-relationships between pain sensitivity, drug reward, and drug misuse are of considerable interest given that many analgesics exhibit misuse potential. Here we studied rats as they underwent a series of pain- and reward-related tests: cutaneous thermal reflex pain, induction and extinction of conditioned place preference to oxycodone (0.56 mg/kg), and finally the impact of neuropathic pain on reflex pain and reinstatement of conditioned place preference. Oxycodone induced a significant conditioned place preference that was extinguished throughout repeated testing. Correlations identified of particular interest included an association between reflex pain and oxycodone-induced behavioral sensitization, and between rates of behavioral sensitization and extinction of conditioned place preference. Multidimensional scaling analysis followed by k-clustering identified three clusters: (1) reflex pain and the rate of change in reflex pain response throughout repeated testing, (2) basal locomotion, locomotor habituation, and acute oxycodone-stimulated locomotion, and (3) behavioral sensitization, strength of conditioned place preference, and rate of extinction. Nerve constriction injury markedly enhanced reflex pain but did not reinstate conditioned place preference. These results support the notion that behavioral sensitization relates to the acquisition and extinction of oxycodone seeking/reward, but suggest that generally cutaneous thermal reflex pain poorly predicts oxycodone reward-related behaviors except for behavioral sensitization.
鉴于许多镇痛药都有被滥用的可能性，疼痛敏感性、药物奖赏和药物滥用之间的相互关系备受关注。在此，我们对大鼠进行了一系列与疼痛和奖赏相关的测试：皮肤热反射痛、对羟考酮（0.56毫克/千克）条件性位置偏好的诱导和消退，以及最后神经病理性疼痛对反射痛和条件性位置偏好恢复的影响。羟考酮诱导出显著的条件性位置偏好，该偏好在反复测试中逐渐消退。特别值得关注的相关性包括反射痛与羟考酮诱导的行为敏化之间的关联，以及行为敏化率与条件性位置偏好消退之间的关联。多维标度分析随后进行k聚类，确定了三个集群：（1）反射痛以及在反复测试中反射痛反应的变化率，（2）基础运动、运动习惯化和急性羟考酮刺激的运动，以及（3）行为敏化、条件性位置偏好的强度和消退率。神经缩窄损伤显著增强了反射痛，但并未恢复条件性位置偏好。这些结果支持行为敏化与羟考酮寻求/奖赏的获得和消退相关的观点，但表明一般来说，除了行为敏化外，皮肤热反射痛很难预测与羟考酮奖赏相关的行为。
