Department of Health and Rehabilitation Sciences, University of Cape Town, Cape Town, Western Cape, South Africa.
Pain Unit, Department of Anaesthesia and Perioperative Medicine, Neuroscience Institute, University of Cape Town, Cape Town, Western Cape, South Africa.
PeerJ. 2022 Jun 20;10:e13512. doi: 10.7717/peerj.13512. eCollection 2022.
Pain is thought to be influenced by the threat value of the particular context in which it occurs. However, the mechanisms by which a threat achieves this influence on pain are unclear. Here, we explore how threat influences experimentally-induced secondary hyperalgesia, which is thought to be a manifestation of central sensitization. We developed an experimental study to investigate the effect of a manipulation of threat on experimentally-induced secondary hyperalgesia in 26 healthy human adults (16 identifying as female; 10 as male). We induced secondary hyperalgesia at both forearms using high-frequency electrical stimulation. Prior to the induction, we used a previously successful method to manipulate threat of tissue damage at one forearm (threat site). The effect of the threat manipulation was determined by comparing participant-rated anxiety, perceived threat, and pain during the experimental induction of secondary hyperalgesia, between the threat and control sites. We hypothesized that the threat site would show greater secondary hyperalgesia (primary outcome) and greater surface area (secondary outcome) of induced secondary hyperalgesia than the control site. Despite a thorough piloting procedure to test the threat manipulation, our data showed no main effect of site on pain, anxiety, or threat ratings during high-frequency electrical stimulation. In the light of no difference in threat between sites, the primary and secondary hypotheses cannot be tested. We discuss reasons why we were unable to replicate the efficacy of this established threat manipulation in our sample, including: (1) competition between threats, (2) generalization of learned threat value, (3) safety cues, (4) trust, and requirements for participant safety, (5) sampling bias, (6) sample-specific habituation to threat, and (7) implausibility of (sham) skin examination and report. Better strategies to manipulate threat are required for further research on the mechanisms by which threat influences pain.
疼痛被认为受到其发生的特定环境的威胁价值的影响。然而，威胁实现这种对疼痛的影响的机制尚不清楚。在这里，我们探讨了威胁如何影响实验性引起的继发性痛觉过敏，这被认为是中枢敏化的表现。我们开展了一项实验研究，以调查在 26 名健康成年人（16 名女性，10 名男性）中，对威胁的操纵对实验性引起的继发性痛觉过敏的影响。我们使用高频电刺激在两个前臂引起继发性痛觉过敏。在诱导之前，我们使用了一种以前成功的方法来操纵一个前臂（威胁部位）的组织损伤威胁。通过比较威胁部位和对照部位在实验性继发性痛觉过敏诱导期间参与者评定的焦虑、感知威胁和疼痛，来确定威胁操纵的效果。我们假设威胁部位的继发性痛觉过敏（主要结果）和诱导的继发性痛觉过敏的表面积（次要结果）会大于对照部位。尽管进行了彻底的试验程序来测试威胁操纵，但我们的数据显示，在高频电刺激期间，部位对疼痛、焦虑或威胁评定没有主要影响。鉴于部位之间没有威胁差异，主要和次要假设都不能进行检验。我们讨论了为什么我们无法在我们的样本中复制这种既定威胁操纵的有效性的原因，包括：（1）威胁之间的竞争，（2）学习威胁价值的泛化，（3）安全线索，（4）信任和参与者安全要求，（5）抽样偏差，（6）样本特定的威胁习惯化，以及（7）（假）皮肤检查和报告的不合理性。需要更好的威胁操纵策略来进一步研究威胁影响疼痛的机制。
