Thomaidou Mia Athina, Veldhuijzen Dieuwke Swaantje, Peerdeman Kaya Joanne, Wiebing Naomi Zoë Sifra, Blythe Joseph Sullivan, Evers Andrea Walbruga Maria
Health, Medical and Neuropsychology Unit, Leiden University, Leiden, the Netherlands.
Leiden Institute for Brain & Cognition, Leiden, the Netherlands.
Pain. 2020 Jul;161(7):1597-1608. doi: 10.1097/j.pain.0000000000001861.
Nocebo hyperalgesia is a clinically relevant phenomenon and may be formed as a result of associative learning, implemented by classical conditioning. This study explored for the first time distinct nocebo conditioning methods and their consequences for nocebo attenuation methods. Healthy participants (N = 140) were recruited and randomized to the following nocebo hyperalgesia induction groups: conditioning with continuous reinforcement (CRF), conditioning with partial reinforcement (PRF), and a sham-conditioning control group. In the attenuation phase, counterconditioning was compared with extinction. During induction, participants experienced increased thermal pain in 100% of nocebo trials in the CRF groups, while in only 70% of nocebo trials in the PRF groups. During evocation, pain stimulation was equivalent across all trials. During attenuation, pain stimulation was decreased on nocebo trials relative to control trials for the counterconditioning groups, while pain remained equivalent across all trials for the extinction groups. Results showed that both PRF and CRF significantly induced nocebo hyperalgesia, but CRF was a more potent nocebo induction method, as compared to PRF. Counterconditioning was more effective than extinction in attenuating nocebo hyperalgesia. Neither CRF nor PRF resulted in resistance to extinction. However, compared with CRF, conditioning with PRF resulted in more resistance to counterconditioning. These findings demonstrate that the more ambiguous learning method of PRF can induce nocebo hyperalgesia and may potentially explain the treatment resistance and chronification seen in clinical practice. Further research is required to establish whether attenuation with counterconditioning is generalizable to clinical settings.
安慰剂性痛觉过敏是一种具有临床相关性的现象，可能是由经典条件作用所实现的联想学习形成的。本研究首次探索了不同的安慰剂性条件作用方法及其对安慰剂性痛觉过敏缓解方法的影响。招募了健康参与者（N = 140）并将其随机分为以下安慰剂性痛觉过敏诱导组：连续强化条件作用（CRF）组、部分强化条件作用（PRF）组和假条件作用对照组。在缓解阶段，将对抗条件作用与消退进行比较。在诱导阶段，CRF组100%的安慰剂试验中参与者的热痛增加，而PRF组仅70%的安慰剂试验中出现这种情况。在激发阶段，所有试验中的疼痛刺激是等效的。在缓解阶段，对抗条件作用组的安慰剂试验中疼痛刺激相对于对照试验有所降低，而消退组所有试验中的疼痛保持等效。结果表明，PRF和CRF均显著诱导了安慰剂性痛觉过敏，但与PRF相比，CRF是一种更强效的安慰剂诱导方法。在减轻安慰剂性痛觉过敏方面，对抗条件作用比消退更有效。CRF和PRF均未导致对消退的抵抗。然而，与CRF相比，PRF条件作用导致对对抗条件作用的抵抗更强。这些发现表明，PRF这种更模糊的学习方法可诱导安慰剂性痛觉过敏，并可能潜在地解释临床实践中所见的治疗抵抗和慢性化现象。需要进一步研究以确定对抗条件作用的缓解方法是否可推广到临床环境。
