Harvie Daniel S, Meulders Ann, Madden Victoria J, Hillier Susan L, Peto Daniela K, Brinkworth Russell, Moseley G Lorimer
The Sansom Institute for Health Research, University of South Australia, Australia; CONROD, Menzies Health Institute QLD, Griffith University, Australia.
The Research Group on Health Psychology, Department of Psychology, University of Leuven, Belgium; Center for Excellence on Generalization Research in Health and Psychopathology, University of Leuven, Belgium.
Scand J Pain. 2016 Apr;11:11-18. doi: 10.1016/j.sjpain.2015.09.007. Epub 2015 Dec 1.
Non-nociceptive somatosensory input, such as tactile or proprioceptive information, always precedes nociceptive input during a painful event. This relationship provides clear opportunities for predictive associative learning, which may shape future painful experiences. In this differential classical conditioning study we tested whether pain-associated tactile cues (conditioned stimuli; CS) could alter the perceived intensity of painful stimulation, and whether this depends on duration of the CS-seeing that CS duration might allow or prevent conscious expectation.
Subjects underwent a classical differential conditioning task in which a tactile cue at location A (CS+) preceded painful electrical stimulation at location B (UShigh), whereas a tactile cue at location C (CS-) preceded non-painful electrical stimulation at location B (USlow). At test, we compared the pain evoked by a moderately painful stimulus (USmed) when preceded by either the CS+ or CS-. CS duration was manipulated between subjects. Participants were assigned to one of three groups: Long CS (4s, allowing conscious expectation), Short CS (110ms) and CS-US indistinguishable (20ms), preventing conscious expectation). We hypothesised that more pain would be evoked by the US when preceded by the CS+ relative to the CS-, and that the effect would be independent of CS duration.
Fifty-four healthy participants (31 females, age=26, SD=9) were included in the analysis. The hypotheses were supported in that more intense pain was evoked by the USmed when paired with the tactile CS+, than when paired with the tactile CS-; mean difference 3mm on a 150mm VAS (CI 0.4-4.8mm). CS duration did not moderate the effect. The effect was greater in those participants where calibration was optimal, as indicated by a relatively more painful UShigh.
We conclude that pain-associated tactile cues can influence pain, and that this effect is not dependent on stimulus duration. This suggests that explicit expectation is not a requirement for predictive cues to modulate pain. That the presence of the CS+ resulted in only a 5.3% higher intensity rating compared with the CS- may reflect a limitation of laboratory studies, where a limited number of trials, an artificial context and the use of experimental pain are likely to reveal only glimpses of what is clinically possible.
Pain-associated visual and auditory cues have been shown to enhance pain in laboratory and clinical scenarios, supposedly by influencing expectation of impending harm. We show that pain-associated somatosensory cues can also modulate pain and that this can occur independently of expectation. This points to a larger potential role for associative learning in the development and treatment of pain than has previously been considered. We suggest that research into associative mechanisms underpinning pain, as distinct from those that link pain to pain-related fear and avoidance, is worthwhile.
在疼痛事件中，非伤害性躯体感觉输入，如触觉或本体感觉信息，总是先于伤害性输入出现。这种关系为预测性联想学习提供了明确的机会，而预测性联想学习可能会塑造未来的疼痛体验。在这项差异经典条件反射研究中，我们测试了与疼痛相关的触觉线索（条件刺激；CS）是否会改变疼痛刺激的感知强度，以及这是否取决于CS的持续时间——鉴于CS持续时间可能会允许或阻止有意识的预期。
受试者接受了一项经典的差异条件反射任务，其中A位置的触觉线索（CS+）先于B位置的疼痛电刺激（高强度非条件刺激），而C位置的触觉线索（CS-）先于B位置的非疼痛电刺激（低强度非条件刺激）。在测试中，我们比较了在CS+或CS-之前出现的中等疼痛刺激（中等强度非条件刺激）所诱发的疼痛。CS持续时间在受试者之间进行了操纵。参与者被分配到三组中的一组：长CS组（4秒，允许有意识的预期）、短CS组（110毫秒）和CS-US难以区分组（20毫秒，阻止有意识的预期）。我们假设，与CS-相比，CS+之前出现时，非条件刺激会诱发更多的疼痛，并且这种效应将与CS持续时间无关。
54名健康参与者（31名女性，年龄=26岁，标准差=9）纳入分析。假设得到支持，即与触觉CS-配对时相比，与触觉CS+配对时，中等强度非条件刺激诱发的疼痛更强烈；在150毫米视觉模拟量表上平均差异为3毫米（可信区间0.4 - 4.8毫米）。CS持续时间并未调节该效应。在校准最佳的参与者中，该效应更大，这表现为相对更痛的高强度非条件刺激。
我们得出结论，与疼痛相关的触觉线索可以影响疼痛，并且这种效应不依赖于刺激持续时间。这表明明确的预期不是预测性线索调节疼痛的必要条件。与CS-相比，CS+的存在仅导致强度评分高5.3%，这可能反映了实验室研究的局限性，在实验室研究中，有限的试验次数、人为的环境以及使用实验性疼痛可能只会揭示临床上可能情况的一些端倪。
在实验室和临床场景中，与疼痛相关的视觉和听觉线索已被证明会增强疼痛，据推测这是通过影响对即将到来的伤害的预期来实现的。我们表明，与疼痛相关的躯体感觉线索也可以调节疼痛，并且这可以独立于预期而发生。这表明联想学习在疼痛的发生和治疗中所起的潜在作用比之前认为的更大。我们建议，对支撑疼痛的联想机制进行研究是有价值的，这与将疼痛与疼痛相关的恐惧和回避联系起来的机制不同。
