Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich, Zurich, Switzerland.
Department of Neurology, University Hospital Bern, Inselspital, University of Bern, Bern, Switzerland.
J Neurophysiol. 2023 Aug 1;130(2):436-446. doi: 10.1152/jn.00064.2023. Epub 2023 Jul 5.
Modulated autonomic responses to noxious stimulation have been reported in experimental and clinical pain. These effects are likely mediated by nociceptive sensitization, but may also, more simply reflect increased stimulus-associated arousal. To disentangle between sensitization- and arousal-mediated effects on autonomic responses to noxious input, we recorded sympathetic skin responses (SSRs) in response to 10 pinprick and heat stimuli before (PRE) and after (POST) an experimental heat pain model to induce secondary hyperalgesia (EXP) and a control model (CTRL) in 20 healthy females. Pinprick and heat stimuli were individually adapted for pain perception (4/10) across all assessments. Heart rate, heart rate variability, and skin conductance level (SCL) were assessed before, during, and after the experimental heat pain model. Both pinprick- and heat-induced SSRs habituated from PRE to POST in CTRL, but not EXP ( = 0.033). Background SCL (during stimuli application) was heightened in EXP compared with CTRL condition during pinprick and heat stimuli ( = 0.009). Our findings indicate that enhanced SSRs after an experimental pain model are neither fully related to subjective pain, as SSRs dissociated from perceptual responses, nor to nociceptive sensitization, as SSRs were enhanced for both modalities. Our findings can, however, be explained by priming of the autonomic nervous system during the experimental pain model, which makes the autonomic nervous system more susceptible to noxious input. Taken together, autonomic readouts have the potential to objectively assess not only nociceptive sensitization but also priming of the autonomic nervous system, which may be involved in the generation of distinct clinical pain phenotypes. The facilitation of pain-induced sympathetic skin responses observed after experimentally induced central sensitization is unspecific to the stimulation modality and thereby unlikely solely driven by nociceptive sensitization. In addition, these enhanced pain-induced autonomic responses are also not related to higher stimulus-associated arousal, but rather a general priming of the autonomic nervous system. Hence, autonomic readouts may be able to detect generalized hyperexcitability in chronic pain, beyond the nociceptive system, which may contribute to clinical pain phenotypes.
已经有研究报道称，在实验和临床疼痛中存在对有害刺激的调制自主反应。这些效应可能是由伤害感受敏化介导的，但也可能更简单地反映出与刺激相关的唤醒增加。为了区分伤害感受敏化和唤醒对有害输入引起的自主反应的影响，我们在 20 名健康女性中记录了 10 个针刺痛和热刺激前后（PRE 和 POST）的交感皮肤反应（SSR），以在实验性热痛模型（EXP）和对照模型（CTRL）中诱导继发性痛觉过敏（EXP 和 CTRL）。在所有评估中，针刺痛和热刺激均单独适应于疼痛感知（4/10）。在实验性热痛模型之前、期间和之后评估心率、心率变异性和皮肤电导水平（SCL）。在 CTRL 中，针刺痛和热诱导的 SSR 从 PRE 到 POST 都有习惯化，但在 EXP 中没有（ = 0.033）。与 CTRL 条件相比，在 EXP 中，背景 SCL（在刺激应用期间）在针刺痛和热刺激期间升高（ = 0.009）。我们的研究结果表明，在实验性疼痛模型后增强的 SSR 既不完全与主观疼痛相关，因为 SSR 与感知反应分离，也与伤害感受敏化无关，因为两种模式的 SSR 都增强了。然而，我们的研究结果可以通过实验性疼痛模型期间自主神经系统的启动来解释，这使得自主神经系统更容易受到有害输入的影响。总之，自主反应有可能不仅客观评估伤害感受敏化，还评估自主神经系统的启动，这可能与不同的临床疼痛表型的产生有关。在实验性中枢敏化后观察到的疼痛诱导的交感皮肤反应的促进作用与刺激方式无关，因此不太可能仅由伤害感受敏化驱动。此外，这些增强的疼痛诱导的自主反应也与更高的与刺激相关的唤醒无关，而是自主神经系统的一般启动。因此，自主反应可能能够检测到慢性疼痛中超越伤害感受系统的普遍过度兴奋，这可能有助于临床疼痛表型。
