Assistance Publique - Hôpitaux de Paris, Groupe Hospitalier Pitié Salpêtrière Charles Foix, Service de Pneumologie et Réanimation Médicale, Paris, France;
J Appl Physiol (1985). 2013 Sep 1;115(5):697-703. doi: 10.1152/japplphysiol.00027.2013. Epub 2013 Jul 18.
Experimentally induced pain can be attenuated by concomitant heterotopic nociceptive stimuli (counterirritation). Animal data indicate that this stems from supraspinal "diffuse noxious inhibitory controls" (DNICs) triggered by C and Aδ fibers. In humans, only noxious stimuli induce counterirritation. This points at C fibers, but the effects of pharmacologically stimulating C fibers have not been studied. Intravenous adenosine activates pulmonary C fibers and induces dyspnea. This study tests the hypothesis that putative activation of pulmonary C fibers by adenosine would trigger DNICs in humans and induce counterirritation. Twelve healthy volunteers were included (with valid results available in 9) and studied according to a double-blind, randomized, cross-over design (intravenous adenosine, 140 μg·kg(-1)·min(-1), during 5 min vs. placebo). We measured ventilatory variables and end-tidal CO2 tension, dyspnea intensity by visual analog scale, and the intensity of putative chest pain. The primary outcome was the amplitude of the RIII component of the nociceptive flexor reflex recorded by biceps femoris electromyogram in response to painful electrical sural nerve stimulation (RIII), taken as a substitute for pain perception. Placebo did not induce any significant effect. Adenosine induced dyspnea, hyperpnea, tachycardia, and significant RIII inhibition (24 ± 8% at the 4th min, P < 0.0001). The temporal dynamics of adenosine-induced dyspnea and RIII inhibition differed (immediate onset followed by a slow decrease for dyspnea, slower onset for RIII inhibition). Intravenous adenosine in normal humans induces counterirritation, fueling the notion that C-fiber stimulation trigger DNICs in humans. The temporal dissociation between adenosine-induced dyspnea and RIII inhibition suggests that C fibers other than pulmonary ones might be involved.
实验性疼痛可以通过同时给予异源性伤害性刺激（反刺激）来减轻。动物数据表明，这源于脊髓上的“弥散性伤害性抑制控制”（DNICs），由 C 和 Aδ 纤维触发。在人类中，只有伤害性刺激才能引起反刺激。这表明与 C 纤维有关，但尚未研究用药理学刺激 C 纤维的效果。静脉内腺苷激活肺 C 纤维并引起呼吸困难。这项研究检验了假设，即腺苷对肺 C 纤维的假定激活会在人类中触发 DNICs 并引起反刺激。纳入了 12 名健康志愿者（9 名志愿者有有效结果），并根据双盲、随机、交叉设计进行研究（静脉内给予腺苷，140μg·kg(-1)·min(-1)，持续 5 分钟，与安慰剂比较）。我们测量了通气变量和呼气末二氧化碳张力、通过视觉模拟量表评估呼吸困难强度以及推测性胸痛强度。主要结果是肱二头肌肌电图记录的伤害性屈肌反射的 RIII 成分的幅度，作为疼痛感知的替代物。安慰剂没有引起任何显著影响。腺苷引起呼吸困难、通气过度、心动过速和显著的 RIII 抑制（第 4 分钟时抑制 24±8%，P<0.0001）。腺苷诱导的呼吸困难和 RIII 抑制的时间动态不同（呼吸困难立即出现，然后缓慢减少，而 RIII 抑制则较慢出现）。在正常人类中，静脉内给予腺苷可引起反刺激，这支持了 C 纤维刺激可在人类中触发 DNICs 的观点。腺苷诱导的呼吸困难和 RIII 抑制之间的时间分离表明，可能涉及除肺以外的 C 纤维。
