Dessirier J M, Simons C T, Sudo M, Sudo S, Carstens E
Section of Neurobiology, Physiology and Behavior, University of California, Davis, California 95616, USA.
J Neurophysiol. 2000 Oct;84(4):1851-62. doi: 10.1152/jn.2000.84.4.1851.
Repeated application of capsaicin at a 1-min interstimulus interval (ISI) to the tongue induces a progressively increasing irritant sensation (sensitization), followed after a rest period by reduced sensitivity to further capsaicin (desensitization). Sequential reapplication of capsaicin induces irritation that eventually increases to initial levels: stimulus-induced recovery (SIR). In contrast, repeated application of nicotine elicits a declining irritant sensation across trials. To investigate possible neural correlates of these phenomena, we recorded from single units in superficial laminae of the dorsomedial trigeminal subnucleus caudalis (Vc) that responded to noxious thermal (54 degrees C) and chemical (1 M pentanoic acid) stimulation of the tongue of anesthetized rats. We then recorded responses to either capsaicin (330 microM) or nicotine (0.6 M), delivered either once, repeatedly at 1-min ISI, or continually by constant flow. After the initial capsaicin application and a rest period, the capsaicin was reapplied in the identical manner to test for SIR. The mean response of 14 Vc units to sequential application of pentanoic acid did not vary significantly across trials, indicating lack of tachyphylaxis or sensitization. The averaged response of 11 Vc units to repeated capsaicin increased significantly across the first eight trials and then plateaued. Following the rest period, spontaneous firing had returned to the precapsaicin level. With capsaicin reapplication, the averaged response increased again after a significant delay (due to desensitization), but did not reattain the peak firing rate achieved in the initial series (partial SIR). Constant-flow application of capsaicin induced an identical sensitization followed by nearly complete SIR. A single application of capsaicin induced a significant rise in firing in eight other units, but the rate of rise and maximal firing rate were both much lower compared with repetitive or constant-flow capsaicin. When capsaicin was reapplied once after the rest period, there was no change in firing rate indicating absence of SIR. These results indicate that maintenance of the capsaicin concentration induces a progressive increase in neuronal response that parallels sensitization. With recurrent capsaicin application, desensitization can be overcome to result in a delayed recovery of Vc responses similar to SIR. In contrast, the averaged response of 17 Vc units to repeated or constant-flow application of nicotine increased only over the first 3 min, and then decreased to spontaneous levels even as nicotine was still being applied. These results are consistent with the decrease in the perceived irritation elicited by sequential application of nicotine in humans.
以1分钟的刺激间隔（ISI）对舌头反复施加辣椒素会诱发逐渐增强的刺激感（致敏），在一段休息期后对进一步的辣椒素敏感性降低（脱敏）。依次重新施加辣椒素会诱发刺激，最终刺激增强至初始水平：刺激诱导恢复（SIR）。相比之下，反复施加尼古丁会使各试验中的刺激感逐渐下降。为了研究这些现象可能的神经关联，我们记录了麻醉大鼠舌头受到有害热刺激（54摄氏度）和化学刺激（1M戊酸）时，三叉神经尾侧亚核背内侧浅层（Vc）单个神经元的反应。然后我们记录了对辣椒素（330微摩尔）或尼古丁（0.6M）的反应，刺激方式为单次、以1分钟ISI重复施加或持续恒流施加。在首次施加辣椒素并经过一段休息期后，以相同方式重新施加辣椒素以测试SIR。14个Vc神经元对依次施加戊酸的平均反应在各试验中无显著变化，表明不存在快速耐受或致敏。11个Vc神经元对反复施加辣椒素的平均反应在前八次试验中显著增加，然后趋于平稳。在休息期后，自发放电恢复到施加辣椒素前的水平。重新施加辣椒素后，平均反应在显著延迟后（由于脱敏）再次增加，但未恢复到初始系列中达到的峰值放电率（部分SIR）。恒流施加辣椒素会诱发相同的致敏，随后几乎完全恢复到SIR。单次施加辣椒素会使另外八个神经元的放电显著增加，但与重复或恒流施加辣椒素相比，增加速率和最大放电率均低得多。在休息期后再次施加一次辣椒素时，放电率没有变化，表明不存在SIR。这些结果表明，维持辣椒素浓度会导致神经元反应逐渐增加，这与致敏过程相似。反复施加辣椒素时，脱敏可被克服，从而导致Vc反应延迟恢复，类似于SIR。相比之下，17个Vc神经元对反复或恒流施加尼古丁的平均反应仅在最初3分钟内增加，然后即使在仍在施加尼古丁时也降至自发放电水平。这些结果与人类依次施加尼古丁时所感知的刺激减少相一致。
