Sensitization, desensitization and stimulus-induced recovery of trigeminalneuronal responses to oral capsaicin and nicotine

Repeated application of capsaicin at a 1-min interstimulus interval (ISI) t o the tongue induces a progressively increasing irritant sensation (sensiti zation), followed after a rest period by reduced sensitivity to further cap saicin (desensitization). Sequential reapplication of capsaicin induces irr itation that eventually increases to initial levels: stimulus-induced recov ery (SIR). In contrast, repeated application of nicotine elicits a declinin g irritant sensation across trials. To investigate possible neural correlat es of these phenomena, we recorded from single units in superficial laminae of the dorsomedial trigeminal subnucleus caudalis (Vc) that responded to n oxious thermal (54 degrees C) and chemical (1 M pentanoic acid) stimulation of the tongue of anesthetized rats. We then recorded responses to either c apsaicin (330 mu M) 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 app lication of pentanoic acid did not vary significantly across trials, indica ting 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 h ad returned to the precapsaicin level. With capsaicin reapplication, the av eraged response increased again after a significant delay (due to desensiti zation), but did not reattain the peak firing rate achieved in the initial series (partial SIR). Constant-flow application of capsaicin induced an ide ntical 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 wit h repetitive or constant-flow capsaicin. When capsaicin was reapplied once after the rest period, there was no change in firing rate indicating absenc e of SIR. These results indicate that maintenance of the capsaicin concentr ation induces a progressive increase in neuronal response that parallels se nsitization. With recurrent capsaicin application, desensitization can be o vercome 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 decr eased to spontaneous levels even as nicotine was still being applied. These results are consistent with the decrease in the perceived irritation elici ted by sequential application of nicotine in humans.