Abstract
Dear Sir I appreciated very much the interest of Leon-Sarmiento and his colleagues in our studies on blink reflex in migraine. In addition, their questions about our recent study (1) may be easily resolved: our aim was to detect the diffuse noxious inhibitory control (DNIC) effects on R2 component, avoiding the recording of R3, for the following reasons:
We aimed to replicate the experimental design previously employed by Ellrich and Treede (2). As in that study, the 10-s interstimuli interval (ISI) was chosen to ‘avoid a R3 component and a habituation of the R2’ (2).
The R3 component is not nociceptive in origin, as indicated by several pieces of evidence (3), so it is not a suitable method to test trigeminal nociception, as well as R2. It is an ultralate response, strongly dependent on attention, with mixed nociceptive and not nociceptive afferents (3). The R3 abnormalities detected in migraine may be ascribed to a general dysfunction of adaptation capacity to environmental conditions, as clearly expressed in our previous report (4), and not to a specific disturbance of trigeminal nociception. In the BR example reported in the cited fig. 3 (1), no R3 is evident, unless we have to consider the R3 as the final part of the R2, and not an independent component. In this case, the hypothesis of a common origin may be even more reliable.
The influence of supra-segmental control is more evident for the R3 than the R2 component. In our recent study (1), the cognitive modulation of a multisynaptic response as the R2 raised the question of whether the lack of its inhibition by the contemporary remote pain was due to the failure of DNIC control at the brainstem level or to altered modulation of attention towards trigeminal stimuli, as suggested by other studies on laser-evoked potentials in chronic migraine (5). Including the R3 evaluation might have reinforced the latter hypothesis, without excluding the former. In other words, the effects of DNIC on R3 might not have added further data to the present ones, probably inducing additional methodological problems.
The easy habituation of R3 might have significantly prolonged the experimental trial, each series exceeding at least four times the length provided in the present study. In addition, the stimulus intensity should have been settled above the pain threshold, to ensure R3 recording in migraine and controls. These additional methodological adjustments should have prolonged and complicated the procedure, without further supporting the fundamental issue of the DNIC function in migraine.
Furthermore, R3 evaluation was not considered fundamental in the assessment of trigeminal pain threshold in both episodic and chronic migraine patients: the electrical pain threshold was well established in patients and controls, and it was not dissimilar across groups. Conversely, pain induced by capsaicin on the dorsum of the hand was more strongly perceived in chronic migraine, in respect of episodic migraine and controls. This phenomenon was attributed to a diffuse hyperalgesia, probably caused by dysfunction of pain control at the central level occurring in chronic migraine. Its origin is not comparable to the local hyperalgesia found in burning mouth syndrome, which was recently recognized as a neuropathic pain (6).
Finally, I wish to remark that, except for some very specific experimental paradigms like that employed in our recent study (1), it seems better to test pain and nociception by the employment of reflexes and evoked responses, subtended by purely nociceptive afferent stimulation, rather than by laser or specific electrical devices.