Abnormal cortical pain processing in patients with cardiac syndrome X.

AIMS: Previous studies suggested that an enhanced pain sensitivity is present in patients with cardiac syndrome X (SX). We investigated whether SX patients present abnormalities in the electrical cerebral signals generated by pain stimuli. METHODS AND RESULTS: Cortical laser evoked potentials (LEPs) were recorded in 16 SX patients, in 10 patients with refractory angina due to obstructive coronary artery disease (CAD) and in 13 healthy controls. LEPs were recorded during stimulation of chest and right hand dorsum. Three sequences of painful stimuli were applied at each site. Subjective pain rating was assessed by a 0-100 mm visual analogic scale (VAS). Basal LEPs did not differ among groups and there were no differences for most LEP components across the repetitions of stimuli. However, the amplitude of the N2/P2 LEP component, specifically reflecting cortical pain processing, decreased across the three sequences of stimuli in controls and CAD patients, but not in SX patients. Compared with the first sequence, the N2/P2 amplitude during the third sequence of stimuli in the three groups was 77+/-16, 56+/-24, and 99+/-34%, respectively, for chest (P=0.001), and 63+/-31, 72+/-17, and 98+/-46%, respectively, for right hand (P=0.03) stimulation. The changes in VAS pain score across the three sequences paralleled those of N2/P2 amplitude. CONCLUSION: Our data show that in SX patients, central handling of painful stimuli is characterized by inadequate habituation, which might play a role in determining the peculiar clinical characteristics of anginal chest pain of these patients.

Inhibitory effect of capsaicin evoked trigeminal pain on warmth sensation and warmth evoked potentials.

The aim of the study was to evaluate the effect of tonic pain evoked by topical application of capsaicin on the somatosensory sensation of warmth. The warmth pathways were studied in ten healthy subjects by recording the scalp potentials evoked by non-painful warm laser stimuli delivered on both the right and left perioral region (warmth C-fiber related laser-evoked potentials (C-LEPs)). Tonic pain was induced by topical capsaicin application above the lateral part of the right upper lip. The area of primary and secondary hyperalgesia were mapped. C-LEPs were obtained from 31 scalp electrodes before, during, and after capsaicin application. C-LEPs from the right perioral region were evoked by laser stimuli delivered to the area of secondary hyperalgesia during capsaicin application and on both the areas of primary and secondary hyperalgesia after capsaicin removal. While the lateralized N1/P1 component (around 185 ms of latency) was not affected by the capsaicin, the amplitudes of the later vertex C-LEPs (around 260 and 410 ms of latency for the N2a and P2 potentials, respectively) evoked from the secondary hyperalgesic area on the right side and from a symmetrical non-hyperalgesic area on the left perioral region were significantly decreased during capsaicin application and after capsaicin removal, as compared with the baseline recordings. At the same times, the rating of the laser-evoked warmth sensation was reduced significantly. This inhibitory effect can occur at brainstem level and is possibly due to: 1) trigemino-cortico-trigeminal circuits, similar to those mediating the classical diffuse noxious inhibitory control, or 2) an increased background activity of the capsaicin-insensitive A-fibers, which mediate the secondary hyperalgesia. Probably due to a peripheral inhibitory mechanism, neither reliable C-LEP components nor warmth sensation were evoked by laser pulses delivered to the primary hyperalgesic area. This is the first neurophysiological evidence in humans of an inhibitory effect of pain on warmth sensation.

Functional assessment of A delta and C fibers in patients with Fabry's disease.

The pathophysiology of neuropathic pain in Fabry's disease (FD) is still largely unknown. Seven FD patients were studied by laser evoked potentials (LEPs) to assess the function of the A delta and C fibers. Laser pulses were delivered on the skin of the hand and perioral region at painful intensity to record LEPs related to A delta-fiber inputs and at nonpainful intensity to obtain LEPs related to C-fiber inputs. When the perioral region was stimulated, a vertex positive component was recorded with a mean latency of 260.3 ms and 376 ms after A delta- and C-fiber stimulation, respectively. The mean A delta-LEP amplitude was significantly lower in FD patients (N1/P1 mean values were 2.8 microV and 4.5 microV after hand and face stimulation, respectively, compared to 4 microV and 8.9 microV for controls; N2/P2 mean values were 8.2 microV and 11.1 microV after hand and face stimulation, respectively, and 16.7 microV and 22.3 microV in controls). Unlike the healthy subjects, 6 FD patients, suffering from neuropathic pain, showed a late positive potential related to C-fiber function (mean latency, 377.1 ms) also after facial stimulation at painful intensity, suggesting a relative overflow of C-fiber input, which may be relevant in the pathophysiology of pain in this disease.

Influence of modafinil on somatosensory input processing in the human brain-stem.

OBJECTIVE: Since high frequency oscillations (HFOs) evoked by upper limb stimulation are susceptible to arousal fluctuation, we verified whether administration of modafinil, a vigilance promoting drug, modifies such responses at different levels of the somatosensory system. METHODS: HFOs were obtained in 6 healthy volunteers by 500-700 Hz filtering of right median nerve somatosensory evoked potentials, before and 2 hours after the administration of 100 mg modafinil. Raw data were further submitted to brain electrical source analysis. RESULTS: Modafinil significantly increased subcortical HFOs, as well as the strength of a dipolar source at the base of the skull. CONCLUSIONS: Our data suggest that modafinil exerts its action also at the level of the brain-stem, where it interferes with the processing of somatosensory ascending inputs.

Short-term plastic changes of the human nociceptive system following acute pain induced by capsaicin.

OBJECTIVE: To investigate possible neuroplastic changes induced by pain in cerebral areas devoted to nociceptive input processing. METHODS: CO(2) laser-evoked potentials (LEPs) were recorded from 10 healthy subjects after stimulation of the right and left hand dorsum. Acute pain was obtained by topical application of capsaicin on the skin of right hand dorsum. LEPs were recorded after right and left hand stimulation before capsaicin, at the peak pain and 10-20 min after capsaicin removal. Right hand LEPs were evoked by laser stimuli delivered over the zone of secondary hyperalgesia during capsaicin and on both the zones of primary and secondary hyperalgesia after capsaicin removal. RESULTS: After right hand stimulation, the vertex LEPs, which are generated in the cingulate cortex, were significantly decreased in amplitude during capsaicin application and after capsaicin removal. Moreover, the topography of these potentials was modified after capsaicin removal, shifting from the central toward the parietal region. Dipolar modelling showed that the dipolar source in the anterior cingulate cortex moved backward after capsaicin removal. All these changes were not observed after stimulation of the left hand, contralateral to the application of capsaicin, thus suggesting that functional changes are selective for the painful skin and the adjacent territories. CONCLUSIONS: Our results suggest that acute cutaneous pain may inhibit the neural activity in regions of central nervous system processing nociceptive inputs and cortical representation of these inputs can be rapidly modified in presence of acute pain.

Attention-related modifications of ultra-late CO(2) laser evoked potentials to human trigeminal nerve stimulation.

Our study aimed at investigating the scalp topography of ultra-late CO(2) laser evoked potentials (LEPs), which are related to C fiber activation, and at exploring the effect of attention deviation on ultra-late LEPs. Brain responses to non-painful CO(2) laser stimuli were recorded in ten healthy subjects in three different conditions: (i) neutral condition in which subjects did not have any task; (ii) distraction condition in which subjects were asked to perform a mathematical task; and (iii) attention condition in which subjects had to count the number of stimuli. In all subjects, also A fiber-related late LEPs were recorded after painful CO(2) laser stimulation. The ultra-late LEPs in attention condition included an earlier negative potential (ultra-late N1) in the contralateral temporal region and a simultaneous frontal positive response (ultra-late P1). Later, a vertex biphasic component (ultra-late N2a and ultra-late P2) was identifiable. The vertex ultra-late LEP amplitude was significantly decreased in both neutral and distraction condition. Ultra-late LEPs showed a longer latency than late LEPs, but the scalp distributions of both ultra-late and late LEPs were very similar, thus suggesting that the same cerebral areas may be involved in their generation. Since attention deviations have a strong effect on ultra-late LEP amplitude, the subject's attention should be addressed to CO(2) laser stimuli when ultra-late LEPs are used for clinical purposes.