1. Properties of sensory receptors with slowly conducting nerve fibers (less than 10 m/s) were studied using a rat skin-saphenous nerve in vitro preparation where receptive fields of identified single units can be isolated and superfused at the corium side with defined chemical solutions. 2. With mechanical search stimuli, 150 slowly adapting units were identified, 88% C-fibers, and the remainder, A delta-fibers. The majority of these units (65%) were categorized as mechano-heat sensitive ("polymodal") with controlled radiant heat stimulation. The remaining units were classified as low- or high-threshold mechanoreceptors according to their von Frey thresholds. 3. Bradykinin (BK), in concentrations of 10(-8) to 10(-4) M, was repeatedly applied for 1 min at 10-min intervals. Fifty-six percent of the polymodal C-fibers responded to BK (up to 10(-5) M), in contrast to 17% of the heat-insensitive units (P less than 0.01). No correlation between BK sensitivity and conduction velocity or von Frey threshold was found. 4. The BK "threshold concentrations" to excite C- and A delta-fibers were about equally distributed over a range from 10(-8) to 10(-5) M. 5. There was a large interindividual variability in pattern and magnitude of the response to BK. Intraindividually, a marked tachyphylaxis upon repeated BK stimulation was observed. 6. In fibers with a slow development of tachyphylaxis, the effects of conditioning application of different chemicals on BK responsiveness were studied. Norepinephrine in 10(-7) M concentration did not produce a significant effect, whereas 10(-5) M and 10(-4) M seemed to increase the BK responses. 7. Prostaglandin E2 (10(-6) M) caused a weak sensitization to BK on average (n.s.), but serotonin (10(-6) M) was clearly effective (P less than 0.05). 8. The strongest sensitization to BK (P = 0.01) resulted from conditioning heat stimulation, which also uncovered a responsiveness in some units initially insensitive to BK. 9. In some experiments the calcium concentration in the superfusate of receptive fields was lowered to 0.3 mM, which induced ongoing activity in C-fibers and markedly increased the BK responses in two polymodal units tested. Increasing the calcium concentration to 3.0 mM reversed these effects. 10. After completing the BK test protocol, polymodal C-fibers were exposed to other chemicals.(ABSTRACT TRUNCATED AT 400 WORDS)

Visual information is conducted by two parallel pathways (luminance- and contour-processing pathways) which are thought to be differentially affected in migraine and can be investigated by means of pattern-reversal visual evoked potentials (VEPs). Components and habituation of VEPs at four spatial frequencies were compared between 26 migraineurs (13 without aura, MO; 13 with aura, MA) and 28 healthy volunteers. Migraineurs were recorded in the headache-free interval (at least 72 h before and after an attack). Five blocks of 50 responses to chequerboards of 0.5, 1, 2 and 4 cycles per degree (c.p.d.) were sequentially averaged and analysed for latency and amplitude. Differences in VEPs were dependent on spatial frequency. Only when small checks were presented, i.e. at high spatial frequency (2 and 4 c.p.d.), was the latency of N2 significantly prolonged in MA and did it tend to be delayed in MO subjects. Habituation behaviour was not significantly different between groups under the stimulating conditions employed. Prolonged N2 latency might be explained by the lack or attenuation of a contour-specific component N130 in migraineurs, indicating an imbalance of the two visual pathways with relative predominance of the luminance-processing Y system. These results reflect an interictally persisting dysfunction of precortical visual processing which might be relevant in the pathophysiology of migraine.

Intensive multidisciplinary headache treatment is highly effective for patients with chronic headaches. Furthermore, migraine symptomatology responds especially well to this intensive treatment program, whereas effects on tension-type headaches were realized by both multidisciplinary programs. Randomized controlled trials and subgroup analysis are needed to find out if these results can be replicated and which patient characteristics allow for sufficient improvements for headache sufferers even with less complex treatment.

Clinical findings and recent non-invasive functional imaging studies pinpoint the insular cortex as the crucial brain area involved in cold sensation. By contrast, the role of primary (SI) and secondary (SII) somatosensory cortices in central processing of cold is controversial. So far, temporal activation patterns of cortical areas involved in cold processing have not been examined. Using magnetoencephalography, we studied, in seven healthy subjects, the temporo-spatial dynamics of brain processes evoked by innocuous and noxious cold stimulation as compared to tactile stimuli. For this purpose, a newly designed and magnetically silent cold-stimulator was employed. In separate runs, cold and painful cold stimuli were delivered to the dorsum of the right hand. Tactile afferents were stimulated by pneumatic tactile stimulation.Following innocuous cold stimulation (DeltaT=5+/-0.3 degrees C in 50+/-2ms), magnetic source imaging revealed an exclusive activation of the contra- and ipsilateral posterior insular cortex. The mean peak latencies were 194.3+/-38.1 and 241.0+/-31.7ms for the response in the ipsi- and contralateral insular cortex, respectively. Based on the measurement of onset latencies, the estimated conduction velocity of peripheral nerve fibres mediating cold fell in the range of Adelta-fibres (7.4+/-0.8 m/s). Noxious cold stimulation (DeltaT=35+/-5 degrees C in 70+/-12ms) initially activated the contra- and ipsilateral insular cortices in the same latency ranges as innocuous cold stimuli. Additionally, we found an activation of the contra- and ipsilateral SII areas (peak latencies 304+/-22.7 and 310.1+/-19.4ms, respectively) and a variable activation of the cingulate cortex. Notably, neither cold- nor painful cold stimulation produced an activation of SI. By contrast, the evoked cortical responses following tactile stimulation could be located to the contralateral SI cortex and bilateral SII. In conclusion, this study strongly corroborates the posterior insular cortex as the primary somatosensory area for cortical processing of cold sensation. Furthermore, it supports the role of SII and the cingulate cortex in mediating freeze-pain. Therefore, these results suggest different processing of cold, freeze-pain and touch in the human brain.

The excitability of the cerebral cortex in the interictal state of migraine appears to be fundamental in the brain's susceptibility to migraine attacks. Subpopulations of cortical neurons are reported to have different physiological response properties to different interstimulus intervals (ISIs) and, hence, may be differentially altered or modulated in migraine. The aim of this study therefore was to evaluate response characteristics of temporally and spatially defined neuronal subpopulations in the cortex of migraineurs. To this end, we measured, by means of magnetoencephalography (37-channel neuromagnetometer), the response properties of the early components of the somatosensory evoked magnetic fields following electrical stimulation of the median nerve, the N20m and P35m, at ISIs ranging between 0.3 and 6 s. As a measure of the number of excited neurons underlying the N20m and P35m, we evaluated the root mean square (r.m.s.) of the deflections across all 37 channels at the corresponding latencies and the corresponding dipole moment of the equivalent current dipole (ECD strength). Twenty consecutive women with at least three migraine attacks/month (range 3-8/month) fulfilling the International Headache Society criteria and 20 age-matched healthy women were included in the study. In migraineurs, the r.m.s. and ECD strength of N20m was increased at all ISIs (r.m.s., P < 0.05; ECD strength, P < 0.01) and positively related to the mean attack frequency (r.m.s., R(s) = 0.6, P < 0.01; ECD strength, R(s) = 0.5, P < 0.05). In contrast, the r.m.s. and ECD strength of P35m did not differ significantly between migraineurs and control subjects and did not correlate significantly with the frequency of migraine attacks. Responses to different ISIs did not differ significantly between migraineurs and control subjects. The r.m.s. of N20m was stable for ISIs between 0.5 and 6 s and decreased significantly at an ISI of 0.3 s. In contrast, the r.m.s. of P35m decreased continuously as the ISI was decreased below 6 s and this reached significance for an ISI of < or =1 s. Habituation of N20m or P35m, i.e. a decrease in response magnitude following repetitive stimulation over time, was not found in either the control subjects or in the migraineurs. It is concluded that the population of neurons in the primary somatosensory cortex underlying the N20m are hyperexcitable and that this hyperexcitability is linked to the frequency of migraine attacks. This hyperexcitability appears not to be related to habituation since habituation was not found in the control subjects. In contrast, the magnitude of P35m is not pathophysiologically linked to the interictal state of migraine. Furthermore, the cellular mechanisms causing ISI-dependent depression of N20m and P35m are not altered in migraine.