Linda C. Lundblad

Activation of the cortical pain network by soft tactile stimulation after injection of sumatriptan.

Abstract The anti‐migraine drug sumatriptan often induces unpleasant somatosensory side effects, including a dislike of being touched. With a double‐blind cross‐over design, we studied the effects of sumatriptan and saline on perception (visual analogue scale) and cortical processing (functional magnetic resonance imaging) of tactile stimulation in healthy subjects. Soft brush stroking on the calf (n = 6) was less pleasant (p < 0.04) and evoked less activation of posterior insular cortex in the sumatriptan compared to the saline condition. Soft brushing activated pain processing regions (anterior insular, lateral orbitofrontal, and anterior cingulate cortices, and medial thalamus) only in the sumatriptan condition, whereas activation of somatosensory cortices was similar in both conditions. Soft brush stroking on the palm (n = 6) was equally pleasant in both conditions. One possible mechanism for the activation of pain processing regions by brush stroking is sensitization of nociceptors by sumatriptan. Another possibility is inhibition of a recently discovered system of low‐threshold unmyelinated tactile (CT) afferents that are present in hairy skin only, project to posterior insular cortex, and serve affective aspects of tactile sensation. An inhibition of impulse transmission in the CT system by sumatriptan could disinhibit nociceptive signalling and make light touch less pleasant. This latter alternative is consistent with the observed reduction in posterior insular cortex activation and the selective effects of stimulation on hairy compared to glabrous skin, which are not explained by the nociceptor sensitization account.

Sumatriptan (5-HT1B/1D-agonist) causes a transient allodynia.

Unpleasant sensory symptoms are commonly reported in association with the use of 5-HT1B/1D-agonists, i.e. triptans. In particular, pain/pressure symptoms from the chest and neck have restricted the use of triptans in the acute treatment of migraine. The cause of these triptan induced side-effects is still unidentified. We have now tested the hypothesis that sumatriptan influences the perception of tactile and thermal stimuli in humans in a randomized, double-blind, placebo-controlled cross-over study. Two groups were tested; one consisted of 12 (mean age 41.2 years, 10 women) subjects with migraine and a history of cutaneous allodynia in association with sumatriptan treatment. Twelve healthy subjects (mean age 38.7 years, 10 women) without migraine served as control group. During pain- and medication-free intervals tactile directional sensibility, perception of dynamic touch (brush) and thermal sensory and pain thresholds were studied on the dorsal side of the left hand. Measurements were performed before, 20, and 40 min after injection of 6 mg sumatriptan or saline. Twenty minutes after injection, sumatriptan caused a significant placebo-subtracted increase in brush-evoked feeling of unpleasantness in both groups (P < 0.01), an increase in brush-evoked pain in migraineurs only (P = 0.021), a reduction of heat pain threshold in all participants pooled (P = 0.031), and a reduction of cold pain threshold in controls only (P = 0.013). At 40 min after injection, no differences remained significant. There were no changes in ratings of brush intensity, tactile directional sensibility or cold or warm sensation thresholds. Thus, sumatriptan may cause a short-lasting allodynia in response to light dynamic touch and a reduction of heat and cold pain thresholds. This could explain at least some of the temporary sensory side-effects of triptans and warrants consideration in the interpretation of studies on migraine-induced allodynia.

Slow brushing reduces heat pain in humans

C‐tactile (CT) afferents are unmyelinated low‐threshold mechanoreceptors optimized for signalling affective, gentle touch. In three separate psychophysical experiments, we examined the contribution of CT afferents to pain modulation.

Cortical processing of tactile direction discrimination based on spatiotemporal cues in man

Tactile direction discrimination (TDD), the ability to determine the direction of an objects movement across the skin, is used clinically to detect and quantify tactile dysfunction. We have previously identified a cortical network for TDD based on skin stretch information that includes the second somatosensory, anterior insular and dorsolateral prefrontal cortices. In the present study we investigated cortical processing of TDD based on spatiotemporal cues. Sixteen healthy subjects (8 females; mean age, 25.5 years; range, 23-32 years) were stimulated with a low-friction, spatiotemporal rolling wheel on the right thigh during functional magnetic resonance imaging (fMRI). The subjects were instructed to indicate the distal or proximal rolling direction of the stimulus. The fMRI contrast between rolling wheel stimulation and rest showed activations in several areas which included the left (contralateral) primary somatosensory, bilateral second somatosensory, bilateral anterior insular, and bilateral dorsolateral prefrontal cortices. We conclude that, spatiotemporal TDD is processed in a largely similar distributed cortical network as skin stretch TDD. Further, spatiotemporal TDD activated primary somatosensory cortex whereas a role for this area in processing of skin stretch TDD has not been demonstrated.

Tactile direction discrimination and vibration detection in diabetic neuropathy

Löken LS, Lundblad LC, Elam M, Olausson HW. Tactile direction discrimination and vibration detection in diabetic neuropathy. Acta Neurol Scand: 2010: 121: 302–308.
© 2009 The Authors Journal compilation

Processing in prefrontal cortex underlies tactile direction discrimination: An fMRI study of a patient with a traumatic spinal cord lesion.

We have investigated cortical processing of tactile direction discrimination (TDD) in a patient with unilateral tactile disturbance due to spinal cord lesion. The patient R.A. (male, 45 years old), suffers from a traumatic dorsal column lesion at the level of Th XI-XII on the right side. He was instructed to report the direction of 2mm long skin pull stimulations applied in a proximal or distal direction on his right or left lower legs during functional magnetic resonance imaging (fMRI). Although R.A. considered himself to have nearly normal tactile sensibility, testing showed severely disturbed TDD on his right leg whereas results were within the range of healthy subjects on his left leg. For both legs TDD activated an extensive cortical network that included opercular parietal area 1 (OP1) of the second somatosensory cortex (S2), as has previously been observed in healthy subjects. However, dorsolateral prefrontal cortex (DLPFC) and anterior insular cortex (AIC) were only activated for the unaffected (left) leg where TDD was normal. A revisit of previously published data showed that healthy subjects consistently had TDD-related activations in DLPFC and AIC. However, in several healthy subjects AIC, but not DLPFC, was also activated for skin pull stimulations per se without the TDD task. Thus, the patients data, in conjunction with the previous results from healthy subjects, suggest that DLPFC processing is important for tactile decision making based on proper tactile input.

Sympathetic Nerve Activity in Monozygotic TwinsNovelty and Significance: Identical at Rest but Not During Arousal

Microneurographic recordings of human muscle sympathetic nerve activity responses to sudden sensory stimuli (ie, arousal) have revealed 2 intraindividually reproducible response profiles in healthy young males that predict different neural and blood pressure responses to more sustained stress. Approximately 50% of subjects inhibit muscle sympathetic nerve activity during arousal, whereas the remaining 50% do not, and the latter group displays a markedly greater blood pressure increase in response to arousal, as well as during and after 3 minutes of mental arithmetic. Studying a group of monozygotic twins (10 pairs, 2 excluded from analysis), the aim of the present study was to evaluate the degree of genetic determination of these sympathetic response profiles. Muscle sympathetic burst incidence at rest was similar in twins, with a within-pair burst incidence ratio of 0.87±0.02 (SEM) compared with 0.73±0.07 found in unrelated pairs (P=0.002), confirming a previous study from our laboratory. In contrast, the sympathetic responses to arousal showed large twin within-pair variance (arousal inhibition ratio 0.56±0.11), which did not significantly differ (P=0.939) from the variance in pairs of unrelated subjects (0.46±0.11). The finding that human muscle sympathetic nerve responses to arousal are less determined by genotype than the resting level of corresponding sympathetic nerve activity suggests that the arousal response pattern is more prone to be altered by environmental factors. This raises the possibility that these intraindividually reproducible sympathetic neural response profiles can be modified in a positive direction from a cardiovascular risk perspective.

FC12.1 Quantification of mild diabetic neuropathy

world’ topography (characterized by strong local clustering in combination with short path lengths) are known to facilitate synchronization, and possibly seizure generation. Objective: We tested the hypothesis that real brain networks during seizures display small-world features, using intracerebral recordings of mesial temporal lobe seizures. Methods: We used the synchronization likelihood (SL) as a measure of functional correlation in the intracerebral EEG recordings of 7 patients with mesial temporal lobe epilepsy (MTLE). The signals were analyzed in different frequency bands. After correction for the differences in synchronization in the periods, the cluster coefficient C and the path length L were computed for 5 periods of interest. These periods were: interictal, before-, duringand after rapid discharges (resp. BRD, DRD and ARD) (in which the periods DRD and ARD are ictal and BRD is seen as preictal) and postictal. Results: The neuronal network changed during seizure activity, with an increase of C most prominent in the lower frequencies (1–13 Hz) at the end and after the seizure and shortening of L at the end of the seizure (4–8 Hz), expanding after the seizure to 4–13 Hz. Conclusions: During MTLE seizures the neuronal network changes towards a small-world configuration compared to the interictal network, even after correcting for changes in synchronization strength. The interictal network has characteristics of a random network. Analysis of neuronal networks during seizures may provide insight into seizure genesis and development.