Clinical and Experimental Hypertension, Mar 14, 2019
Background: The impact of renal denervation (RDN) on muscle sympathetic nerve activity (MSNA) at ... more Background: The impact of renal denervation (RDN) on muscle sympathetic nerve activity (MSNA) at rest remains controversial. Mental stress (MS) induces transient changes in sympathetic nerve activity, heart rate (HR) and blood pressure (BP). It is not known whether RDN modifies these changes. Purpose: The main objective was to assess the effect of RDN on MSNA and BP alterations during MS. Methods: In 14 patients (11 included in analysis) with resistant hypertension multi-unit MSNA, BP (Finometer ®) and HR were assessed at rest and during forced arithmetics at baseline and 6 months after RDN. Results: Systolic office BP decreased significantly 6 months after RDN (185 ± 29 vs.175 ± 33 mmHG; p = 0.04). No significant changes in MSNA at rest (68 ± 5 vs 73 ± 5 bursts/100hb; p = 0.43) were noted and no significant stress-induced change in group averaged sympathetic activity was found pre-(101 ± 24%; p = 0.9) or post-intervention (108 ± 26%; p = 0.37). Stress was associated with significant increases in mean arterial BP (p < 0.01) and HR (p < 0.01) at baseline, reactions which remained unaltered after intervention. We did not note any correlation between sympathetic nerve activity and BP changes after RDN. Conclusion: Thus, in our group of resistant hypertensives we find no support for the hypothesis that the BP-lowering effect of RDN depends on altered neurovascular responses to stress.
An individual's blood pressure (BP) reactivity to stress is linked to increased risk of hypertens... more An individual's blood pressure (BP) reactivity to stress is linked to increased risk of hypertension and cardiovascular disease. However, inter-and intra-individual BP variability makes understanding the coupling between stress, BP reactivity, and long-term outcomes challenging. Previous microneurographic studies of sympathetic signaling to muscle vasculature (i.e. muscle sympathetic nerve activity, MSNA) have established a neural predictor for an individual's BP reactivity during shortlasting stress. Unfortunately, this method is invasive, technically demanding, and time-consuming and thus not optimal for widespread use. Potential central nervous system correlates have not been investigated. We used MagnetoEncephaloGraphy and Magnetic Resonance Imaging to search for neural correlates to sympathetic response profiles within the central autonomic network and sensorimotor (Rolandic) regions in 20 healthy young males. The main correlates include (a) Rolandic beta rebound and an anterior cingulate cortex (ACC) response elicited by sudden stimulation and (b) cortical thickness in the ACC. Our findings highlight the involvement of the ACC in reactions to stress entailing peripheral sympathetic responses to environmental stimuli. The Rolandic response furthermore indicates a surprisingly strong link between somatosensory and autonomic processes. Our results thus demonstrate the potential in using non-invasive neuroimaging-based measures of stress-related MSNA reactions, previously assessed only using invasive microneurography. Cardiovascular disease is the leading cause of death worldwide and high blood pressure (BP) is the most important risk factor for global disease burden 1. Approximately half of all cases are diagnosed with essential hypertension for which there is no unifying explanation. So far, while epidemiological research has identified many risk factors, it has been difficult to develop useful individual profiles for the management of hypertension, from prediction and early diagnosis to personalized treatment. Furthermore, clinical trials of anti-hypertensive medication have relied on large patient groups, mostly considered to be homogenous regarding their condition. Thus, understanding of specific disease mechanisms for essential hypertension, and related tools for research and clinical use, are still lacking. There is, however, evidence from large-scale longitudinal studies indicating that environmental stress is an important risk factor for essential hypertension 2,3. Neural regulation is thus likely to be of importance. Acute stress is often triggered by a sudden stimulus (e.g., a car honking, or an unexpected notification on a mobile) initiating a defense reaction. This transitory response often includes increases in heart rate, BP, and
Unpleasant sensory symptoms are commonly reported in association with the use of 5-HT 1B/1D-agoni... more Unpleasant sensory symptoms are commonly reported in association with the use of 5-HT 1B/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, placebocontrolled 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 brushevoked feeling of unpleasantness in both groups (P < 0.01), an increase in brushevoked 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. ᮀ Allodynia, hyperalgesia, migraine, sensory thresholds, triptans
Most of the studies aiming to investigate the human tactile sense are done on the glabrous skin. ... more Most of the studies aiming to investigate the human tactile sense are done on the glabrous skin. Still, there is a need for a quantitative method for evaluating nervous function of the hairy skin. Tactile direction discrimination, the ability to determine the direction of movement across the skin provides a clinical method to quantify tactile function of the hairy skin in humans. The method is easy-to-use, rapid, and inexpensive but has not been compared to vibration detection which is considered as the standard method for psychophysical examination of peripheral neuropathy. The peripheral neural mechanisms for tactile direction discrimination have been extensively studied, as well as the ascending pathways in the spinal cord. Nevertheless, the supraspinal mechanisms are imperfectly known. In this study we have compared the clinical test for tactile direction discrimination with vibration detection in a group of patients with diabetic neuropathy. We have also thoroughly studied the cortical processing of tactile direction discrimination. The results are presented in four separate papers. The results showed that the clinical test for tactile direction discrimination had similar sensitivity as vibration detection in detecting patients with diabetic neuropathy. The cortical network for tactile direction discrimination involved the primary somatosensory cortex, the opercular parietal area 1 of the secondary somatosensory cortex, and dorsolateral prefrontal cortex as well as anterior insular cortex. In conclusion, the clinical test for tactile direction discrimination provides a quantitative clinical test that is sensitive in detecting peripheral nervous lesions. The test seems well-suited for following patients with disturbances in the peripheral and central nervous systems. The neurophysiological mechanisms underlying tactile direction discrimination are well studied from the peripheral afferents in the skin, through the spinal cord and to information processing in the brain.
Sudden, unexpected stimuli can induce a transient inhibition of sympathetic vasoconstriction to s... more Sudden, unexpected stimuli can induce a transient inhibition of sympathetic vasoconstriction to skeletal muscle, indicating a link to defense reactions. This phenomenon is relatively stable within, but differs between, individuals. It correlates with blood pressure reactivity which is associated with cardiovascular risk. Inhibition of muscle sympathetic nerve activity (MSNA) is currently characterized through invasive microneurography in peripheral nerves. We recently reported that brain neural oscillatory power in the beta spectrum (beta rebound) recorded with magnetoencephalography (MEG) correlated closely with stimulus-induced MSNA inhibition. Aiming for a clinically more available surrogate variable reflecting MSNA inhibition, we investigated whether a similar approach with electroencephalography (EEG) can accurately gauge stimulus-induced beta rebound. We found that beta rebound shows similar tendencies to correlate with MSNA inhibition, but these EEG data lack the robustness o...
An individual’s blood pressure (BP) reactivity to stress is linked to increased risk of hypertens... more An individual’s blood pressure (BP) reactivity to stress is linked to increased risk of hypertension and cardiovascular disease. However, inter- and intra-individual BP variability makes understanding the coupling between stress, BP reactivity, and long-term outcomes challenging. Previous microneurographic studies of sympathetic signaling to muscle vasculature (i.e. muscle sympathetic nerve activity, MSNA) have established a neural predictor for an individual’s BP reactivity during short-lasting stress. Unfortunately, this method is invasive, technically demanding, and time-consuming and thus not optimal for widespread use. Potential central nervous system correlates have not been investigated. We used MagnetoEncephaloGraphy and Magnetic Resonance Imaging to search for neural correlates to sympathetic response profiles within the central autonomic network and sensorimotor (Rolandic) regions in 20 healthy young males. The main correlates include (a) Rolandic beta rebound and an anter...
Sensing movements across the skin surface is a complex task for the tactile sensory system, relyi... more Sensing movements across the skin surface is a complex task for the tactile sensory system, relying on sophisticated cortical processing. Functional MRI has shown that judgements of the direction of tactile stimuli moving across the skin are processed in distributed cortical areas in healthy humans. To further study which brain areas are important for tactile direction discrimination, we performed a lesion study, examining a group of patients with first-time stroke. We measured tactile direction discrimination in 44 patients, bilaterally on the dorsum of the hands and feet, within 2 weeks (acute), and again in 28 patients 3 months after stroke. The 3-month follow-up also included a structural MRI scan for lesion delineation. Fifty-nine healthy participants were examined for normative direction discrimination values. We found abnormal tactile direction discrimination in 29/44 patients in the acute phase, and in 21/28 3 months after stroke. Lesions that included the opercular parietal...
Background: The impact of renal denervation (RDN) on muscle sympathetic nerve activity (MSNA) at ... more Background: The impact of renal denervation (RDN) on muscle sympathetic nerve activity (MSNA) at rest remains controversial. Mental stress (MS) induces transient changes in sympathetic nerve activity, heart rate (HR) and blood pressure (BP). It is not known whether RDN modifies these changes. Purpose: The main objective was to assess the effect of RDN on MSNA and BP alterations during MS. Methods: In 14 patients (11 included in analysis) with resistant hypertension multi-unit MSNA, BP (Finometer ®) and HR were assessed at rest and during forced arithmetics at baseline and 6 months after RDN. Results: Systolic office BP decreased significantly 6 months after RDN (185 ± 29 vs.175 ± 33 mmHG; p = 0.04). No significant changes in MSNA at rest (68 ± 5 vs 73 ± 5 bursts/100hb; p = 0.43) were noted and no significant stress-induced change in group averaged sympathetic activity was found pre-(101 ± 24%; p = 0.9) or post-intervention (108 ± 26%; p = 0.37). Stress was associated with significant increases in mean arterial BP (p < 0.01) and HR (p < 0.01) at baseline, reactions which remained unaltered after intervention. We did not note any correlation between sympathetic nerve activity and BP changes after RDN. Conclusion: Thus, in our group of resistant hypertensives we find no support for the hypothesis that the BP-lowering effect of RDN depends on altered neurovascular responses to stress.
BackgroundC‐tactile (CT) afferents are unmyelinated low‐threshold mechanoreceptors optimized for ... more BackgroundC‐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.MethodsIn total, 44 healthy volunteers experienced heat pain and CT optimal (slow brushing) and CT sub‐optimal (fast brushing or vibration) stimuli. Three different experimental paradigms were used: Concurrent application of heat pain and tactile (slow brushing or vibration) stimulation; Slow brushing, applied for variable duration and intervals, preceding heat pain; Slow versus fast brushing preceding heat pain.ResultsSlow brushing was effective in reducing pain, whereas fast brushing or vibration was not. The reduction in pain was significant not only when the CT optimal touch was applied simultaneously with the painful stimulus but also when the two stimuli were separated in time. For subsequent stimulation, the pain reduction was more prono...
Microneurographic recordings of human muscle sympathetic nerve activity responses to sudden senso... more 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 la...
The anti-migraine drug sumatriptan often induces unpleasant somatosensory side effects, including... more 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&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;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.
We have investigated cortical processing of tactile direction discrimination (TDD) in a patient w... more 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 2 mm 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 patient's 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.
Direction discrimination of a moving tactile stimulus requires intact dorsal columns and provides... more Direction discrimination of a moving tactile stimulus requires intact dorsal columns and provides a sensitive clinical test of somatosensory dysfunction. Cortical mechanisms are poorly understood. We have applied tangential skin pulls to the right lower leg during functional magnetic resonance imaging. Healthy subjects judged the direction of the skin pulls (task experiment, n = 7) or received skin pulls passively (no task experiment, n = 8). Second somatosensory cortex (S2) was activated in the task as well as no task experiment, and there was no signiWcant diVerence in cortical activation between the two experiments. Within S2 nearly all subjects had prominent activations in the caudal and superWcial part, i.e., in the opercular parietal (OP) area 1. S1 was activated in only one of the subjects. Thus, S2 and especially OP 1 seems to be important for processing of lateral skin stretch stimulation. The Wnding suggests that a lesion of this area might cause a disturbance in tactile direction discrimination which should be relevant for clinical testing.
Most of the studies aiming to investigate the human tactile sense are done on the glabrous skin. ... more Most of the studies aiming to investigate the human tactile sense are done on the glabrous skin. Still, there is a need for a quantitative method for evaluating nervous function of the hairy skin. Tactile direction discrimination, the ability to determine the direction of movement across the skin provides a clinical method to quantify tactile function of the hairy skin in humans. The method is easy-to-use, rapid, and inexpensive but has not been compared to vibration detection which is considered as the standard method for psychophysical examination of peripheral neuropathy. The peripheral neural mechanisms for tactile direction discrimination have been extensively studied, as well as the ascending pathways in the spinal cord. Nevertheless, the supraspinal mechanisms are imperfectly known. In this study we have compared the clinical test for tactile direction discrimination with vibration detection in a group of patients with diabetic neuropathy. We have also thoroughly studied the cortical processing of tactile direction discrimination. The results are presented in four separate papers. The results showed that the clinical test for tactile direction discrimination had similar sensitivity as vibration detection in detecting patients with diabetic neuropathy. The cortical network for tactile direction discrimination involved the primary somatosensory cortex, the opercular parietal area 1 of the secondary somatosensory cortex, and dorsolateral prefrontal cortex as well as anterior insular cortex. In conclusion, the clinical test for tactile direction discrimination provides a quantitative clinical test that is sensitive in detecting peripheral nervous lesions. The test seems well-suited for following patients with disturbances in the peripheral and central nervous systems. The neurophysiological mechanisms underlying tactile direction discrimination are well studied from the peripheral afferents in the skin, through the spinal cord and to information processing in the brain.
Background: Neuronal networks with a so-called 'smallworld' topography (characterized by strong l... more Background: Neuronal networks with a so-called 'smallworld' 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-, during-and 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.
Unpleasant sensory symptoms are commonly reported in association with the use of 5-HT1B/1D-agonis... more 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. Measurement...
Tactile direction discrimination and vibration detection in diabetic neuropathy Patients Patients... more Tactile direction discrimination and vibration detection in diabetic neuropathy Patients Patients with type 1 diabetes mellitus were recruited from an outpatient clinic. In a first evaluation, the participants were carefully
Clinical and Experimental Hypertension, Mar 14, 2019
Background: The impact of renal denervation (RDN) on muscle sympathetic nerve activity (MSNA) at ... more Background: The impact of renal denervation (RDN) on muscle sympathetic nerve activity (MSNA) at rest remains controversial. Mental stress (MS) induces transient changes in sympathetic nerve activity, heart rate (HR) and blood pressure (BP). It is not known whether RDN modifies these changes. Purpose: The main objective was to assess the effect of RDN on MSNA and BP alterations during MS. Methods: In 14 patients (11 included in analysis) with resistant hypertension multi-unit MSNA, BP (Finometer ®) and HR were assessed at rest and during forced arithmetics at baseline and 6 months after RDN. Results: Systolic office BP decreased significantly 6 months after RDN (185 ± 29 vs.175 ± 33 mmHG; p = 0.04). No significant changes in MSNA at rest (68 ± 5 vs 73 ± 5 bursts/100hb; p = 0.43) were noted and no significant stress-induced change in group averaged sympathetic activity was found pre-(101 ± 24%; p = 0.9) or post-intervention (108 ± 26%; p = 0.37). Stress was associated with significant increases in mean arterial BP (p < 0.01) and HR (p < 0.01) at baseline, reactions which remained unaltered after intervention. We did not note any correlation between sympathetic nerve activity and BP changes after RDN. Conclusion: Thus, in our group of resistant hypertensives we find no support for the hypothesis that the BP-lowering effect of RDN depends on altered neurovascular responses to stress.
An individual's blood pressure (BP) reactivity to stress is linked to increased risk of hypertens... more An individual's blood pressure (BP) reactivity to stress is linked to increased risk of hypertension and cardiovascular disease. However, inter-and intra-individual BP variability makes understanding the coupling between stress, BP reactivity, and long-term outcomes challenging. Previous microneurographic studies of sympathetic signaling to muscle vasculature (i.e. muscle sympathetic nerve activity, MSNA) have established a neural predictor for an individual's BP reactivity during shortlasting stress. Unfortunately, this method is invasive, technically demanding, and time-consuming and thus not optimal for widespread use. Potential central nervous system correlates have not been investigated. We used MagnetoEncephaloGraphy and Magnetic Resonance Imaging to search for neural correlates to sympathetic response profiles within the central autonomic network and sensorimotor (Rolandic) regions in 20 healthy young males. The main correlates include (a) Rolandic beta rebound and an anterior cingulate cortex (ACC) response elicited by sudden stimulation and (b) cortical thickness in the ACC. Our findings highlight the involvement of the ACC in reactions to stress entailing peripheral sympathetic responses to environmental stimuli. The Rolandic response furthermore indicates a surprisingly strong link between somatosensory and autonomic processes. Our results thus demonstrate the potential in using non-invasive neuroimaging-based measures of stress-related MSNA reactions, previously assessed only using invasive microneurography. Cardiovascular disease is the leading cause of death worldwide and high blood pressure (BP) is the most important risk factor for global disease burden 1. Approximately half of all cases are diagnosed with essential hypertension for which there is no unifying explanation. So far, while epidemiological research has identified many risk factors, it has been difficult to develop useful individual profiles for the management of hypertension, from prediction and early diagnosis to personalized treatment. Furthermore, clinical trials of anti-hypertensive medication have relied on large patient groups, mostly considered to be homogenous regarding their condition. Thus, understanding of specific disease mechanisms for essential hypertension, and related tools for research and clinical use, are still lacking. There is, however, evidence from large-scale longitudinal studies indicating that environmental stress is an important risk factor for essential hypertension 2,3. Neural regulation is thus likely to be of importance. Acute stress is often triggered by a sudden stimulus (e.g., a car honking, or an unexpected notification on a mobile) initiating a defense reaction. This transitory response often includes increases in heart rate, BP, and
Unpleasant sensory symptoms are commonly reported in association with the use of 5-HT 1B/1D-agoni... more Unpleasant sensory symptoms are commonly reported in association with the use of 5-HT 1B/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, placebocontrolled 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 brushevoked feeling of unpleasantness in both groups (P < 0.01), an increase in brushevoked 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. ᮀ Allodynia, hyperalgesia, migraine, sensory thresholds, triptans
Most of the studies aiming to investigate the human tactile sense are done on the glabrous skin. ... more Most of the studies aiming to investigate the human tactile sense are done on the glabrous skin. Still, there is a need for a quantitative method for evaluating nervous function of the hairy skin. Tactile direction discrimination, the ability to determine the direction of movement across the skin provides a clinical method to quantify tactile function of the hairy skin in humans. The method is easy-to-use, rapid, and inexpensive but has not been compared to vibration detection which is considered as the standard method for psychophysical examination of peripheral neuropathy. The peripheral neural mechanisms for tactile direction discrimination have been extensively studied, as well as the ascending pathways in the spinal cord. Nevertheless, the supraspinal mechanisms are imperfectly known. In this study we have compared the clinical test for tactile direction discrimination with vibration detection in a group of patients with diabetic neuropathy. We have also thoroughly studied the cortical processing of tactile direction discrimination. The results are presented in four separate papers. The results showed that the clinical test for tactile direction discrimination had similar sensitivity as vibration detection in detecting patients with diabetic neuropathy. The cortical network for tactile direction discrimination involved the primary somatosensory cortex, the opercular parietal area 1 of the secondary somatosensory cortex, and dorsolateral prefrontal cortex as well as anterior insular cortex. In conclusion, the clinical test for tactile direction discrimination provides a quantitative clinical test that is sensitive in detecting peripheral nervous lesions. The test seems well-suited for following patients with disturbances in the peripheral and central nervous systems. The neurophysiological mechanisms underlying tactile direction discrimination are well studied from the peripheral afferents in the skin, through the spinal cord and to information processing in the brain.
Sudden, unexpected stimuli can induce a transient inhibition of sympathetic vasoconstriction to s... more Sudden, unexpected stimuli can induce a transient inhibition of sympathetic vasoconstriction to skeletal muscle, indicating a link to defense reactions. This phenomenon is relatively stable within, but differs between, individuals. It correlates with blood pressure reactivity which is associated with cardiovascular risk. Inhibition of muscle sympathetic nerve activity (MSNA) is currently characterized through invasive microneurography in peripheral nerves. We recently reported that brain neural oscillatory power in the beta spectrum (beta rebound) recorded with magnetoencephalography (MEG) correlated closely with stimulus-induced MSNA inhibition. Aiming for a clinically more available surrogate variable reflecting MSNA inhibition, we investigated whether a similar approach with electroencephalography (EEG) can accurately gauge stimulus-induced beta rebound. We found that beta rebound shows similar tendencies to correlate with MSNA inhibition, but these EEG data lack the robustness o...
An individual’s blood pressure (BP) reactivity to stress is linked to increased risk of hypertens... more An individual’s blood pressure (BP) reactivity to stress is linked to increased risk of hypertension and cardiovascular disease. However, inter- and intra-individual BP variability makes understanding the coupling between stress, BP reactivity, and long-term outcomes challenging. Previous microneurographic studies of sympathetic signaling to muscle vasculature (i.e. muscle sympathetic nerve activity, MSNA) have established a neural predictor for an individual’s BP reactivity during short-lasting stress. Unfortunately, this method is invasive, technically demanding, and time-consuming and thus not optimal for widespread use. Potential central nervous system correlates have not been investigated. We used MagnetoEncephaloGraphy and Magnetic Resonance Imaging to search for neural correlates to sympathetic response profiles within the central autonomic network and sensorimotor (Rolandic) regions in 20 healthy young males. The main correlates include (a) Rolandic beta rebound and an anter...
Sensing movements across the skin surface is a complex task for the tactile sensory system, relyi... more Sensing movements across the skin surface is a complex task for the tactile sensory system, relying on sophisticated cortical processing. Functional MRI has shown that judgements of the direction of tactile stimuli moving across the skin are processed in distributed cortical areas in healthy humans. To further study which brain areas are important for tactile direction discrimination, we performed a lesion study, examining a group of patients with first-time stroke. We measured tactile direction discrimination in 44 patients, bilaterally on the dorsum of the hands and feet, within 2 weeks (acute), and again in 28 patients 3 months after stroke. The 3-month follow-up also included a structural MRI scan for lesion delineation. Fifty-nine healthy participants were examined for normative direction discrimination values. We found abnormal tactile direction discrimination in 29/44 patients in the acute phase, and in 21/28 3 months after stroke. Lesions that included the opercular parietal...
Background: The impact of renal denervation (RDN) on muscle sympathetic nerve activity (MSNA) at ... more Background: The impact of renal denervation (RDN) on muscle sympathetic nerve activity (MSNA) at rest remains controversial. Mental stress (MS) induces transient changes in sympathetic nerve activity, heart rate (HR) and blood pressure (BP). It is not known whether RDN modifies these changes. Purpose: The main objective was to assess the effect of RDN on MSNA and BP alterations during MS. Methods: In 14 patients (11 included in analysis) with resistant hypertension multi-unit MSNA, BP (Finometer ®) and HR were assessed at rest and during forced arithmetics at baseline and 6 months after RDN. Results: Systolic office BP decreased significantly 6 months after RDN (185 ± 29 vs.175 ± 33 mmHG; p = 0.04). No significant changes in MSNA at rest (68 ± 5 vs 73 ± 5 bursts/100hb; p = 0.43) were noted and no significant stress-induced change in group averaged sympathetic activity was found pre-(101 ± 24%; p = 0.9) or post-intervention (108 ± 26%; p = 0.37). Stress was associated with significant increases in mean arterial BP (p < 0.01) and HR (p < 0.01) at baseline, reactions which remained unaltered after intervention. We did not note any correlation between sympathetic nerve activity and BP changes after RDN. Conclusion: Thus, in our group of resistant hypertensives we find no support for the hypothesis that the BP-lowering effect of RDN depends on altered neurovascular responses to stress.
BackgroundC‐tactile (CT) afferents are unmyelinated low‐threshold mechanoreceptors optimized for ... more BackgroundC‐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.MethodsIn total, 44 healthy volunteers experienced heat pain and CT optimal (slow brushing) and CT sub‐optimal (fast brushing or vibration) stimuli. Three different experimental paradigms were used: Concurrent application of heat pain and tactile (slow brushing or vibration) stimulation; Slow brushing, applied for variable duration and intervals, preceding heat pain; Slow versus fast brushing preceding heat pain.ResultsSlow brushing was effective in reducing pain, whereas fast brushing or vibration was not. The reduction in pain was significant not only when the CT optimal touch was applied simultaneously with the painful stimulus but also when the two stimuli were separated in time. For subsequent stimulation, the pain reduction was more prono...
Microneurographic recordings of human muscle sympathetic nerve activity responses to sudden senso... more 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 la...
The anti-migraine drug sumatriptan often induces unpleasant somatosensory side effects, including... more 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&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;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.
We have investigated cortical processing of tactile direction discrimination (TDD) in a patient w... more 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 2 mm 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 patient's 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.
Direction discrimination of a moving tactile stimulus requires intact dorsal columns and provides... more Direction discrimination of a moving tactile stimulus requires intact dorsal columns and provides a sensitive clinical test of somatosensory dysfunction. Cortical mechanisms are poorly understood. We have applied tangential skin pulls to the right lower leg during functional magnetic resonance imaging. Healthy subjects judged the direction of the skin pulls (task experiment, n = 7) or received skin pulls passively (no task experiment, n = 8). Second somatosensory cortex (S2) was activated in the task as well as no task experiment, and there was no signiWcant diVerence in cortical activation between the two experiments. Within S2 nearly all subjects had prominent activations in the caudal and superWcial part, i.e., in the opercular parietal (OP) area 1. S1 was activated in only one of the subjects. Thus, S2 and especially OP 1 seems to be important for processing of lateral skin stretch stimulation. The Wnding suggests that a lesion of this area might cause a disturbance in tactile direction discrimination which should be relevant for clinical testing.
Most of the studies aiming to investigate the human tactile sense are done on the glabrous skin. ... more Most of the studies aiming to investigate the human tactile sense are done on the glabrous skin. Still, there is a need for a quantitative method for evaluating nervous function of the hairy skin. Tactile direction discrimination, the ability to determine the direction of movement across the skin provides a clinical method to quantify tactile function of the hairy skin in humans. The method is easy-to-use, rapid, and inexpensive but has not been compared to vibration detection which is considered as the standard method for psychophysical examination of peripheral neuropathy. The peripheral neural mechanisms for tactile direction discrimination have been extensively studied, as well as the ascending pathways in the spinal cord. Nevertheless, the supraspinal mechanisms are imperfectly known. In this study we have compared the clinical test for tactile direction discrimination with vibration detection in a group of patients with diabetic neuropathy. We have also thoroughly studied the cortical processing of tactile direction discrimination. The results are presented in four separate papers. The results showed that the clinical test for tactile direction discrimination had similar sensitivity as vibration detection in detecting patients with diabetic neuropathy. The cortical network for tactile direction discrimination involved the primary somatosensory cortex, the opercular parietal area 1 of the secondary somatosensory cortex, and dorsolateral prefrontal cortex as well as anterior insular cortex. In conclusion, the clinical test for tactile direction discrimination provides a quantitative clinical test that is sensitive in detecting peripheral nervous lesions. The test seems well-suited for following patients with disturbances in the peripheral and central nervous systems. The neurophysiological mechanisms underlying tactile direction discrimination are well studied from the peripheral afferents in the skin, through the spinal cord and to information processing in the brain.
Background: Neuronal networks with a so-called 'smallworld' topography (characterized by strong l... more Background: Neuronal networks with a so-called 'smallworld' 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-, during-and 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.
Unpleasant sensory symptoms are commonly reported in association with the use of 5-HT1B/1D-agonis... more 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. Measurement...
Tactile direction discrimination and vibration detection in diabetic neuropathy Patients Patients... more Tactile direction discrimination and vibration detection in diabetic neuropathy Patients Patients with type 1 diabetes mellitus were recruited from an outpatient clinic. In a first evaluation, the participants were carefully
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Papers by Linda Lundblad