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R-D Treede

Publications and source records attributed to R-D Treede.

12 recordsLinked to original sources
PubMed2006

Phosphorylation of extracellular signal-related protein kinase is required for rapid facilitation of heat-induced currents in rat dorsal root ganglion neurons.

A subgroup of dorsal root ganglion (DRG) neurons responds to noxious heat with an influx of cations carried by specific ion channels such as the transient receptor potential channel of the vanilloid receptor type, subtype 1 (TRPV1). Application of capsaicin induces a reversible facilitation of these currents. This facilitation could be an interaction of two agonists at their common receptor or be caused by an influx of calcium ions into the cell. Calcium influx into the cell can activate protein kinases such as the extracellular signal-related protein kinase (ERK) pathway. This study explored the kinetics, calcium-dependency and intracellular signals following application of capsaicin and leading to facilitation of heat-induced currents (Iheat) in rat DRG neurons. Application of 0.5 microM capsaicin caused a 2.65-fold increase of Iheat within 2 s, which was significantly correlated to a small capsaicin-induced current. Intracellular application of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), a fast calcium chelator, did not change capsaicin-induced currents or Iheat itself, but inhibited facilitation of Iheat by capsaicin. ERK is activated by calcium influx and membrane depolarization via the mitogen-activated protein kinase/extracellular signal-related protein kinase kinase (MEK). Application of the MEK inhibitor U0126 also inhibited facilitation of Iheat by capsaicin. We conclude that the MEK/ERK cascade is an intracellular signaling pathway playing a vital role in the regulation of nociceptive neurons' sensitivity. The very fast kinetics (less than two seconds) are only explainable with a membrane-attached or at least membrane-near localization of these kinases.

Analysis of Variance↗
PubMed2006

Co-expression of the voltage-gated potassium channel Kv1.4 with transient receptor potential channels (TRPV1 and TRPV2) and the cannabinoid receptor CB1 in rat dorsal root ganglion neurons.

Potassium channels contribute to basic neuronal excitability and modulation. Here, we examined expression patterns of the voltage-gated potassium channel Kv1.4, the nociceptive transduction channels TRPV1 and TRPV2 as well as the putative anti-nociceptive cannabinoid receptor CB1 by immunofluorescence double-labelings in sections of rat dorsal root ganglia (DRGs). Kv1.4, TRPV1 and CB1 were each detected in about one third of neurons (35.7+/-0.5%, 29.4+/-1.1% and 36.4+/-0.5%, respectively, mean diameter 19.1+/-0.3 microm). TRPV2 was present in 4.4+/-0.4% of all neurons that were significantly larger in diameter (27.4+/-0.7 microm; P < 0.001). Antibody double-labeling revealed that the majority of Kv1.4-positive neurons co-expressed TRPV1 (73.9+/-1.5%) whereas none expressed TRPV2. The largest overlap was found with CB1 (93.1+/-0.1%). CB1 expression resembled that seen for Kv1.4 since the majority of neurons expressing CB1-protein also expressed TRPV1 (69.4+/-6.5%) but not TRPV2 (0.6+/-0.3%). When CB1-mRNA was detected using in situ hybridizations an additional subset of larger neurons was labeled including 82.4+/-17.7% of the TRPV2 expressing neurons. However, co-localization of Kv1.4 with CB1-mRNA (92%, mean diameter: 18.5 microm) was essentially the same as with CB1-protein. The almost complete overlap of CB1 and Kv1.4 in nociceptive DRG neurons suggests a functional synergistic action between Kv1.4 and CB1. The potassium channel may have two important roles in nociception. As the molecular basis of A-type current it could be involved in the control of repetitive discharges at peripheral terminals and as a downstream signal transduction site of CB1 in the control of presynaptic transmitter release at central terminals.

Animals↗
PubMed2006

[Pain processing in patients with borderline personality disorder, fibromyalgia, and post-traumatic stress disorder].

The authors review relevant experimental studies on pain perception and processing in psychiatric disorders with traumatic stress as an etiological factor. In borderline personality disorder, post-traumatic stress disorder, and fibromyalgia neurophysiological and neuropsychological patterns of pain processing appear to be different. Experimental studies in borderline patients show a desensitization of pain thresholds whereas patients with fibromyalgia show an opposite pattern, which could be explained by a central augmentation of pain processing. Furthermore, the authors outline methods to assess pain perception (peripheral and central) and describe the neurobiological mechanisms of pain processing, particularly the distinction between the sensory-discriminative lateral system and the affective-motivational medial system. Finally, suggestions for further research and implications for therapy are proposed.

Central Nervous System↗
PubMed2006

Quantitative sensory testing: a comprehensive protocol for clinical trials.

We have compiled a comprehensive QST protocol as part of the German Research Network on Neuropathic Pain (DFNS) using well established tests for nearly all aspects of somatosensation. This protocol encompasses thermal as well as mechanical testing procedures. Our rationale was to test for patterns of sensory loss (small and large nerve fiber functions) or gain (hyperalgesia, allodynia, hyperpathia), and to assess both cutaneous and deep pain sensitivity. The practicality of the QST protocol was tested in 18 healthy subjects, 21-58 years, half of them female. All subjects were tested bilaterally over face, hand and foot. We determined thermal detection and pain thresholds including a test for the presence of paradoxical heat sensations, mechanical detection thresholds to von Frey filaments and a 64-Hz tuning fork, mechanical pain thresholds to pinprick stimuli and blunt pressure, stimulus-response-functions for pinprick and dynamic mechanical allodynia (pain to light touch), and pain summation (wind-up ratio) using repetitive pinprick stimulation. The full protocol took 27+/-2.3 min per test area. The majority of QST parameters were normally distributed only after logarithmic transformation (secondary normalization) except for the frequency of paradoxical heat sensations, cold and heat pain thresholds, and for vibration detection thresholds. Thresholds were usually lowest over face, followed by hand, and then foot. Only thermal pain thresholds, wind-up ratio and vibration detection thresholds were not significantly dependent on the body region. There was no significant right-to-left difference for any of the QST parameters; left-to-right correlation coefficients ranged between 0.78 and 0.97, thus explaining between 61% and 94% of the variance. This study has shown that a complete somatosensory profile of one affected area and one unaffected control area, which will be necessary to characterize patients with a variety of diseases, can be obtained within 1 h. Case examples of selected patients illustrate the value of z-transformed QST data for an easy survey of individual symptom profiles.

Adult↗
PubMed2006

Plasticity of pain-related neuronal activity in the human thalamus.

Strokes and other forms of injury to the central nervous system cause changes in function because of the injuries themselves and indirectly because injuries cause expression of neural plasticity. Studies in humans undergoing neurosurgical procedures for implantation of electrodes for deep brain stimulation and for making lesions in the brain have contributed understanding of both normal and abnormal functions of the somatic sensory system. This chapter will specifically discuss the reorganization of the ventral caudal (Vc) sensory nucleus of the thalamus that occurs in connection with pain conditions after strokes and spinal cord injuries. It is shown that pain is associated with expression of neural plasticity that alters maps of noxious and innocuous stimulation in the thalamus and affect processing of sensory information. Results from studies of neural activity in the thalamus in humans will be compared with results from animal studies.

Brain Injuries↗
PubMed2005

The unpleasantness of tonic pain is encoded by the insular cortex.

OBJECTIVE: Muscle pain differs from skin pain with respect to quality, accuracy of localization, and unpleasantness. This study was conducted to identify the brain regions associated with the affective-motivational component of tonic skin and muscle pain. METHODS: Forty healthy volunteers were investigated in three groups with different F-18 fluorodeoxyglucose PET activation scans. A verbal rating scale (VRS) was used to quantify pain intensity and unpleasantness. One group was investigated during painful infusion of an acidified phosphate buffer (pH 5.2) into either muscle or skin for 30 minutes. Muscle and skin infusions were adjusted to achieve pain intensity rating of VRS = 40. The second group received sham stimulation of muscle and skin by infusion of non-acidified phosphate buffer (pH 7.3 to 7.4, pain intensity = 0). The third group underwent only one PET scan without sensory stimulation. RESULTS: Unpleasantness ratings were higher (VRS 38.3 vs 25.5) during IM compared to intracutaneous stimulation, despite the same pain intensity (VRS = 40). Sham stimulation revealed no pain or unpleasantness. Regional cerebral glucose metabolism during sham stimulation showed similar findings for intracutaneous and IM infusions with significant activations of the bilateral anterior cingulate, bilateral frontal (premotor) cortex, and the ipsilateral parietal operculum. The comparison of pain vs sham stimulation revealed activations of the bilateral insula for IM but not intracutaneous stimulation. The unpleasantness perception in skin and muscle stimulation was positively correlated to the bilateral insular metabolism. CONCLUSION: The data suggest that the insula represents one main structure where the unpleasantness of tonic pain perception is encoded.

Acids↗
PubMed2005

Deep pain thresholds in the distal limbs of healthy human subjects.

Pressure pain thresholds (PPTs) in distal limbs have been under-investigated despite their potential clinical importance. Therefore, we compared PPTs over nail bed, bony prominences, and muscle in distal parts of upper and lower limbs. We investigated 12 healthy subjects using three handheld devices: a spring-loaded, analogue pressure threshold meter (PTM) with two operating ranges, and an electronic Algometer. PPTs were determined with three series of ascending stimulus intensities with a ramp of about 50 kPa/s. PPTs were normally distributed in logarithmic space. PPTs over different tissues varied significantly (ANOVA, p<0.001): mean thresholds and 95% confidence intervals were 615 kPa (266-1424 kPa) over the nail bed, 581 kPa (271-1245 kPa) over bony prominences, and 520 kPa (246-1100 kPa) over muscles. PPTs on the foot were higher than on the hand (ANOVA, p<0.01), except over muscles. PPTs were significantly lower with the Algometer than with PTMs (ANOVA, p<0.01); again these differences were least when testing over muscle. There was no significant right-left difference (ANOVA, p=0.33). In spite of considerable variability across subjects, reproducibility within subjects was high (correlation coefficients>0.90). For within-subject comparisons, threshold elevations beyond 33-43% would be abnormal (95% confidence intervals), whereas only deviations from the group mean by at least a factor of two would be abnormal with respect to absolute normative values. PPTs over distal muscles were comparable to published values on proximal limb and trunk muscles. These findings suggest that pressure pain testing over distal muscles may be a sensitive test for deep pain sensitivity and that the simple and less expensive devices are sufficient for testing this tissue type. Intra-individual site-to-site comparisons will be more sensitive than absolute normative values.

Adult↗
PubMed2004

Static mechanical hyperalgesia without dynamic tactile allodynia in patients with restless legs syndrome.

Pain sensitivity was assessed in 11 patients (age 60 +/- 10 years) with 'primary' restless leg syndrome (RLS) (disease duration 18 +/- 15 years) and 11 age- and gender-matched healthy control subjects. Stimulus-response functions for pricking pain were obtained with seven calibrated punctate mechanical stimulators activating Adelta-high threshold mechano-nociceptors. Stimuli at the foot were significantly more painful than at the hand in both patients and healthy control subjects both in the morning and evening. Generally, pin-prick pain ratings in RLS patients were significantly elevated, by a factor of 5.3 in the upper limb and by a factor of 6.4 in the lower limb indicating a significant generalized static hyperalgesia more pronounced in the lower limb. In contrast, pain to light touch (allodynia = dynamic mechanical hyperalgesia) as tested by a battery of three gentle tactile stimuli was never reported. Acute single-dose dopaminergic treatment with 100 mg levodopa + 25 mg benserazide, 90 min prior to the evening measurements, largely resolved patients' RLS symptoms, but had no effect on pin-prick pain. Static hyperalgesia to pin-prick, however, was significantly reversed (median reduction -74%) by long-term individually tailored dopaminergic treatment. Our study shows that patients with RLS exhibit a profound static mechanical hyperalgesia to pin-prick stimuli, but no dynamic mechanical hyperalgesia (allodynia). This type of hyperalgesia is probably mediated by central sensitization to Adelta-fibre high-threshold mechanoreceptor input, a hallmark sign of the hyperalgesia type of neuropathic pain. The reduction of hyperalgesia in RLS patients by long-term dopaminergic treatment suggests that the pathophysiology of RLS includes disturbed supraspinal pain modulation involving the basal ganglia and/or descending dopaminergic pathways.

Adult↗
PubMed2004

Differential effects on the laser evoked potential of selectively attending to pain localisation versus pain unpleasantness.

OBJECTIVE: To determine the effects on the laser evoked potential (LEP) of selectively attending to affective (unpleasantness) versus sensory-discriminative (localisation) components of pain. METHODS: LEPs, elicited by painful CO2 laser stimulation of two areas of the right forearm, were recorded from 62 electrodes in 21 healthy volunteers, during three tasks that were matched for generalised attention: Localisation (report stimulus location), Unpleasantness (report stimulus unpleasantness), Control (report pain detection). LEP components are named by polarity, latency, and electrode. RESULTS: N300-T7 peak amplitude was significantly greater during Localisation than Unpleasantness. The difference in N300-T7 amplitude between Localisation and Control approached significance, suggesting an increased amplitude in Localisation compared with Control, rather than a reduced amplitude in Unpleasantness. Peak amplitude, latency, and topography of N300-FCz, P450, P600-800 (early P3) and P800-1000 (late P3) did not differ significantly between tasks. CONCLUSIONS: These results suggest that the N300-T7 LEP peak reflects the activity of cerebral generators involved in the localisation of pain. The topography of N300-T7 is consistent with a source in contralateral secondary somatosensory cortex/insula and maybe primary somatosensory cortex. SIGNIFICANCE: This study confirms a role of the lateral pain system in the localisation of pain, and distinguishes it from stimulus novelty or attention.

Adult↗
PubMed2004

Amplitudes of laser evoked potential recorded from primary somatosensory, parasylvian and medial frontal cortex are graded with stimulus intensity.

Intensity encoding of painful stimuli in many brain regions has been suggested by imaging studies which cannot measure electrical activity of the brain directly. We have now examined the effect of laser stimulus intensity (three energy levels) on laser evoked potentials (LEPs) recorded directly from the human primary somatosensory (SI), parasylvian, and medial frontal cortical surfaces through subdural electrodes implanted for surgical treatment of medically intractable epilepsy. LEP N2* (early exogenous/stimulus-related potential) and LEP P2** (later endogenous potential) amplitudes were significantly related to the laser energy levels in all regions, although differences between regions were not significant. Both LEP peaks were also significantly correlated with the pain intensity evoked by the laser stimulus, excepting N2* over the parasylvian region. Peak latencies of both LEP peaks were independent of laser energy levels. N2* and P2** amplitudes of the maxima in all regions showed significant positive linear correlations with laser energy, excepting N2* over the parasylvian region. The lack of correlation of parasylvian cortical N2* with laser energy and pain intensity may be due to the unique anatomy of this region, or the small sample, rather than the lack of activation by the laser. Differences in thresholds of the energy correlation with amplitudes were not significant between regions. These results suggest that both exogenous in endogenous potentials evoked by painful stimuli, and recorded over SI, parasylvian, and medial frontal cortex of awake humans, encode the intensity of painful stimuli and correlate with the pain evoked by painful stimuli.

Adult↗
PubMed2003

Cutaneous painful laser stimuli evoke responses recorded directly from primary somatosensory cortex in awake humans.

Negative and positive laser evoked potential (LEP) peaks (N2*, P2**) were simultaneously recorded from the primary somatosensory (SI), parasylvian, and medial frontal (MF: anterior cingulate and supplementary motor area) cortical surfaces through subdural electrodes implanted for the surgical treatment of intractable epilepsy. Distribution of the LEP N2* and P2** peaks was estimated to be in cortical areas (SI, parasylvian, and MF) identified by anatomic criteria, by their response to innocuous vibratory stimulation of a finger (v-SEP), and to electrical stimulation of the median nerve (e-SEP). The maximum of the LEP N2* peak was located on the CS, medial (dorsal) to the finger motor area, as determined by cortical stimulation, and to the finger somatosensory area, as determined from the e-SEP and v-SEP. This finding suggests that the generator source of the LEP N2* peak in SI was different from that of e-SEP or v-SEP in Brodmann's areas 3b or 1. In parasylvian and MF, polarity reversal was often observed, indicating tangential current sources in these regions. In contrast to e-SEP and v-SEP, the LEP N2* latency over SI was not shorter than that over the parasylvian region. The amplitude of N2* was larger over SI than over MF and the latencies of the LEP peaks in those 2 regions were different. These findings provide evidence for a significant LEP generator in the postcentral gyrus, perhaps SI cortex, that is situated outside the tactile homunculus in SI and that receives its input arising from nociceptors simultaneously with parasylvian and MF cortex.

Adult↗