254 GENERALIZED SOMATOSENSORY CHANGES IN PATIENTS WITH TEMPOROMANDIBULAR DISORDER
Pseudoradicular and radicular low-back pain – A disease continuum rather than different entities? Rebuttal: Reply to the letter “Cheese and Chalk? Missing the real anatomy” by Breck McKay
Insula and sensory insular cortex and somatosensory control in patients with insular stroke
Background In functional imaging studies, the insular cortex (IC) has been identified as an essential part of the processing of a whole spectrum of multimodal sensory input. However, there are no lesion studies including a sufficient number of patients, which would reinforce the functional imaging data obtained from healthy subjects. Such lesion studies should examine how damage to the IC affects sensory perception. We chose acute stroke patients with lesions affecting the IC in order to fill this gap. Methods A comprehensive sensory profiling by applying a quantitative sensory testing protocol was performed and a voxel-lesion behaviour mapping analysis in 24 patients with acute unilateral …
Corrigendum to “Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): Standardized protocol and reference values” [Pain 123 (2006) 231–243]
a Institute of Physiology and Pathophysiology, Johannes Gutenberg-University, Mainz, Germany b Department of Neurology, Johannes Gutenberg-University, Mainz, Germany c Division of Neurological Pain Research and Therapy, Department of Neurology, University of Kiel, Germany d Department of Pain Management, BG Kliniken Bergmannsheil, Ruhr University Bochum, Germany e Department of Neurology, Technische Universitat Munchen, Germany f Department of Anaesthesiology, Ludwig-Maximilians-Universitat Munchen, Germany g Institute of Medical Psychology and Behavioural Neurobiology, University of Tubingen, Germany h Department of Neurology, University of Freiburg, Germany i Department of Clinical and Co…
Schmerzbehandlung in der Palliativmedizin
Schmerzen in einer palliativen Situation entstehen oft in Zusammenhang mit einer Tumorerkrankung oder der Behandlung. Der Schmerz kann als rein nozizeptiv oder neuropathisch charakterisiert werden; haufig liegt eine Kombination vor. Der diagnostische „Work-up“ soll Screening-Fragebogen, Schmerzzeichnungen, eine sorgfaltige klinische Untersuchung zur Erfassung klinischer Zeichen einer veranderten Schmerzempfindlichkeit sowie bildgebende Verfahren (CT, MRT) und ggf. klassische Elektrophysiologie (Neurografie, SEP) umfassen. Die Tumorschmerztherapie soll nach dem WHO-Stufenschema erfolgen. Aber auch neurologische Erkrankungen wie eine amyotrophe Lateralsklerose (ALS) oder eine fortgeschritten…
Basal opioid receptor binding is associated with differences in sensory perception in healthy human subjects: a [18F]diprenorphine PET study.
The endogenous opioid system is involved in many body functions including pain processing and analgesia. To determine the role of basal opioid receptor availability in the brain in pain perception, twenty-three healthy subjects underwent positron emission tomography (PET) utilizing the subtype-nonselective opioid antagonist [(18)F]diprenorphine, quantitative sensory testing (QST) and the cold pressor test. Binding potentials (BPs) were calculated using a non-invasive reference tissue model and statistical parametric mapping was applied for t-statistical analysis on a voxelwise basis. We found that cold pain-sensitive subjects present a significantly lower BP in regions including the bilater…
The pattern and time course of somatosensory changes in the human UVB sunburn model reveal the presence of peripheral and central sensitization.
The ultraviolet B (UVB) sunburn model was characterized with a comprehensive battery of quantitative sensory testing (QST). Primary hyperalgesia in UVB-irradiated skin and secondary hyperalgesia in adjacent nonirradiated skin were studied in 22 healthy subjects 24h after irradiation with UVB at 3-fold minimal erythema dose of a skin area 5 cm in diameter at the thigh and compared to mirror-image contralateral control areas. The time course of hyperalgesia over 96 h was studied in a subgroup of 12 subjects. Within the sunburn area, cold hyperesthesia (P=.01), profound generalized hyperalgesia to heat (P.001), cold (P.05), pinprick and pressure (P.001), and mild dynamic mechanical allodynia (…
Psychophysics, flare, and neurosecretory function in human pain models: capsaicin versus electrically evoked pain.
Intradermal capsaicin injection (CAP) and electrical current stimulation (ES) are analyzed in respect to patterns and test-retest reliability of pain as well as sensory and neurosecretory changes. In 10 healthy subjects, 2 CAP (50 g) and 2 ES (5 to 30 mA) were applied to the volar forearm. The time period between 2 identical stimulations was about 4 months. Pain ratings, areas of mechanical hyperalgesia, and allodynia were assessed. The intensity of sensory changes was quantified by using quantitative sensory testing. Neurogenic flare was assessed by using laser Doppler imaging. Calcito- nin gene-related peptide (CGRP) release was quantified by dermal microdialysis in combination with an en…
Pain elicited by blunt pressure: neurobiological basis and clinical relevance.
255 QUANTITATIVE SENSORY TESTING: ASSESSMENT OF THE NEUROPATHIC COMPONENT IN CANCER PAIN
Somatosensory profiles in subgroups of patients with myogenic temporomandibular disorders and Fibromyalgia Syndrome.
Some patients with myofascial pain from temporomandibular disorders (TMD) report pain in extra-trigeminal body regions. Our aim was to distinguish TMD as regional musculoskeletal pain syndrome (n=23) from a widespread pain syndrome (FMS; n=18) based on patients' tender point scores, pain drawings and quantitative sensory testing (QST) profiles. Referenced to 18 age- and gender-matched healthy subjects significant group differences for cold, pressure and pinprick pain thresholds, suprathreshold pinprick sensitivity and mechanical detection thresholds were found. Pain sensitivity in TMD patients ranged between those of FMS patients and healthy controls. The group of TMD patients was inhomogen…
High opiate receptor binding potential in the human lateral pain system
To determine how opiate receptor distribution is co-localized with the distribution of nociceptive areas in the human brain, eleven male healthy volunteers underwent one PET scan with the subtype-nonselective opioidergic radioligand [(18)F]fluoroethyl-diprenorphine under resting conditions. The binding potential (BP), a parameter for the regional cerebral opioid receptor availability, was computed using the occipital cortex as reference region. The following regions of interest (ROIs) were defined on individual MR images: thalamus, sensory motor strip (SI/MI area), frontal operculum, parietal operculum, anterior insular cortex, posterior insular cortex, anterior cingulate cortex (ACC; peri-…
Quantitative sensory testing compared to conventional neurological diagnostics in patients with vibration induced vasospastic syndrome
454 PAIN AND TACTILE SENSITIVITY AND PAIN‐RELATED ENDURANCE: NEW PREDICTORS FOR PAIN AND DISABILITY?
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 seco…
Erratum to “Human surrogate models of neuropathic pain” [Pain 115 (2005) 227–233]☆
Brain Edema and Intracerebral Necrosis Caused by Transcranial Low-Frequency 20-kHz Ultrasound
Background and Purpose— Ultrasound-accelerated thrombolysis is a promising approach toward acute stroke treatment. In previous in vitro studies, we demonstrated enhanced thrombus destruction induced by 20-kHz ultrasound. However, little is known about biological interactions of low-frequency ultrasound with brain tissue. The aim of this in vivo MRI study was to assess safety aspects of transcranial low-frequency ultrasound in rats. Methods— The cranium of 33 male Wistar rats was sonificated for 20 minutes (20-kHz continuous wave). Power output was varied between 0 and 2.6 W/cm 2 . Tympanal and rectal temperature was monitored. Diffusion-weighted imaging and T2-weighted imaging was performe…
Hand-arm vibration syndrome: clinical characteristics, conventional electrophysiology and quantitative sensory testing.
Abstract Objective Workers exposed to vibrating tools may develop hand-arm vibration syndrome (HAVS). We assessed the somatosensory phenotype using quantitative sensory testing (QST) in comparison to electrophysiology to characterize (1) the most sensitive QST parameter for detecting sensory loss, (2) the correlation of QST and electrophysiology, and (3) the frequency of a carpal tunnel syndrome (CTS) in HAVS. Methods QST, cold provocation tests, fine motor skills, and median nerve neurography were used. QST included thermal and mechanical detection and pain thresholds. Results Thirty-two patients were examined (54 ± 11 years, 91% men) at the more affected hand compared to 16 matched contro…
65 QUANTITATIVE SENSORY TESTING: ASSESSMENT OF THE NEUROPATHIC COMPONENT IN LOW BACK PAIN
Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): Standardized protocol and reference values
The nationwide multicenter trials of the German Research Network on Neuropathic Pain (DFNS) aim to characterize the somatosensory phenotype of patients with neuropathic pain. For this purpose, we have implemented a standardized quantitative sensory testing (QST) protocol giving a complete profile for one region within 30 min. To judge plus or minus signs in patients we have now established age- and gender-matched absolute and relative QST reference values from 180 healthy subjects, assessed bilaterally over face, hand and foot. We determined thermal detection and pain thresholds including a test for paradoxical heat sensations, mechanical detection thresholds to von Frey filaments and a 64 …
Human surrogate models of neuropathic pain.
Neuropathic pain is defined as pain initiated or caused by a primary lesion or dysfunction in the nervous system (Merskey and Bogduk, 1994). Current efforts to refine this definition focus on the terms ‘dysfunction’ and ‘nervous system’ with the intention to clarify that there has to be an identifiable lesion or disease process affecting the somatosensory system. Experimental models of neuropathic pain according to either one of these definitions are expected to imitate mechanisms of nerve damage within the peripheral or central parts of the somatosensory system and the ensuing processes of degeneration and regeneration. Whereas this approach to model the etiology and pathophysiology of the…
Transcranial direct current stimulation of the motor cortex induces distinct changes in thermal and mechanical sensory percepts
Abstract Objective The aim of this single-blinded, complete crossover study was to evaluate the effects of tDCS on thermal and mechanical perception, as assessed by quantitative sensory testing (QST). Methods QST was performed upon the radial part of both hands of eight healthy subjects (3 female, 5 male, 25–41 years of age). These subjects were examined before and after cathodal, anodal or sham tDCS, applied in a random order. TDCS was administered for 15 min at a 1 mA current intensity, with the active electrode placed over the left primary motor cortex and the reference electrode above the right orbit. Results After cathodal tDCS, cold detection thresholds (CDT), mechanical detection thr…
Reply: Sensory profile in primary restless legs syndrome and restless legs syndrome associated with small fibre neuropathy
Sir, We wish to thank the editor for giving us the opportunity to respond to this letter. We appreciated reading that Drs Gemignani and Vitetta think our study (Bachmann et al. , 2010) provides support for the differential diagnosis of primary and secondary restless legs syndrome (RLS) associated with small fibre neuropathy, when comparing the sensory profiles of these groups of patients for the first time. Dr Gemignani recently wrote ‘A general consensus on the proposed criteria for the diagnosis of small fibre neuropathy has not been established’ (Gemignani, 2010 b ). This already applies for small fibre neuropathy without complicating RLS; however, for the constellation of RLS with small…
Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): Somatosensory abnormalities in 1236 patients with different neuropathic pain syndromes
Neuropathic pain is accompanied by both positive and negative sensory signs. To explore the spectrum of sensory abnormalities, 1236 patients with a clinical diagnosis of neuropathic pain were assessed by quantitative sensory testing (QST) following the protocol of DFNS (German Research Network on Neuropathic Pain), using both thermal and mechanical nociceptive as well as non-nociceptive stimuli. Data distributions showed a systematic shift to hyperalgesia for nociceptive, and to hypoesthesia for non-nociceptive parameters. Across all parameters, 92% of the patients presented at least one abnormality. Thermosensory or mechanical hypoesthesia (up to 41%) was more frequent than hypoalgesia (up…
Treatment of painful radiculopathies with capsaicin 8% cutaneous patch.
The treatment of neuropathic pain due to low-back (lumbosacral) radiculopathies, a common source of neuropathic pain, is challenging and often requires a multimodal therapeutic approach. The capsaicin 8% patch is the first topical analgesic licensed for peripheral neuropathic pain. To evaluate this treatment, a subset of patients with painful radiculopathy (lumbar and cervical, including ventral and dorsal rami) enrolled into the multicenter, non-interventional QUEPP study (QutenzaOf the 1044 study participants, 50 were diagnosed with painful radiculopathy as only peripheral neuropathic pain syndrome and were eligible for evaluation. Patients received a single treatment (visit 1) with follo…
200 TEST/RETEST- AND INTEROBSERVER-RELIABILITIY IN QUANTITATIVE SENSORY TESTING ACCORDING TO THE PROTOCOL OF THE GERMAN NETWORK ON NEUROPATHIC PAIN (DFNS)
Habituation and short-term repeatability of thermal testing in healthy human subjects and patients with chronic non-neuropathic pain
We investigated habituation effects during thermal quantitative sensory testing (tQST) using 8 repetitive measurements for thermal detection and pain thresholds. The same measurements were repeated two days later. 39 healthy subjects and 36 patients with chronic non-neuropathic pain syndromes (migraine, tension-type headache, non-radicular back pain) were enrolled. The pain intensity was assessed using an 11-point (0-10) numerical rating scale. Measurements correlated significantly over the two days in both groups (r=0.41...0.62). Warm detection (WDT) and heat pain threshold (HPT) revealed no significant differences over these days. Cold detection (CDT) and pain thresholds (CPT) showed sign…
Differential expression patterns of cytokines in complex regional pain syndrome.
Complex regional pain syndromes (CRPS) are characterized by persistent and severe pain after trauma or surgery. Neuro-immune alterations are assumed to play a pathophysiological role. Here we set out to investigate whether patients with CRPS have altered systemic pro- and anti-inflammatory cytokine profiles compared to controls on mRNA and protein level. We studied blood cytokine mRNA and protein levels of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF), interleukin-2 (IL-2) and IL-8 and the anti-inflammatory cytokines IL-4, IL-10, and transforming growth factor-beta1 (TGF beta 1) in 40 prospectively recruited patients with CRPS I, two patients with CRPS II, and 34 controls…
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, p0.001): mean thresholds and 95% confidence intervals were 615 kPa (26…
Numbness in clinical and experimental pain – A cross-sectional study exploring the mechanisms of reduced tactile function
Pain patients often report distinct numbness of the painful skin although no structural peripheral or central nerve lesion is obvious. In this cross-sectional study we assessed the reduction of tactile function and studied underlying mechanisms in patients with chronic pain and in healthy participants exposed to phasic and tonic experimental nociceptive stimulation. Mechanical detection (MDT) and pain thresholds (MPT) were assessed in the painful area and the non-painful contralateral side in 10 patients with unilateral musculoskeletal pain. Additionally, 10 healthy participants were exposed to nociceptive stimulation applied to the volar forearms (capsaicin; electrical stimulation, twice e…
63 Workshop Summary: ASSESSMENT AND TREATMENT OF NEUROPATHIC BACK PAIN
Transient Receptor Potential Channel Polymorphisms Are Associated with the Somatosensory Function in Neuropathic Pain Patients
Transient receptor potential channels are important mediators of thermal and mechanical stimuli and play an important role in neuropathic pain. The contribution of hereditary variants in the genes of transient receptor potential channels to neuropathic pain is unknown. We investigated the frequency of transient receptor potential ankyrin 1, transient receptor potential melastin 8 and transient receptor potential vanilloid 1 single nucleotide polymorphisms and their impact on somatosensory abnormalities in neuropathic pain patients. Within the German Research Network on Neuropathic Pain (Deutscher Forscbungsverbund Neuropathischer Schmerz) 371 neuropathic pain patients were phenotypically ch…
Different short-term modulation of cortical motor output to distal and proximal upper-limb muscles during painful sensory nerve stimulation
The pattern of upper-limb muscle activation following painful stimulation has not been clarified in detail. We investigated the short-term inhibitory and excitatory effects of painful electrical digital stimulation on the motoneuron pools of distal and proximal upper-limb muscles. Transcranial magnetic stimulation (TMS) was used as test stimulus, and painful digital nerve stimulation as conditioning stimulus for motor evoked potential (MEP) recordings over the abductor digiti minimi (ADM), abductor pollicis brevis (APB), biceps brachii (BB), and deltoid muscles. Inhibition of the conditioned MEP response was most prominent in the distal muscles, whereas BB and deltoid muscles were only weak…
Sensory neuropathy and signs of central sensitization in patients with peripheral arterial disease.
Patients with peripheral arterial disease (PAD) may develop a broad range of peripheral nerve dysfunctions including pain and sensory deficiencies due to chronic ischemia mostly involving the lower limbs. To investigate the degree of sensory abnormalities in such patients quantitative sensory testing (QST) might be a useful tool. Forty-five patients and 20 controls were enrolled in the present study and underwent QST according to the protocol of the German Research Network on Neuropathic Pain. PAD was graded according to the Rutherford classification. PAD patients were divided into two groups: 16 patients with critical limb ischemia (severe PAD) and 29 patients with intermittent claudicatio…
Pseudoradicular and radicular low-back pain--a disease continuum rather than different entities? Answers from quantitative sensory testing.
To assess whether pseudoradicular low-back pain may be associated with subclinical sensory deficits in the distal extremity, we applied the quantitative sensory testing protocol of the German Research Network on Neuropathic Pain (DFNS) in 15 patients with pseudoradicular pain distribution. Sixteen age- and gender-matched healthy control subjects as well as 12 patients with radicular pain syndromes (L4-S1) were studied with the same protocol. Radicular pain was diagnosed using clinical criteria (pain radiation beyond the knee, motor-, sensory-, or reflex deficits, positive Lasegue's test). Z-score QST profiles revealed a selective loss of vibration detection, detection of v. Frey hair contac…
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 fo…
Pseudoradicular and radicular low-back pain – A disease continuum rather than different entities? Rebuttal: Reply to the letter by M. Schiltenwolf and M. Akbar
Left-hemispheric dominance for articulation: a prospective study on acute ischaemic dysarthria at different localizations.
Dysarthria is a frequent symptom in cerebral ischaemia. However, speech characteristics of these patients have not previously been investigated in relation to lesion site in a prospective study. We investigated the auditory perceptual features in 62 consecutive patients with dysarthria due to a single, non-space-occupying cerebral infarction confirmed by MRI. Standardized speech samples of all patients were stored within 72 h after stroke onset using a digital tape recorder. Speech samples were assessed independently by two experienced speech therapists, who were unaware of the clinical and neuroradiological findings, using an interval scale ranging from 0 to 6. Separately assessed were fea…
Effects of transcranial direct current stimulation of the primary sensory cortex on somatosensory perception.
Background: Transcranial direct current stimulation (tDCS) is able to modify cortical excitability and activity in humans. Objective: The aim of the present study was to analyze the effects of tDCS of the primary sensory cortex (SI) on thermal and mechanical perception, assessed by quantitative sensory testing (QST). Methods: The comprehensive QST protocol encompassing thermal and mechanical detection and pain thresholds as devised by the German Research Network on Neuropathic Pain (DFNS) was applied to skin areas innervated by the radial and median nerve of 12 healthy subjects, who were examined before and after each tDCS stimulation type. Anodal, cathodal, and sham tDCS was applied at a 1…
Thermal hypoaesthesia differentiates secondary restless legs syndrome associated with small fibre neuropathy from primary restless legs syndrome.
This study aimed to assess thermal and mechanical perception and pain thresholds in primary idiopathic restless legs syndrome and secondary restless legs syndrome associated with small fibre neuropathy. Twenty-one patients (age: 53.4 + or - 8.4, n = 3, male) with primary restless legs syndrome and 13 patients (age: 63.0 + or - 8.2, n = 1, male) with secondary restless legs syndrome associated with small fibre neuropathy were compared with 20 healthy subjects (age: 58.0 + or - 7.0; n = 2, male). Differential diagnosis of secondary restless legs syndrome associated with small fibre neuropathy was based on clinical symptoms and confirmed with skin biopsies in all patients. A comprehensive quan…
Thermal Thresholds Predict Painfulness of Diabetic Neuropathies
OBJECTIVE—Pathophysiology explaining pain in diabetic neuropathy (DN) is still unknown. RESEARCH DESIGN AND METHODS—Thirty patients with peripheral DN (17 men and 13 women; mean age 52.4 ± 2.5 years) were investigated. Fifteen patients had neuropathic pain, and 15 patients were free of pain. Patients were followed over 2 years and examined at the beginning and thereafter every 6 months. Clinical severity and painfulness of the DN were assessed by the neuropathy impairment score and visual analog scales (VASs). Cold and warm perception thresholds as well as heat pain thresholds were obtained for evaluation of Aδ- and C-fibers. Nerve conduction velocities (NCVs) and vibratory thresholds were …
87 Topical Seminar Summary: QUANTITATIVE SENSORY TESTING (QST) IN PAIN MEDICINE: WHAT IS ITS VALUE IN CLINICAL PRACTICE?
A family-based investigation of cold pain tolerance
In the present study the question was addressed whether sensitivity to experimental pain stimuli differs between families, which are previously characterized by the degree of cold tolerance (very insensitive or very sensitive) of one family member. A total of 232 healthy medical students were screened for cold pain tolerance employing a cold pressor test. Subsequently 50 of them were investigated in detail under laboratory conditions. The water temperature was 1 degrees C, the maximum time in water 3 min, cold pain was rated on a 101 step numerical rating scale every 10s. Two of the most cold pain sensitive (shortest time in ice water) and insensitive (lowest ratings) students were selected…