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Biomedical subjects

Hermann O Handwerker

Publications and source records attributed to Hermann O Handwerker.

18 recordsLinked to original sources
PubMed2006

Mislocalization of tactile stimulation in patients with complex regional pain syndrome.

Complex-Regional-Pain-Syndromes (CRPS) are characterized by sensory,motor and autonomic dysfunctions. Patterns of sensory symptoms suggest changes within the central nervous system (CNS). Recently, we could show substantial reorganization of somatotopic maps within the central nervous system of patients with CRPS using functional imaging techniques (Maihofner et al. Neurology, 2003). These changes were predicted by CRPS pain and mechanical hyperalgesia. In the present study we looked for potential psychophysical correlates of cortical reorganization in CRPS. Sequential pneumatic non-noxious tactile stimulation was performed at digits 1 and 5 in 24 patients with CRPS of the upper extremities. Both the unaffected and affected side were examined. Patients were interviewed for tactile induced sensations. The occurrence of mislocalizations was correlated with a detailed psychophysical examination in which sensory, motor and autonomic symptoms were assessed. Eight patients (30 %) reported tactile mislocalizations, which were felt in the affected hand. In four cases the referred sensations spread into other nerve territories (ulnar/median nerve). Presence of mechanical hyperalgesia significantly predicted the occurrence of mislocalizations. In contrast, in a healthy control group, no mislocalizations were found. Thus, our results further support the concept of pain-induced reorganization in the somatosensory system of CRPS patients.

Adult↗
PubMed2006

Functional imaging of allodynia in complex regional pain syndrome.

OBJECTIVE: To investigate cerebral activations underlying touch-evoked pain (dynamic-mechanical allodynia) in patients with neuropathic pain. METHODS: fMRI was used in 12 patients with complex regional pain syndromes (CRPSs). Allodynia was elicited by gently brushing the affected CRPS hand. Elicited pain ratings were recorded online to obtain pain-weighted predictors. Both activations and deactivations of blood oxygenation level-dependent signals were investigated. RESULTS: Nonpainful stimulation on the nonaffected hand activated contralateral primary somatosensory cortex (S1), bilateral insula, and secondary somatosensory cortices (S2). In contrast, allodynia led to widespread cerebral activations, including contralateral S1 and motor cortex (M1), parietal association cortices (PA), bilateral S2, insula, frontal cortices, and both anterior and posterior parts of the cingulate cortex (aACC and pACC). Deactivations were detected in the visual, vestibular, and temporal cortices. When rating-weighted predictors were implemented, only few activations remained (S1/PA cortex, bilateral S2/insular cortices, pACC). CONCLUSIONS: Allodynic stimulation recruits a complex cortical network. Activations include not only nociceptive but also motor and cognitive processing. Using a covariance approach (i.e., implementation of rating-weighted predictors) facilitates the detection of a neuronal matrix involved in the encoding of allodynia. The pattern of cortical deactivation during allodynia may hint at a shift of activation from tonically active sensory systems, like visual and vestibular cortices, into somatosensory-related brain areas.

Adult↗
PubMed2005

Differential coding of hyperalgesia in the human brain: a functional MRI study.

Neuropathic pain can be both ongoing or stimulus-induced. Stimulus-induced pain, also known as hyperalgesia, can be differentiated into primary and secondary hyperalgesia. The former results from sensitization of peripheral nociceptive structures, the latter involves sensitization processes within the central nervous system (CNS). Hypersensitivity towards heat stimuli, i.e. thermal hyperalgesia, is a key feature of primary hyperalgesia, whereas secondary hyperalgesia is characterized by hypersensitivity towards mechanical (e.g. pin-prick) stimulation. Using functional magnetic resonance imaging (fMRI), we investigated if brain activation patterns associated with primary and secondary hyperalgesia might differ. Thermal and pin-prick hyperalgesia were induced on the left forearm in 12 healthy subjects by topical capsaicin (2.5%, 30 min) application. Equal pain intensities of both hyperalgesia types were applied during fMRI experiments, based on previous quantitative sensory testing. Simultaneously, subjects had to rate the unpleasantness of stimulus-related pain. Pin-prick hyperalgesia (i.e. subtraction of brain activations during pin-prick stimulation before and after capsaicin exposure) led to activations of primary and secondary somatosensory cortices (S1 and S2), associative-somatosensory cortices, insula and superior and inferior frontal cortices (SFC, IFC). Brain areas activated during thermal hyperalgesia (i.e. subtraction of brain activations during thermal stimulation before and after capsaicin exposure) were S1 and S2, insula, associative-somatosensory cortices, cingulate cortex (GC), SFC, middle frontal cortex (MFC) and IFC. When compared to pin-prick hyperalgesia, thermal hyperalgesia led to an increased activation of bilateral anterior insular cortices, MFC, GC (Brodmann area 24' and 32') and contralateral SFC and IFC, despite equal pain intensities. Interestingly, stronger activations of GC, contralateral MFC and anterior insula significantly correlated to higher ratings of the stimulus-related unpleasantness. We conclude that thermal and mechanical hyperalgesia produce substantially different brain activation patterns. This is linked to different psychophysical properties.

Adult↗
PubMed2005

Mechanical hyperalgesia in complex regional pain syndrome: a role for TNF-alpha?

Plasma concentrations of soluble tumor necrosis factor alpha (TNF-alpha) receptor type I (sTNF-RI) were assessed in two complex regional pain syndrome (CRPS) patient groups (n = 30 and n = 16) and healthy controls (n = 25). Patients with CRPS and mechanical hyperalgesia had higher levels of sTNF-RI (1,661.8 +/- 146.8 pg/mL) compared with those with CRPS with identical clinical appearance but without hyperalgesia (1,155.9 +/- 56.3 pg/mL) and controls (1,239.5 +/- 42.9 pg/mL). This study suggests involvement of TNF-alpha in mechanical hyperalgesia of CRPS.

Adult↗
PubMed2005

Brain processing during mechanical hyperalgesia in complex regional pain syndrome: a functional MRI study.

Complex Regional Pain Syndromes (CRPS) are characterized by a triad of sensory, motor and autonomic dysfunctions of still unknown origin. Pain and mechanical hyperalgesia are hallmarks of CRPS. There are several lines of evidence that central nervous system (CNS) changes are crucial for the development and maintenance of mechanical hyperalgesia. However, little is known about the cortical structures associated with the processing of hyperalgesia in pain patients. This study describes the use of functional magnetic resonance imaging (fMRI) to delineate brain activations during pin-prick hyperalgesia in CRPS. Twelve patients, in whom previous quantitative sensory testing revealed the presence of hyperalgesia to punctuate mechanical stimuli (i.e. pin-prick hyperalgesia), were included in the study. Pin-prick-hyperalgesia was elicited by von-Frey filaments at the affected limb. For control, the identical stimulation was performed on the unaffected limb. fMRI was used to explore the corresponding cortical activations. Mechanical stimulation at the unaffected limb was non-painful and mainly led to an activation of the contralateral primary somatosensory cortex (S1), insula and bilateral secondary somatosensory cortices (S2). The stimulation of the affected limb was painful (mechanical hyperalgesia) and led to a significantly increased activation of the S1 cortex (contralateral), S2 (bilateral), insula (bilateral), associative-somatosensory cortices (contralateral), frontal cortices and parts of the anterior cingulate cortex. The results of our study indicate a complex cortical network activated during pin-prick hyperalgesia in CRPS. The underlying neuronal matrix comprises areas not only involved in nociceptive, but also in cognitive and motor processing.

Adult↗
PubMed2004

Cortical reorganization during recovery from complex regional pain syndrome.

OBJECTIVE: To characterize reorganization of the primary somatosensory cortex (S1) during healing process in complex regional pain syndrome (CRPS). BACKGROUND: Recently, the authors showed extensive reorganization of the S1 cortex contralateral to the CRPS affected side. Predictors for these plastic changes were CRPS pain and the extent of mechanical hyperalgesia. It is unclear how these S1 changes develop following successful therapy. METHODS: The authors used magnetic source imaging to explore changes in the cortical representation of digits (D) 1 and 5 in relation to the lower lip on the unaffected and affected CRPS side in 10 patients during a year or more of follow-up. RESULTS: Cortical reorganization reversed coincident with clinical improvement. A reduction of CRPS pain correlated with recovery from cortical reorganization. CONCLUSIONS: Changes of the somatotopic map within the S1 cortex may depend on CRPS pain and its recovery.

Adult↗
PubMed2004

Neural activation during experimental allodynia: a functional magnetic resonance imaging study.

Abstract Pain induced by gentle stroking, i.e. dynamic-mechanical allodynia, is one of the most distressing symptoms of neuropathic pain. The underlying neuronal pathways are still a matter of debate. Here, we investigated the cortical activations associated with dynamic-mechanical allodynia in an experimental human pain model by functional magnetic resonance imaging (fMRI). Large and stable areas of brush-evoked allodynia were induced in 11 healthy subjects by topical capsaicin (2.5%, 30 min) application following local heating (45 degrees C for 5 min), thus combining both physical and chemical sensitization. During the fMRI experiments, allodynia was rekindled by local heat application (40 degrees C for 5 min) immediately before the allodynia testing. Brushing the untreated forearm (control condition) led to activations of the contralateral primary somatosensory cortex (S1), contralateral parietal association cortex (PA), bilateral secondary somatosensory cortices (S2) and insula (contralateral). Brushing the allodynic skin was painful and the cortical responses were partially overlapping with those induced by the nonpainful brush stimulation. Additionally, the contralateral inferior frontal cortex (IFC) and the ipsilateral insula were activated. Direct comparison between nonpainful brushing and brush-evoked allodynia revealed significant increases in blood oxygenation level-dependent (BOLD) signals in contralateral S1, PA, IFC and bilateral S2/insula during allodynia. This study highlights the importance of a cortical network comprising S1, PA, S2/insula and IFC in the processing of dynamic-mechanical allodynia in the human brain. Furthermore, it demonstrates that the combined heat/capsaicin model can be used successfully in the exploration of brain processes underlying stimulus-evoked pain.

Adult↗
PubMed2003

Patterns of cortical reorganization in complex regional pain syndrome.

OBJECTIVE: To use magnetoencephalography to assess possible cortical reorganization in the primary somatosensory cortex (S1) of patients with complex regional pain syndrome (CRPS). BACKGROUND: Patterns of pain and sensory symptoms in CRPS may indicate plastic changes of the CNS. METHODS: Magnetic source imaging was used to explore changes in the cortical representation of digits (D) 1 and 5 in relation to the lower lip on the unaffected and affected CRPS side in 12 patients. RESULTS: The authors found a significant shrinkage of the extension of the cortical hand representation for the CRPS affected side. The center of the hand was shifted toward the cortical representation of the lip. The cortical reorganization correlated with the amount of CRPS pain (r = 0.792), as measured by the McGill questionnaire, and the extent of mechanical hyperalgesia (r = 0.860). Using multiple regression analysis, the best predictor for the plastic changes was found to be mechanical hyperalgesia. Additionally, S1 sources following tactile stimulation were significantly increased on the CRPS side compared to the unaffected limb. CONCLUSIONS: This study showed reorganization of the S1 cortex contralateral to the CRPS affected side. The reorganization appeared to be linked to complaints of neuropathic pain.

Adult↗
PubMed2003

Cortical processing of brush-evoked allodynia.

The cortical processing of allodynia (touch-evoked pain) resulting from neuralgia of the lateral cutaneous femoral nerve was investigated with a newly designed pneumatically driven brush by means of magnetoencephalography. Brushing the unaffected thigh produced subsequent activation of the contralateral primary somatosensory cortex (S1) with peak latencies of 37 and 56 ms. Brushing the affected side led to comparable activation of the contralateral S1 cortex. In addition, the magnetic fields were stronger, and the corresponding equivalent current dipoles were located more laterally, consistent with the presence of cortical reorganisation. Allodynia was also accompanied by an activation of the cingulate cortex, occurring only 92 ms. after stimulus onset, an observation suggesting an Abeta-fiber-mediated neuronal pathway involved in dynamic mechanical allodynia. This study corroborates the concept of cortical reorganisation underlying chronic pain. Furthermore, it demonstrates that a remarkable early activation of the cingulate cortex may be involved in the cortical processing of allodynia.

Cerebral Cortex↗
PubMed2003

Central origin of secondary mechanical hyperalgesia.

The contribution for the development of secondary mechanical hyperalgesia by peripheral mechanisms has not been fully elucidated. We have reevaluated the effects of local anesthetics on electrically evoked flare reaction and mechanical hyperalgesia in human skin. We applied 2% lidocaine via intradermal microdialysis fibers at a length of 10 cm for 110 min to the volar forearm to establish a narrow and stable "anesthetic strip." After 60 min of lidocaine perfusion, transdermal electrical stimulation (1 Hz, 50 mA) was applied at a distance of 1 cm from the microdialysis fibers for 30 min. The areas of allodynia and punctate hyperalgesia were marked at the end of the stimulation period. The flare reaction was assessed by laser Doppler scanner and infrared thermography. Total protein content of the dialysate collected at the stimulating electrode was measured photometrically. We found no increase in protein content during electrical stimulation. Flare area (12.4 +/- 2.3 vs. 3.5 +/- 1.2 cm2) and intensity (426 +/- 24 vs. 257 +/- 21 PU) were significantly reduced beyond the lidocaine strip. The mean temperature increase in the area beyond the lidocaine strip was significantly reduced (1.1 +/- 0.1 vs. 0.2 +/- 0.1 degrees C) and did not differ from control areas. In contrast, allodynia (7.4 +/- 0.7 and 8.6 +/- 0.9 cm) and punctate hyperalgesia (7.6 +/- 0.7 and 8.6 +/- 0.9 cm) developed symmetrically on both sides of the anesthetic strip. Allodynia subsided 4 min after the end of the electrical stimulation. We conclude that the development of allodynia and punctate hyperalgesia in human skin is centrally mediated, whereas the axon reflex vasodilation is of peripheral origin.

Adult↗
PubMed2002

Neural signal processing: the underestimated contribution of peripheral human C-fibers.

The microneurography technique was used to analyze use-dependent frequency modulation of action potential (AP) trains in human nociceptive peripheral nerves. Fifty-one single C-afferent units (31 mechano-responsive, 20 mechano-insensitive) were recorded from cutaneous fascicles of the peroneal nerve in awake human subjects. Trains of two and four suprathreshold electrical stimuli at interstimulus intervals of 20 and 50 msec were applied to the receptive fields of single identified nociceptive units at varying repetition rates. The output frequency (interspike interval) recorded at knee level was compared with the input frequency (interstimulus interval) at different levels of accumulated neural accommodation. At low levels of use-dependent accommodation (measured as conduction velocity slowing of the first action potential in a train), intervals between spikes increased during conduction along the nerve. At increasing levels of neural accommodation, intervals decreased because of a relative supernormal period (SNP) and asymptotically approached the minimum "entrainment" interval of the nerve fiber (11 +/- 1.4 msec) corresponding to a maximum instantaneous discharge frequency (up to 190 Hz). For neural coding, this pattern of frequency decrease at low activity levels and frequency increase at high levels serves as a mechanism of peripheral contrast enhancement. The entrainment interval is a good minimum estimate for the duration of the refractory period of human C-fibers. At a given degree of neural accommodation, all afferent C-units exhibit a uniform pattern of aftereffects, independent of fiber class. The receptive class of a fiber only determines its susceptibility to accommodate. Thus, the time course of aftereffects and existence or absence of an SNP is fully explained by the amount of preexisting accommodation.

Action Potentials↗
PubMed1999

Nociceptive neurons in the rat caudal trigeminal nucleus respond to blood plasma perfusion of the subarachnoid space: the involvement of complement.

The meninges of the brain are innervated by afferent nerve fibres containing SP and CGRP, two typical peptides found in sensory neurons. These fibres project to the trigeminal nuclear complex and the cervical dorsal horn. Discharge of the afferents may provide a physiological basis for some types of headaches. Considerable speculation surrounds the possible causes of meningeal afferent activation. Blood-borne substances released during subarachnoid haemorrhage are one possibility and there is a possibility that these also play a role in migraine. In the case of migraine, blood components, e.g. from platelets, cannot be excluded. To investigate the possible effects of platelets and plasma factors, the subarachnoid space of the rat was continuously perfused with artificial cerebrospinal fluid during extracellular recordings from single units of the caudal trigeminal nucleus. Washed and concentrated suspensions of adenosindiphosphate (ADP)--activated platelets and plasma, from which platelets had been removed--were introduced as a bolus into the continuous flow. Neurons in the caudal nucleus of the trigeminal complex receiving input from the meninges were stimulated. They did not respond to the activated platelet suspensions but showed intense responses to plasma. Plasma completely lost its ability to excite trigeminal neurons after heat inactivation (30 min, 56 degrees C). It is concluded that the complement system may be involved in the excitatory nociceptive effect of platelet-poor plasma.

Animals↗
PubMed1998

Sympathetic vasoconstrictor reflex pattern in patients with complex regional pain syndrome.

Twenty patients suffering from complex regional pain syndrome (CRPS) and 21 healthy control subjects were examined to evaluate sympathetic reflex vasoconstriction. The mean age of the 12 female and eight male patients was 48.9 (21-72) years. At the time of investigation the median duration of the disease was 8.5 weeks (2-70). Twenty-one healthy subjects were investigated for control. Different maneuvers, such as the veno-arteriolar reflex (VAR), inspiratory gasp (IG), cold pressor test (CP) and mental arithmetic (MA), were employed to induce vasoconstriction while the cutaneous blood flow of the affected and the contralateral limb was recorded. In addition, the skin temperature of both limbs was measured by infrared thermography. In 14 of 20 patients and in 14 of 21 control subjects vasoconstriction due to the provocation tests could be measured, while the remaining six patients and seven controls showed vasodilatation in at least one test, and by that they were excluded from analysis of vasoconstrictor reflex pattern. After thermoregulatory adaptation skin temperature was not different between the affected and the unaffected limb. Sympathetic reflex vasoconstriction triggered by MA which represents cortical generated, moderate vasoconstrictor stimulus, was significantly reduced on the affected limb (102.9% of prestimulus period) when compared to the control limb (85.0%, P < 0.002) or to controls (84.8%, P < 0.001). VAR (pure postganglionic), IG and CP (both spinal and supraspinal), representing stronger vasoconstrictor stimuli, revealed no significant side to side difference of sympathetic vasoconstriction and no significant difference as compared to controls. In conclusion our findings prove impairment of sympathetic vasoconstrictor activity after central vasoconstrictor stimulation in CRPS, and possible mechanisms are discussed.

Adult↗
PubMed1992

Psychophysical examination of pain induced by defined CO2 pulses applied to the nasal mucosa.

In 12 volunteer subjects, noxious chemical stimulation was performed by applying precisely controlled CO2 pulses to the nasal mucosa. Each subject participated in 2 identical psychophysical sessions including: (1) determination of the pain threshold, (2) determination of stimulus response functions to different durations of CO2 pulses with fixed concentration and (3) determination of stimulus response functions to different concentrations of CO2. In this test we also examined the relative sensitivity of the visual analogue scale (VAS) and the magnitude estimation (ME) procedure. The reliability of the psychophysical data was tested by comparing the results obtained in both sessions. The intra-individual variability of the pain threshold was rather low. All the CO2 pulse widths used induced phasic pain sensations which when averaged encoded stimulus durations of up to 1 sec. Longer application periods did not further increase the pain sensations. The stimulus response functions to different concentrations of CO2 could be described well with Stevens' power functions. In our hands the VAS and ME procedures proved to be equally sensitive. The obtained psychophysical data appeared to be rather reliable since no significant differences in the ratings obtained in both sessions could be observed.

Adult↗
PubMed1991

A novel technique for the evaluation of mechanical pain and hyperalgesia.

We describe a new technique which is useful for the evaluation of mechanically induced pain and hyperalgesia. Light metal cylinders are guided and accelerated in a barrel. On impact against the skin they elicit a brief sensation of pain. This method allows the application of a wide range of controllable innocuous and noxious impact velocities of the cylinder at variable stimulus repetition rates. The system is sufficiently flexible to stimulate perpendicularly any skin area and to move rapidly to adjacent target regions if desired. Psychophysical testing using magnitude estimation techniques revealed that pain thresholds were normally distributed. Over a wide range of stimulation intensities monotonically increasing stimulus response functions were obtained. Repeated testing showed a good intra-individual reproducibility of both threshold and supramaximal pain ratings. The method was also useful in determining the time course of pain and mechanical hyperalgesia following a brief painful stimulus. We conclude that the new technique is useful for evaluating psychophysical stimulus response functions of mechanically induced pain and its changes following tissue injury. This technique may also hold some promise in quantifying altered pain sensitivity in patients.

Adult↗
PubMed1990

Pain and vascular reflexes in man elicited by prolonged noxious mechano-stimulation.

Interdigital webs of the hands of human volunteers were pinched for periods of 2 min duration to induce tonic pain perceptions. During stimulation, the subjects gave estimates of their pain level at 10-sec intervals on a visual analogue scale, and the stimulus induced changes of the skin blood flow in the stimulated hand was assessed by photo-plethysmography. Sustained pinching induced a tonic reflex vasoconstriction in the stimulated hand with rather slow adaptation rate and no signs of habituation between trials. Step increases of the pinching force in the course of a stimulus were reflected by a decrease in plethysmogram amplitude as well as by increased pain ratings, although the subjects were usually unaware of these steps. Lowering the stimulus strength induced opposite, albeit much smaller effects in both pain ratings and vascular reactions. It is concluded that the vasomotor responses described in this paper are mediated by nociceptor input and reflect the processing of this input mainly at a spinal level.

Blood Flow Velocity↗
PubMed1987

The effect of carrageenan-induced inflammation on the sensitivity of unmyelinated skin nociceptors in the rat.

Carrageenan was subcutaneously injected in the area innervated by the saphenous nerve. Part of the mechano-heat sensitive C-fiber receptors (CHM) located inside or at the border of the inflamed area showed an enhanced responsiveness to heat stimulation (sensitization). Those CMH units exhibited spontaneous activity; their mechanical thresholds (von Frey) were higher than those of not spontaneously active fibers. None of the units located outside of the inflamed area displayed sensitization. The data reveal that only part of the CMH units in a uniformly inflamed skin area shows signs of sensitization. Our results are compared to those obtained in other inflammatory processes. The relation to inflammatory pain and to hyperalgesia and the contribution of endogenous substances to sensitization of CMH units are discussed.

Animals↗