Complex regional pain syndrome--are we neglecting neglect?
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Comment↗
Biomedical subjects
Jörn Schattschneider
Publications and source records attributed to Jörn Schattschneider.
Behavioral and sensory changes after direct ischemia-reperfusion injury in rats.
Complex regional pain syndromes (CRPS) are disabling pain syndromes that can develop after trauma or minor tissue injury affecting a limb. Characteristics of CRPS are sensory signs and symptoms, autonomic abnormalities, trophic changes and an impaired motor function. Pathophysiological mechanisms for the development of CRPS are still a matter of investigation. Based on clinical data and investigations of CRPS patients it is hypothesized that tissue hypoxia and inflammation are important for the development of CRPS. The aim of the current study was therefore to examine if direct ischemia-reperfusion injury can induce behavior in rats with symptoms present in patients with CRPS. After baseline behavior measurements the femoral artery of Wistar rats was ligated for 3h with consecutive reperfusion. Sham-operated rats underwent the same preparation except ligation of the artery. Subsequent behavioral testing (observations of spontaneous pain behavior, paw withdrawal to mechanical, noxious mechanical, cold and heat stimuli) was performed up to two months after surgery. Both in rats that underwent ischemia and in sham-operated rats no obvious changes of hindpaw tissue were observed after ischemia-reperfusion injury (trophic changes, edema, differences in skin color or temperature). In behavioral tests only minor changes were observed, these being not different between postischemic rats and sham-operated rats. Using Wistar rats, our data do not support the idea that an ischemia-reperfusion injury can play a major role in the development of CRPS.
Animals↗
Prolonged maintenance of capsaicin-induced hyperalgesia by brief daily vibration stimuli.
This study tests the hypothesis that central sensitization initiated by nociceptive input can be maintained by repeated brief innocuous peripheral inputs. Capsaicin was injected intradermally into the hind paw of adult rats. Three different types of daily cutaneous mechanical stimulations (vibration, soft brush, or pressure) were applied to the capsaicin-injected paw for a period of 2 weeks. Daily stimulation consisted of a 10-s stimulation repeated every 30s for 30 min. Foot withdrawal thresholds to von Frey stimuli applied to the paw were measured once a day for 4 weeks. The capsaicin-only group (control rats without daily stimulation) showed hyperalgesia lasting for 3 days. In contrast, hyperalgesia persisted for 2 weeks in the group that received vibration stimulation. Neither the soft brush nor the pressure group showed a significant difference in mechanical threshold from the control group (capsaicin only). The vibration-induced prolonged hyperalgesia was significantly reduced by systemic injection of ifenprodil, an NMDA-receptor antagonist, but it was not influenced by either an AMPA-receptor blocker or a reactive oxygen species (ROS) scavenger. Furthermore, a dorsal column lesion did not interfere with the prolongation of hyperalgesia. Data suggest that vibration-induced prolongation of hyperalgesia is mediated by spinal NMDA-receptors, and a similar mechanism may underlie some forms of chronic pain with no obvious causes, such as complex regional pain syndrome type 1 (CRPS-1).
6-Cyano-7-nitroquinoxaline-2,3-dione↗
No adrenergic sensitization of afferent neurons in painful sensory polyneuropathy.
INTRODUCTION: The aim of the present study was to determine (1) if an adrenergic sensitivity of afferent neurons is present in patients with painful polyneuropathy as compared with non-painful polyneuropathy and (2) if there is a correlation between adrenergic sensitisation and the severity of afferent and sympathetic small fiber damage. METHODS: 10 patients with painful and non painful polyneuropathy and 10 healthy controls were included. The function of small afferent and efferent sympathetic neurons was evaluated. Adrenergic sensitivity of afferent neurons was assessed by cutaneous iontophoresis of norepinephrine. Spontaneous pain, mechanical hyperalgesia as well as warm and heat pain thresholds were measured. RESULTS: Iontophoresis of norepinephrine did not induce or enhance spontaneous pain or mechanical allodynia, either in painless or painful polyneuropathies. There was no difference in norepinephrine-induced heat hyperalgesia between both neuropathy groups and healthy controls. The response of afferent neurons to norepinephrine was not correlated with the severity of damage to afferent small fibers or efferent sympathetic vasoconstrictor neurons. CONCLUSION: The results do not support the assumption that in painful polyneuropathies afferent neurons acquire an adrenergic sensitivity after nerve injury and that adrenergic stimulation leads to an exacerbation of spontaneous pain and thermal and mechanical hyperalgesia.
Aged↗
Postherpetic neuralgia: topical lidocaine is effective in nociceptor-deprived skin.
OBJECTIVES: Topical lidocaine is effective in postherpetic neuralgia (PHN). The aim of the present investigation was to classify patients according to their predominant peripheral nociceptor function and to compare these data with the results of a controlled study using dermal lidocaine patch. METHODS: Within the skin area of maximal pain QST (thermotest) and QCART (histamine iontophoresis and laser Doppler flowmetry) were performed prospectively in 18 PHN patients. A controlled study using cutaneous lidocaine (lidocaine 5% patch, IBSA) followed. RESULTS: Six patients (group I, sensitised nociceptors) had no sensory loss. Heat pain thresholds were equal or lower than on the contralateral side. Histamine-induced flare and axon reflex vasodilatation were not different on both sides. Histamine evoked pain increased. In 12 patients (group II, nociceptor impairment) heat pain thresholds were higher than contralateral. Histamine-induced flare was impaired or abolished. Histamine did not induce any sensation. Lidocaine was efficacious in the entire group of patients. Subgroup analysis revealed that patients with impairment of nociceptor function had significantly greater pain reduction under lidocaine vs placebo. Patients with preserved and sensitised nociceptors demonstrated no significant pain relief. CONCLUSIONS: PHN patients differ concerning their cutaneous nociceptor function: In the group I pain is caused by pathologically sensitised nociceptors. In subset II there is a loss of function of cutaneous C-nociceptors within the allodynic skin. Patients responded well to topical lidocaine even if the skin was completely deprived of nociceptors. Different underlying mechanisms of lidocaine action in nociceptor-deprived skin are discussed.
Administration, Cutaneous↗
Harlequin syndrome--one face of many etiologies.
BACKGROUND: A 55-year-old woman presented to hospital with a 3-month history of asymmetric facial flushing of the skin during exertion, and an 18-month history of left-sided ptosis and miosis. Detailed medical history analysis revealed that a palpable node measuring 0.8 x 1.2 x 1.2 cm (volume 1.1 ml) had been discovered 2 years previously, within the left lobe of an otherwise uncomplicated goiter that had been successfully managed for 20 years. Otherwise, the patient was healthy. INVESTIGATIONS: Neurological examination, autonomic testing, duplex ultrasonography, scintigraphy and MRI. DIAGNOSIS: Harlequin syndrome following a lesion of the preganglionic sympathetic efferents, caused by neurovascular compression of the sympathetic chain between the stellate and superior cervical ganglion brought about by an elongated inferior thyroid artery. MANAGEMENT: Explanation of pathophysiology and benign nature of the condition.
Autonomic Nervous System Diseases↗
Topical menthol--a human model for cold pain by activation and sensitization of C nociceptors.
Although cold hyperalgesia is a frequent symptom in patients with neuropathic pain, it is poorly understood. We investigated the mechanisms of cold pain by studying the effect of menthol on pain, temperature perception, touch sensation and skin perfusion. In 10 subjects, 40% l-menthol, and ethanol, serving as control, were topically applied to the forearm in a double-blinded two-way crossover study. Menthol induced significant pain and cold sensations, punctate and cold hyperalgesia and an increase in cutaneous perfusion. Other mechano-sensory and thermal tests were unchanged (touch, cold and warm detection thresholds, heat pain threshold; no dynamic and static hyperalgesia, no wind-up). To investigate the underlying mechanisms, the effects of menthol versus ethanol on the dorsum of the hand were tested during A fibre conduction blockade of the superficial radial nerve in another 10 subjects. The block itself led to hypoaesthesia for mechanical stimuli and anaesthesia for cold perception, but induced an increase in cold-mediated pain. This was due to lack of inhibition of C nociceptors normally exerted by concomitant activation of A fibres. Under these conditions, menthol-induced cold sensation and punctate hyperalgesia were abolished. However, menthol induced spontaneous pain with a trend to higher values than without block. Furthermore, the hyperalgesia to cold stimuli, that was already present during A fibre block, was further increased significantly by menthol. We suggested that menthol acts to sensitize cold-sensitive peripheral vasoactive C nociceptors and activates cold-specific A delta fibres. Punctate hyperalgesia is due to central sensitization based on the ongoing activity in the sensitized cold-sensitive peripheral C nociceptors. In conclusion, topical menthol is a human model for cold pain by exposing for the first time the mechanism of sensitized peripheral cold C nociceptors that may also be involved in neuropathic pain.
Administration, Topical↗
Idiopathic restless legs syndrome: abnormalities in central somatosensory processing.
OBJECTIVES: Neurophysiological studies have shown an impairment of temperature perception in secondary and idiopathic restless legs syndrome (RLS). It is unclear whether these deficits are caused by peripheral nerve fibre damage or by central impairment of somatosensory processing. The aim of the present study was (1) to determine the frequency of thermal hypaesthesia in a large population of secondary and idiopathic RLS patients; (2) to differentiate between a peripheral and central disturbance of somatosensory processing and (3) to correlate these findings with the clinical manifestation of the disease. METHODS: From the results of clinical examination, nerve conduction studies and blood samples the patients were divided into secondary and idiopathic RLS groups. The severity of RLS symptoms was assessed by standardized questionnaires. Quantitative sensory testing (QST) assessing temperature perception was performed in all patients. The peripheral function of small nerve fibres was evaluated by the quantitative nociceptor axon reflex test (QNART). RESULTS: 22 secondary and 20 idiopathic RLS patients participated in the study. Impairment of temperature perception (QST) was found in 72% of the secondary RLS patients and in 55% of idiopathic RLS patients. The peripheral C-fibre function (QNART) was normal in idiopathic RLS patients. In contrast it was significantly impaired in secondary RLS patients compared with idiopathic RLS patients and age matched controls. There was no correlation between the results obtained in QST and clinical scores. CONCLUSION: Impairment of temperature perception is present in a high percentage of RLS patients. In secondary RLS the sensory deficits are at least in part caused by small fibre neuropathy. In idiopathic RLS a functional impairment of central somatosensory processing is present.
Blood Flow Velocity↗
Effect of sympathetic muscle vasoconstrictor activity on capsaicin-induced muscle pain.
Neuropathic pain syndromes with sympathetically maintained pain are often associated with a deep somatic pain component. An adrenergic interaction between sympathetic vasoconstrictor neurons and cutaneous afferents has been demonstrated. To determine whether a sympathetic-afferent interaction exists in deep somatic tissues, we investigated the effect of sympathetic muscle vasoconstrictor activity on experimentally induced pain. In 12 healthy volunteers, capsaicin was infused into the anterior tibial muscle. Intensity and quality of muscle and referred pain were assessed. The analyses were performed during the presence of low sympathetic muscle vasoconstrictor activity induced by breathing 100% O(2) gas (normocapnia), and during high activity induced by inspiration of 95% O(2) and 5% CO(2) (hypercapnia). The degree of sympathetic muscle vasoconstrictor discharge was monitored indirectly by measuring systemic blood pressure and end-expiratory CO(2) and by performing duplex sonography of muscle resistance vessels. The intensity, quality, and spatial distribution of muscle and referred pain were not significantly different during resting and increased sympathetic muscle vasoconstrictor discharge, indicating that such activity does not influence pain after intramuscular infusion of capsaicin.
Adult↗
Skin temperature side differences--a diagnostic tool for CRPS?
Complex regional pain syndrome type I (CRPS I) is a chronic painful disease of one extremity that may develop as a disproportionate consequence of a trauma affecting the limbs without overt nerve injury. It is clinically characterized by sensory, motor and autonomic symptoms including vascular abnormalities. Previously, we have reported that pathophysiological alterations of the ongoing sympathetic activity play a crucial role in vasomotor disturbances (Brain 124 (2001) 587). As a companion article, the aim of this study was to evaluate the diagnostic value of skin temperature side differences in consideration of the spontaneous sympathetic vasoconstrictor activity. Twenty-five patients with CRPS I were studied. Fifteen patients with painful limbs of other origin and 20 healthy individuals served as controls. Controlled thermoregulation was performed to change cutaneous sympathetic vasoconstrictor activity by the use of a thermal suit: skin sympathetic vasoconstrictor neurones were activated by whole-body cooling and nerve activity was abolished by whole-body warming. Skin temperature at the affected and unaffected limbs (infra-red thermometry) was measured under resting conditions and continuously monitored during controlled modulation of sympathetic activity. The results showed only minor skin temperature asymmetries between both limbs under resting conditions in most CRPS patients. However, during controlled thermoregulation temperature differences between both sides increased dynamically and were most prominent at a high to medium level of vasoconstrictor activity. In both control groups, there were only minor side differences in temperature both in rest and during thermoregulatory changes of sympathetic activity. When comparing the diagnostic value of skin temperature asymmetries in CRPS I, sensitivity was only 32% under resting conditions, but increased up to 76% during controlled alteration of sympathetic activity. Specificity was 100% at rest and 93% at controlled thermoregulation. We concluded that the degree of unilateral vascular disturbances in CRPS I depends critically on spontaneous sympathetic activity. Taking this into consideration, skin temperature differences in the distal limbs are capable of reliably distinguishing CRPS I from other extremity pain syndromes with high sensitivity and specificity.
Adult↗
Docetaxel-induced nail changes--a neurogenic mechanism: a case report.
Docetaxel is a new taxoid widely used in chemotherapy for advanced breast cancer and other solid malignancies. Painful nail changes with onycholysis occur in about 40% of docetaxel-treated patients as a prominent adverse effect. We report a patient with a complete peripheral palsy of the right arm due to advanced breast cancer with diffuse tumor infiltration of the brachial plexus. Treatment with docetaxel led to onycholysis at all extremities except the paretic hand. Sensory and motoric innervation measured by nerve conduction studies showed a complete loss of large nerve fiber function of the right arm. Function of deep mechanosensitive A beta-fibers (quantitative vibrametry) was severely decreased, but not absent. Sympathetic reflexes (induced by deep inspiration and measured with laser Doppler flowmetry) were absent on the right side and skin temperature was decreased consistent with a complete sympathetic denervation. Small afferent fibers investigated by quantitative thermotesting revealed a total loss of thermal and pain sensation. Furthermore, iontophoresis of histamine failed to induce any axon reflex-vasodilatation indicating a complete peripheral degeneration of small fiber afferents. In summary, a severe denervation of small and large fibers of the right upper limb was revealed. These results indicate that integrity of peripheral nerves seems to be a substantial factor for docetaxel-mediated nail changes. The role of an inflammatory process in onycholysis maintained by postganglionic sympathetic terminals and nociceptive C-fiber afferents is discussed. In accordance with this hypothesis, a cyclooxygenase-2 inhibitor improved nail alterations of the non-paretic limbs.
Afferent Pathways↗
Complex regional pain syndromes: the influence of cutaneous and deep somatic sympathetic innervation on pain.
OBJECTIVES: Complex regional pain syndromes (CRPS) can be relieved by sympathetic blockade. Different sympathetic efferent output channels innervate distinct effector organs (ie, cutaneous vasoconstrictor, muscle vasoconstrictor. and sudomotor neurons, as well as neurons innervating deep somatic tissues like bone, joints, and tendons). The aim of the present study was to elucidate in CRPS patients the sympathetically maintained pain (SMP) component that exclusively depends on cutaneous sympathetic activity compared with the SMP depending on the sympathetic innervation of deep somatic tissues. METHODS: The sympathetic outflow to the painful skin was modulated selectively in awake humans. High and low cutaneous vasoconstrictor activity was produced in 12 CRPS type 1 patients by whole-body cooling and warming (thermal suit). Spontaneous pain was quantified during high and low cutaneous vasoconstrictor activity. By comparing the cutaneous SMP component with the change in pain that was achieved by modulation of the entire sympathetic outflow (sympathetic ganglion block), the SMP component originating in deep somatic structures was estimated. RESULTS: The relief of spontaneous pain after sympathetic blockade was more pronounced than changes in spontaneous pain that could be induced by selective sympathetic cutaneous modulation. The entire SMP component (cutaneous and deep) changes considerably over time. It is most prominent in the acute stages of CRPS. CONCLUSIONS: Sympathetic afferent coupling takes place in the skin and in the deep somatic tissues, but especially in the acute stages of CRPS, the pain component that is influenced by the sympathetic innervation of deep somatic structures is more important than the cutaneous activation. The entire sympathetic maintained pain component is not constant in the course of the disease but decreases over time.
Adult↗