Bilateral motor cortex disinhibition in complex regional pain syndrome (CRPS) type I of the hand.

BACKGROUND: Complex regional pain syndrome type I (CRPS I) develops as a consequence of trauma affecting the limbs, without obvious nerve lesion. Its features include pain, edema, autonomic dysfunction, movement disorder, and trophic changes. CNS involvement is suggested by the symptoms, but the pathophysiology of CRPS I is unknown. OBJECTIVE: To assess excitability changes in the motor cortex in patients with CRPS I. METHODS: The authors studied 25 patients with unilateral CRPS I involving the hand by means of transcranial magnetic stimulation using a paired-pulse paradigm. Motor threshold (MT) and intracortical inhibition and facilitation were determined on the affected and the clinically unaffected side. A control group of 20 healthy subjects was studied. RESULTS: The authors found a significant reduction of intracortical inhibition on both sides of patients with CRPS compared with control subjects, whereas intracortical facilitation and MT did not differ significantly. However, in the patients' group, the presence of allodynia significantly decreased MT. CONCLUSIONS: The authors showed a bilateral disinhibition of the motor cortex in patients with complex regional pain syndrome.

NMDA-mediated mechanisms in cortical excitability changes after limb amputation.

OBJECTIVES: The aim of our study was to determine the role of N-methyl-d-aspartate (NMDA)-mediated mechanisms in cortical excitability changes after limb amputation, and their possible relationship to phantom pain. MATERIALS AND METHODS: Sixteen upper limb amputees who were suffering from chronic phantom pain received the NMDA-antagonist memantine or placebo for 3 weeks. Intracortical inhibition (ICI) and intracortical facilitation (ICF) were determined at baseline and on day 21 using transcranial magnetic stimulation. Simultaneously, phantom pain intensity was assessed. RESULTS: Memantine reduced ICF and enhanced ICI to roughly the same extent as seen in healthy subjects in a previous study. These changes were not correlated to the reduction of phantom pain. CONCLUSION: We therefore conclude that NMDA-mediated mechanisms influence changes of ICI and ICF occurring after limb amputation. However, our results suggest that these cortical excitability changes and phantom pain are independent of each other.

Assessment of reorganization in the sensorimotor cortex after upper limb amputation.

OBJECTIVE: We wanted to investigate plastic changes occurring in the motor and somatosensory cortex after upper limb amputation, and their possible relationship to phantom pain. METHOD: To assess these plastic changes, we used transcranial magnetic stimulation (TMS) and source localization of somatosensory evoked potentials (SEP). Eleven patients with upper limb amputation were investigated. The phantom pain intensity was assessed by visual analogue scaling (VAS). RESULTS: Using TMS mapping, we found a significant lateralization of the amplitude-weighted centre of gravity (P<0.01) and an enlargement of the excitable area (P<0.05) on the hemisphere contralateral to the amputation. SEP mapping showed a significant medialization of the N20 dipole (P<0.05) on this side. None of these changes correlated with the phantom pain intensity. CONCLUSIONS: We conclude that after limb amputation, the relationship between plastic changes occurring in the sensorimotor cortex and phantom pain seems to be more complex than previously believed.

Changes of cortical excitability in patients with upper limb amputation.

In our study we wanted to assess motor excitability in patients with upper limb amputation by means of transcranial magnetic stimulation (TMS). In 12 patients, TMS was applied using a paired pulse paradigm in order to test cortico-cortical excitability. Additional parameters of motor excitability like motor threshold and cortical silent period were also measured. Recordings from the amputated side were compared to the contralateral side and to healthy controls. We found a significant reduction of intracortical inhibition in forearm amputees and an enhancement of intracortical facilitation in upper arm amputees on the affected side. We conclude that after upper limb amputation, changes in the activity of intracortical interneuronal circuits appear in the affected hemisphere. These changes may depend on the level of amputation, and be the base of cortical reorganization.

Influence of the N-methyl-D-aspartate antagonist memantine on human motor cortex excitability.

The aim of our study was to investigate the effect of the N-methyl-D-aspartate (NMDA) antagonist memantine on motor excitability in humans. Seven healthy volunteers received memantine or placebo, respectively, over a period of 8 days. At day 8, transcranial magnetic stimulation (TMS) was performed using a paired pulses paradigm in order to assess intracortical inhibition and facilitation. Additionally, motor threshold and silent period duration after TMS were measured as well as M waves, F waves and peripheral silent period after electrical peripheral nerve stimulation. Intracortical inhibition was enhanced, and intracortical facilitation reduced after memantine ingestion in comparison to placebo, whereas no significant difference could be observed regarding the other neurophysiological parameters. We conclude that the NMDA receptor is involved in the regulation of excitability of intracortical interneuronal circuits.

[Posttraumatic pain. Causes and therapeutic possibilities]. / Posttraumatische Schmerzen. Ursachen und Therapiemöglichkeiten.

Each patient has the right of a dedicated pain therapy according to the state of the art. However an efficient pain therapy is not possible without knowing the cause of pain. In most posttraumatic pain situations peripheral nociceptors are activated and normal afferences are conducted via an intact nociceptive system. In contrast, neuropathic pain pain is caused by lesions of the nervous system itself. Mechanisms of central sensibilization and involvement of the sympathetic nervous system may lead to chronification of such pain conditions. The therapeutic regime of nociceptive and neuropathic pain is demonstrated by algorithms of treatment modalities. Apart from classic non-opioid analgesics, co-analgesics and opioids have an important status in chronic pain management as well. Prescription of these substances has to follow strictly defined standards of pain therapy. Blockades with local anaesthetics as mono-therapy of chronic pain are obsolete. In posttraumatic pain, however, a certain number of adjuvant blockades or infiltrations of triggerpoints may be helpful. The exceptional place of sympathetic blockades are in diagnosis and therapy of sympathetic maintained pain (SMP).

Hemisensory impairment in patients with complex regional pain syndrome.

The purpose of the present study was to investigate the extent and quality of sensory impairment and their relation to pain characteristics and movement disorders in patients suffering from complex regional pain syndrome (CRPS) type I. Neurological testing was performed independently by two examiners in 24 patients with CRPS type I. In eight patients (33%), a hemisensory impairment with decreased temperature and pinprick sensation ipsilateral to the limb affected by CRPS could be observed. In four patients (17%), a sensory deficit in the upper quadrant of the body could be demonstrated and in eight patients (33%), sensory impairment was limited to the limb affected by CRPS. Mechanical allodynia and mechanical hyperalgesia could be observed in a higher percentage of patients with hemisensory deficit or sensory impairment in the upper quadrant (92%), than in those patients with sensory impairment limited to the affected limb (17%) (P < 0.005). In patients with left-sided CRPS, sensory abnormalities in the upper quadrant or hemisensory impairment were more frequently demonstrated (77%) than in patients with right-sided CRPS (18%) (P < 0.005). There was a high correlation (92%) for the sensory findings between the two examiners, and hemisensory abnormalities were stable over a period of 3-6 months in all six patients with repeated examinations. Motor impairment (contractures, weakness, tremor or difficulties in initiating movement) could be observed in a higher percentage in patients with sensory abnormalities in the upper quadrant or hemisensory impairment (83%) than in patients with sensory impairment limited to the affected limb (42%) (P < 0.05) and was significantly correlated with allodynia/hyperalgesia (P < 0.005). The results demonstrated that sensory deficits in patients with CRPS, frequently extend past the painful area of the affected limb. The increased frequency of mechanical allodynia and movement disorders in patients with hemisensory impairment or sensory deficits in the upper quadrant, might indicate that central mechanisms are involved in the pathogenesis of CRPS in these patients.

Post-traumatic pain. Causes and therapeutic concepts.

Each patient has the right of a dedicated pain therapy according to the state of the art. However an efficient pain therapy is not possible without knowing the cause of pain. In most posttraumatic pain situations peripheral nociceptors are activated and normal afferences are conducted via an intact nociceptive system. In contrast, neuropathic pain pain is caused by lesions of the nervous system itself. Mechanisms of central sensibilization and involvement of the sympathetic nervous system may lead to chronification of such pain conditions. The therapeutic regime of nociceptive and neuropathic pain is demonstrated by algorithms of treatment modalities. Apart from classic non-opioid analgesics, co-analgesics and opioids have an important status in chronic pain management as well. Prescription of these substances has to follow strictly defined standards of pain therapy. Blockades with local anaesthetics as mono-therapy of chronic pain are obsolete. In posttraumatic pain, however, a certain number of adjuvant blockades or infiltrations of triggerpoints may be helpful. The exeptional place of sympathetic blockades are in diagnosis and therapy of sympathetic maintained pain (SMP).

Experiences with the prescription of opioids: a patient questionnaire.

Forty-three German patients who had been treated with strong opioids were questioned about their experiences during therapy. The prescription of opioids was well accepted by most patients. Some, however, felt stigmatized by taking opioids. Fourteen patients (33%) were asked by their relatives, friends, or other patients about the special prescription form. Six patients (14%) had difficulties in redeeming the prescription at the pharmacy, seven patients (16%) were warned against taking the medication by the pharmacist, 21 patients observed that their general practitioner (GP) was mistrustful about the treatment, and 16 patients (37%) reported that the GP terminated the therapy. Despite the beneficial effect for the patient, opioid treatment started and supervised in a pain clinic is not always continued by the GP. In Germany, it may not be possible to administer opioid therapy outside of a specialized pain clinic. In those few cases in which an opioid therapy is successfully instituted, difficulties continue due to prejudices, insufficient education, and complicated prescription laws.

[Sympathetic reflex dystrophy and phantom pain. Diagnosis, therapy and prognosis]. / Sympathische Reflexdystrophie und Phantomschmerz. Diagnostik, Therapie und Prognose.

The incidence of phantom limb pain has been significantly underestimated for many years. However, studies published during the recent decade indicate that the real incidence of phantom limb pain may be between 60% and 90%. Reflex sympathetic dystrophy (RSD) occurs with an incidence of about 15.000 new cases every year in Germany. Both diseases show early centralisation and chronification. Hence, only early diagnosis and onset of correct therapy in time provide significant pain reduction. When therapy is started too late, prognosis in regard to sufficient pain reduction is poor. Phantom limb pain can be prevented by proper anaesthesia. Several studies could show the benefit of perioperative continuous regional anaesthesia . None of the patients treated with a combination of local anaesthetics and low dose morphine developed phantom limb pain. Therapy of choice for RSD is the sympathetic blockade. The most suitable method is intravenous regional sympathetic blockade (IVRSB) with guanethidine (2).

[A survey of physicians' knowledge about pain therapy with strong opioid analgesics]. / Befragung schmerztherapeutisch interessierter Arzte zur Verschreibung starker Opioidanalgetika.

INTRODUCTION: The WHO analgesic ladder, including the use of strong opioid analgesics for the treatment of cancer pain, is widely accepted. However, the use of opioids for the treatment of non-cancer pain is still controversial. This study investigates doctors' medical knowledge about basic aspects of pain management. Additionally, we determined whether the deficiencies in the treatment of patients suffering from pain are based on the rigorous national narcotic control system in Germany. METHODS: We investigated the juridical and technical knowledge of physicians specializing in pain therapy by a questionnaire. During a postgraduate course the knowledge about pain therapy according to the WHO analgesic ladder and the beliefs concerning the narcotic regulations in Germany were evaluated. The survey participants were asked to rate their attitudes on a 10-point analogue scale (1=disagreement, 10=full agreement). The participants were also asked to indicate occupational criteria such as specialty, clinical practice area, and postgraduate years of practice. Descriptive statistics for the mean values were used. RESULTS: One hundred and forty-three questionnaires were completed. The majority of participants worked at departments of anaesthesiology. Some 51.1% of the participants had no specific multiple-copy prescriptions for opioid analgesics. Only 72% of the physicians knew from which governmental institution they could order multiple-copy prescriptions. In general, more doctors would prescribe opioids by the use of normal forms. The controlled substance laws were seen as an impediment by the majority of participants, without relevant differences as to their years of practice. The regulations were regarded as ineffective protection against illegal use of opioids. Treatment of pain with strong opioid analgesics was seen as beneficial for the patients. The use of strong opioids for long-term treatment was recommended, and psychological addiction was regarded as non-existent. CONCLUSION: Therapy with strong opioids is accepted practice, but significant deficits of legal and technical knowledge uphold the undertreatment of patients suffering from cancer and non-cancer pain. Patients with a legitimate need for pain relief by strong opioids are the unintended victims of tight narcotic regulations and deficits in medical education. An ease of regulatory conditions is mandatory to reduce the reluctance for prescribing opioids. On the other hand intensified continuous medical education is mandatory to reduce the undertreatment of patients with severe pain conditions.

Long-term effects of nerve blocks in chronic pain.

Regional blockade techniques have been of crucial importance for decades in chronic pain therapy, but in recent years some developments have made a new definition of the status of invasive procedures necessary. The realization of chronic pain as a multifactorial process led to the establishment of an interdisciplinary approach to pain therapy, leaving blockades as only one step in a multimodal therapy. The mainstay of local anaesthetic blocks now is diagnostic and prognostic, but correct interpretation of the results is limited by different factors, and controlled studies on the diagnostic value of local anaesthetic blockade are lacking. In cancer pain, invasive procedures are necessary in only a few cases. Some neuroablative techniques can offer long-term pain reduction. In non-cancer pain, neurodestructive procedures should be reserved for some special indications (e.g. lumbar sympathetic neurolytic blocks in ischaemic diseases). In a great number of chronic pain conditions the sympathetic nervous system is involved or even has a central status. In the acute stage of these diseases sympathetic blockades can be the therapy of choice. There is no disease in which different invasive procedures are performed so frequently and so uncritically as in chronic low back pain. Up to now, however, all controlled studies of invasive procedures only demonstrated short-term effects and failed to prove long-term efficacy. Therefore any invasive technique should only be performed in well-selected patients over a defined period and with a limited number of blockades.

[Opioids and driving ability]. / Opioide und Fahrtüchtigkeit.

INTRODUCTION: Clinical observations of patients under oral opioid treatment suggest that the initially appearing central side effects such as sedation, dizziness or drowsiness decrease after a few weeks of treatment. However, it is still unclear whether long-term treatment with opioids impairs complex psychomotor functions such as driving a car. METHODS: Twenty patients on stable dosages of oral opioids were examined using a driving simulator. The patients were regular car drivers and not older than 70 years. Additionally, every patient had to complete a questionnaire for mental condition and vigilance and the "d II" letter cancellation task. Control groups tested in the same way were: patients before an elective operation after taking benzodiazepines for sedation, volunteers after alcohol consumption (0.80 per thousand ), physicians on call with less than 4 h of sleep and healthy volunteers without any medication. RESULTS: Some of the patients treated with opioids reacted as fast as medication-free volunteers. There were no significant differences between the reaction times of older patients (>50 years) receiving opioids in comparison to the group of older healthy volunteers. The same result was obtained in the letter cancellation task. No differences could be seen between medication-free volunteers and patients receiving opioids with regard to tasks of visual or motor control skills. The volunteers under influence of alcohol and the patients under benzodiazepines had a considerable decrease in performance. CONCLUSIONS: Long-term therapy with opioids does not inevitably impair complex skills, but the decision to permit driving a car can only be made in the individual case. PRACTICAL RECOMMENDATIONS: At the beginning of therapy with opioids the physician has to fulfil his duty to inform the patient of any possible dangers of treatment. From the medical point of view, driving must be prohibited until a stable opioid dosage is reached. Any changes in dosage (increase, reduction), change of the opioid and poor general condition independent of the opioid therapy must result in prohibition of car driving. Continuous control of the therapy with documentation is a duty of the physician. The written documentation should include the patients' physical and mental condition, side effects and the therapeutic result. From the medical point of view, driving can be possible when dosage treatment and general condition remain stable. In any case, the doctor has to remind the patient of the responsibility of critical self-examination. In doubt, special performance investigation should be taken into consideration.

[Oral opioids for long-term treatment of chronic non-cancer pain]. / Orale Opioide zur Langzeittherapie chronischer Nicht-Tumorschmerzen.

The treatment of cancer pain with opioids is well accepted. However, the use of opioids for the treatment of non-cancer pain is still a matter of controversy. The main matters of concern are physical dependence and opioid abuse. Another argument against opioids is the lack of efficacy. Experiences with opioids in non-cancer pain have been published on about 850 patients, the longest therapy lasting almost 14 years. 85% of the patients treated with opioids had beneficial effects. In a number of investigations evaluating the opioid sensibility of pain by PCA and intravenous infusions, 67-80% of the patients with neuropathic pain responded to opioids. The efficacy of opioids in the treatment of non-cancer pain was proven in 3 placebo controlled studies. In 2 studies pain reduction in neuropathic pain was similar to that in nociceptive pain. When opioids are used, the administration has to be performed according to well defined standards. The indication for opioids must be made by a specialist in pain management. The diagnosis must clearly reveal an organic origin of the pain. Before the start of therapy the duration as well as the criteria for discontinuation must be set up. The treatment must be controlled by a specialist team and frequent regular follow up investigations must be performed. These must include proper documentation of the pain level, changes in patients' function and in social activities. The reliable intake of prescribed medication must be assured if necessary by laboratory screening. The treatment of non-cancer pain with opioids may be an alternative for those patients, who didn't gain sufficient reduction of pain by other therapies. Standards for this therapy are an absolute necessity and are to be followed closely.

[Dangers and complications in pain therapy with epidural and intrathecal catheters.]. / Gefahren und Komplikationen bei rückenmarknahen Katheterverfahren.

Pain therapy with epidural or intrathecal catheters is an invasive method. These techniques have specific indications in both acute and chronic pain therapy. However, complications can occur. Thus, the potential complications and the therapy necessary must be known.Drugs: Complications resulting from acute local anesthetic intoxication's are rare. High plasma levels during chronic therapy may lead to confusion. Respiratory depression can occur in opioid naive patients up to 12 (-24) h after injection. Adequate monitoring is a prerequisite for this therapy. After application of clonidine, hypotension is frequent in hypertonic and hypovolemic patients. Epidural or intrathecalcatheter placement can result in therapeutic failure, trauma by punction and inability to place the catheter. During chronic therapy, technical problems can occur, e.g., dislocation, occlusion. To exclude intrathecal and intravascular placement, application of a test dosage of a local anesthetic with adrenaline is recommended.Neurological complications can result in nerve root deficit or "simple" post-spinal headache, but cauda equina syndromes, paralyses, intracranial bleeding, sinus thrombosis and central neurological deficits have been reported. Skininfection at the insertion site of the catheter has been observed with an incidence of 1.9 to 7.7%. A spinal infection with neurological deficit is rare. Spinal infections are often associated with other diseases. Spinalhematomas are rare. Coagulation disorders and anticoagulants can lead to bleeding. Intravenous heparin should be avoided, because this is frequently associated with spinal bleeding. Therapy with cumarines is a contraindication for insertion of spinal catheters.Monitoring: During treatment with spinal catheters, adequate monitoring increases safety for the patients. Efficacy of the injections, puncture site and the neurological status should be documented daily. Neurological deficits must be diagnosed without losing time and adequate therapy must be initiated.

[Continuous sedation for regional anesthesia with propofol (Disoprivan) and midazolam (Dormicum). A comparative study]. / Kontinuierliche Sedierung zur Regionalanaesthesie mit Propofol (Disoprivan) und Midazolam (Dormicum). Ein Vergleich.

UNLABELLED: Propofol was compared to midazolam with regard to its quality as a sedative in regional anesthesia. 81 patients undergoing varicose-vein stripping under epidural anesthesia were divided into two groups: 39 were given propofol and 42 were given midazolam. Both groups were then subdivided into 3 subgroups. 30 min after epidural block, a bolus of propofol 1 mg/kg or midazolam 0.03 mg/kg was given followed by infusion of equipotent solutions: propofol 1.0, 1.5, or 2.0 mg/kg/h or midazolam 0.03, 0.045, 0.06 mg/kg/h. Continuous registration of blood pressure, respiratory rate, and end-expiratory pCO2 was carried out and blood gas analysis was performed every 30 min. RESULTS: Clinically unimportant changes of circulatory and respiratory parameters were seen. Blood gas analyses showed hypercapnia greater than 50 mmHg in some patients. Brief apnea occurred after bolus propofol in 7.7% of cases and pain during injection in 66.6%. Restlessness: propofol 28.2%, midazolam 9.5%. Upper airway obstruction: propofol 30.8%, midazolam 57.1%. Recovery time after infusion ranged from 130 s with propofol to 26 min with midazolam. Postoperative evaluation included the following questions and responses: Sedation pleasant? propofol 97.5%, midazolam 100%. Sleep during surgery? propofol 94.8%, midazolam 83.5%. Prolonged tiredness? propofol 25.6%, midazolam 69%. Postoperative nausea? propofol 38.5%, midazolam 14.2%. Vomiting? propofol 17.9%, midazolam 11.9%. Our study showed that propofol is highly suitable as a sedative for regional anesthesia in spite of injection pain and frequent postoperative nausea. It is superior to midazolam because of the significantly shorter recovery time, providing improved control-lability and reduced posthypnotic sleep.