Roman Dertwinkel

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.

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.

Efficacy of the NMDA-receptor antagonist memantine in patients with chronic phantom limb pain - results of a randomized double-blinded, placebo-controlled trial

&NA; Phantom limb pain (PLP) associated neuroplastic changes are partly mediated by excitatory amino acids at NMDA receptor sites. This study was undertaken to deduce if NMDA‐receptor antagonists may be effective in patients with chronic PLP. Therefore a four week double‐blinded, randomized placebo‐controlled trial was performed to evaluate the efficacy of 30 mg memantine/day, an orally administrable NMDA receptor antagonist. Thirty‐six patients, 18 per group, with a history of at least 12 months PLP and an average pain of at least 4 on the 11‐point numeric rating scale (NRS) were enrolled. The patients completed a standardized questionnaire before the trial. PLP intensity and the level of eight complaints were assessed during the trial. Number needed to treat (NNT) was calculated based on the average PLP during the 3rd week (steady state). In both groups, PLP declined significantly in comparison with the baseline (verum: 5.1 (±2.1) to 3,8 (±2,3), placebo from 5.1 (±2.0) to 3.2 (±1,46) NRS) without a re‐rising of the PLP during the washout period. Mean pain relief was 47% in the memantine group (10 patients reported more than 50% relief), 40% in the placebo group (6>50%): NNT were 4.5 (KI: 2.1–10.6). Analysis of covariance demonstrated a significant impact only on the prior PLP intensity, but no treatment effect. Two patients have demonstrated long‐term pain relief under memantine until now (16 months). The total number of slight adverse events were comparable in both groups, but the overall number of severe events was higher in the memantine group (P<0.05). This trial failed to demonstrate a significant clinical benefit of the NMDA‐receptor antagonist memantine in chronic PLP. The administration of a higher dosage is probably not tolerable.

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.

Reorganization in the ipsilateral motor cortex of patients with lower limb amputation

The aim of the present study was to assess reorganization in the motor cortex of patients with lower limb amputation. We studied seven patients with traumatic lower limb amputation, and six healthy controls, using transcranial magnetic stimulation mapping, with recordings from the quadriceps femoris muscle on both sides. Motor threshold, sum of amplitudes, area and the amplitude-weighted centre of gravity (COG) of the motor output map were assessed. We found a significant lateral displacement of the COG on the hemisphere contralateral to the healthy leg, whereas other parameters did not differ significantly between sides. This finding might be indicative of cortical reorganization in the hemisphere ipsilateral to the amputation. It is discussed with respect to an altered peripheral input to this hemisphere, and to transcallosal interactions from the deafferented hemisphere.

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.

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.

Role of Opioid Analgesics in the Treatment of Chronic Non-Cancer Pain

For more than 15 years opioids have been administered for chronic non-cancer pain. Refractory, chronic and extreme pain — even when associated with a noncancerous disorder — should in many cases be considered ‘malignant’ on the basis of its quality and intensity. Clinical studies demonstrate that patients with pain of non-cancer origin may benefit from opioid therapy, if other therapeutic measures are ineffective. However, opioid therapy can fail to be effective and well tolerated if the choice of opioid is inappropriate, if dosages are inadequate or because of prescribing restrictions in many countries. Therefore, the lack of success of opioid therapy is largely due to factors other than pain unresponsiveness.Issues still to be resolved regarding long term opioid therapy concern whether non-cancer pain is an appropriate indication for opioids, long term effectiveness, the potential for physical dependence, abuse and addiction, and such adverse events as constipation and neuropsychiatric toxicity. For patients with chronic non-cancer pain it is important not only to reduce pain with opioid therapy, but also to improve performance. There is evidence showing both impaired and improved psychomotor performance during opioid therapy.The role of opioids in non-cancer pain will therefore remain controversial while there is a lack of controlled studies investigating their use in the long term treatment of this condition.

2a NSAIDs and other non-opioids in chronic pain

Non-opioids are first-line drugs for long-term pain therapy. They are effective and have a low incidence of side-effects. There are differences between non-opioids, allowing for differential indications in order to improve efficacy as well as safety. While patients with low back pain and osteoarthritis are often treated well using pure analgesics, patients with rheumatoid arthritis, and in particular those with ankylosing spondylitis, require the most potent anti-inflammatory drugs. Patients with cancer pain of moderate-to-severe intensity also benefit from them, but this is limited by the progression of the disease and the ceiling effect of non-steroidal anti-inflammatory drugs (NSAIDs). Regular endoscopic investigation of the upper gastro-intestinal tract should be considered for the prevention of fatal side-effects in patients at risk. The choice of drugs for treatment must be based on outcome studies of high quality. According to the selection of studies presented, a few drugs can be ranked, those with highest safety first: ibuprofen, tenidap, fenbufen, aceclofenac, indomethacin, ketorolac, diclofenac, tenoxicam, piroxicam and ASA.