Continuous brachial plexus blockade in combination with the NMDA receptor antagonist memantine prevents phantom pain in acute traumatic upper limb amputees.

BACKGROUND: Hyperexcitability of N-methyl-d-aspartate acid (NMDA) receptors may play an important role in the development of phantom limb pain (PLP). AIM OF THE STUDY: To investigate whether early treatment with the NMDA antagonist memantine attenuates phantom pain memory formation in traumatic amputees. METHODS: In a randomized, double-blind, controlled trial 19 patients with acute traumatic amputation of the upper extremity were investigated. All patients received postoperative analgesia by continuous brachial plexus anesthesia (ropivacaine 0.375% 5 ml/h) for at least 7 days. In addition, the patients received either memantine (20-30 mg daily, n=10) or placebo (n=9) for 4 weeks. RESULTS: Memantine treatment reduced the number of requested ropivacacine bolus injections during the first week and resulted in a significant decrease of PLP prevalence and intensity at 4 weeks and 6 months follow up, but not at 12 months follow up. CONCLUSIONS: We conclude that memantine can reduce intensity of phantom limb pain and might also prevent the development of PLP. However, despite the very early begin of treatment; no long-term effect on established PLP was evident.

Phantom limb pain: a report of two cases.

The efficacy of pre-emptive analgesia for phantom limb pain is still unclear. It is generally accepted that pre hyphen;amputation pain increases the incidence of phantom and stump pain, even if pre-emptive analgesia is performed before and during surgery and in the postoperative period. Two cases of traumatic upper limb amputations are described here with no pre-existing pain. Both received similar antinociceptive treatment by continuous block of the brachial plexus through infusion of ropivacaine 0.375% at 5 ml/h for 10 days. Treatment of case 1 was initiated immediately after surgery; however, this amputee developed intensive phantom limb pain which persisted at 6 months. Early use of the prosthesis after surgery was not possible for this patient. The intensity of phantom limb pain in case 2 decreased significantly after 6 months, even though brachial plexus blockade was not started until 5 weeks post-trauma. This patient used a functional prosthesis intensively beginning early after amputation. Serial magnetoencephalographic recordings were performed in both patients. Only case 2 showed significant changes of cortical reorganization. In case 1 markedly less cortical plasticity was found. A combination of relevant risk factors such as a painful neuroma, behavioural and cognitive coping strategies and the early functional use of prostheses are discussed as important mechanisms contributing to the development of phantom pain and cortical reorganization.

Cortical reorganization after digit-to-hand replantation.

Functional recovery after digit-to-hand replantation depends on the interaction of various factors. In addition to peripheral mechanisms, cortical and subcortical reorganization of digit representation may play a substantial role in the recovery process. However, cortical processes during the first months after replantation are not well understood. In this 25-year-old man who had traumatically lost digits II to V (DII-V) on his right hand, the authors used magnetoencephalographic source imaging to document the recovery of somatosensory cortical responses after tactile stimulation at four sites on the replanted digits. Successful replantation of DIV and DV was accomplished at the original position of DIII and DIV with mixed innervation. Cortical evoked fields could be recorded starting from the 10th week after digit-to-hand replantation. Initially, signals from all sites showed decreased amplitudes and prolonged latencies. In the subsequent six recordings obtained between the 12th and 55th week postreplantation, a continuous increase in amplitude but only a slight recovery of latencies were observed. Components of the recorded somatosensory evoked fields were localized in the primary somatosensory cortex (SI). The localizations of the replanted DIV showed a gradual lateral-inferior shift in the somatosensory cortex over time, indicating cortical reorganization caused by altered peripheral input. The authors infer from this shift that the original cortical area of the missing finger (DII) was taken over by the replanted finger. From these data the authors conclude that magnetic source imaging might be a reliable noninvasive method to evaluate surgical nerve repair and that cortical reorganization of SI is involved in the regeneration process following peripheral nerve injury.

The cortical somatotopic map and phantom phenomena in subjects with congenital limb atrophy and traumatic amputees with phantom limb pain.

The extent of the cortical somatotopic map and its relationship to phantom phenomena was tested in five subjects with congenital absence of an upper limb, four traumatic amputees with phantom limb pain and five healthy controls. Cortical maps of the first and fifth digit of the intact hand, the lower lip and the first toe (bilaterally) were obtained using neuroelectric source imaging. The subjects with congenital upper limb atrophy showed symmetric positions of the left and right side of the lower lip and the first toe, whereas the traumatic amputees with pain showed a significant shift (about 2.4 cm) of the cortical representation of the lower lip towards the hand region contralateral to the amputation side but no shift for the toe representation. In healthy controls, no significant hemispheric differences between the cortical representation of the digits, lower lip or first toe were found. Phantom phenomena were absent in the congenital but extensive in the traumatic amputees. These data confirm the assumption that congenital absence of a limb does not lead to cortical reorganization or phantom limbs whereas traumatic amputations that are accompanied by phantom limb pain show shifts of the cortical areas adjacent to the amputation zone towards the representation of the deafferented body part.

Effects of regional anesthesia on phantom limb pain are mirrored in changes in cortical reorganization.

The causes underlying phantom limb pain are still unknown. Recent studies on the consequences of nervous system damage in animals and humans reported substantial reorganization of primary somatosensory cortex subsequent to amputation, and one study showed that cortical reorganization is positively correlated with phantom limb pain. This paper examined the hypothesis of a functional relationship between cortical reorganization and phantom limb pain. Neuroelectric source imaging was used to determine changes in cortical reorganization in somatosensory cortex after anesthesia of an amputation stump produced by brachial plexus blockade in six phantom limb pain patients and four pain-free amputees. Three of six phantom limb subjects experienced a virtual elimination of current phantom pain attributable to anesthesia (mean change: 3.8 on an 11-point scale; Z = -1.83; p < 0.05) that was mirrored by a very rapid elimination of cortical reorganization in somatosensory cortex (change = 19.8 mm; t(2) = 5.60; p < 0.05). Cortical reorganization remained unchanged (mean change = 1.6 mm) in three phantom limb pain amputees whose pain was not reduced by brachial plexus blockade and in the phantom pain-free amputation controls. These findings suggest that cortical reorganization and phantom limb pain might have a causal relationship. Methods designed to alter cortical reorganization should be examined for their efficacy in the treatment of phantom limb pain.

[Sympathetic reflex dystrophy in circumscribed stenosis of the abdominal aorta. Case report and discussion of pathophysiologic principles]. / Sympathische Reflexdystrophie bei umschriebener Stenose der Aorta abdominalis. Kasuistik und Diskussion der pathophysiologischen Grundlagen.

Reflex sympathetic dystrophy (RSD) is a pain syndrome characterized by somatosensory and motor disturbances, as well as by autonomic and trophic changes. The term is used in a descriptive sense and does not imply specific mechanisms of pathogenesis. We report on a patient who fulfilled the clinical criteria of RSD and who also displayed increasing impairment of peripheral blood supply. Angiography revealed a circumscribed stenosis of the abdominal aorta adjacent to the bifurcation. Disturbances in peripheral circulation as a potential cause of RSD are discussed.