Prolonged ketamine infusion as a therapy for Complex Regional Pain Syndrome: Synergism with antagonism?
Pickering AE, McCabe CS.
School of Physiology & Pharmacology, Medical Sciences Building, University of Bristol, BS8 1TD.
Complex regional pain syndrome (CRPS) remains a troubling and often refractory pain condition for which the existing treatments are inadequate. The review by Niesters et al in this journal highlights the interesting findings of several recent studies of the NMDA receptor antagonist ketamine in the treatment of CRPS. These studies report a robust analgesic effect that outlasts the period of infusion by weeks. However set against these positive findings are the issues presented by Ketamine pharmacokinetics, side effects and also the observation that these analgesic benefits are not mirrored by improvements in function or affect. In this commentary we consider the wider perspective of the potential for developing and evaluating this sort of NMDA antagonist therapy for the long-term management of CRPS patients.
RS: The authors conclude by saying that ketamine has transitory analgesic benefit but that there are the challenges of the risk profile to tackle. To determine whether the benefits outweigh the risks, further high quality studies are required.
Deficient muscle activation in patients with Complex Regional Pain Syndrome and abnormal hand postures: An electromyographic evaluation.
Bank PJ, Peper CL, Marinus J, Beek PJ, van Hilten JJ.
Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands; Research Institute MOVE, Faculty of Human Movement Sciences, VU University Amsterdam, The Netherlands.
Motor abnormalities in Complex Regional Pain Syndrome (CRPS) are common and often characterized by a restricted active range of motion (AROM) and an increased resistance to passive movements, whereby the affected body part preferably adopts an abnormal posture. The objective of the present study was to obtain a better understanding of the factors that are associated with these abnormal postures and limitations of the AROM, and to investigate whether these motor impairments reflect dystonia.
We evaluated characteristics of surface EMG of the flexor carpi radialis and extensor carpi radialis muscles during active maintenance of various flexion-extension postures of the wrist of the affected and unaffected side in 15 chronic CRPS patients, and in 15 healthy controls.
Deviant joint postures in chronic CRPS – at least in those patients with some range of active movement – were not characterized by sustained muscle contractions, and limitations of the AROM were not attributable to excessive co-contraction. Rather, the agonistic muscle and its antagonist were activated in normal proportions, albeit over a limited range.
The AROM limitations and abnormal postures that are often observed in chronic CRPS patients are not associated with excessive muscle activity and hence do not exhibit the characteristics typical of dystonia.
We hypothesize that structural alterations in skeletal muscle tissue and pain-induced adaptations of motor function may contribute to the observed motor impairments. Our findings may have important clinical implications, since commonly prescribed treatments are aimed at reducing excessive muscle contraction.
RS: This study highlights the point that any treatment programme must be individualised to address the pain, other symptoms, deficits and limitations. A number of people with CRPS have movement disorders and the reasons can vary. Our job is to identify why the movement patterns have changed and address the problem accordingly with sensorimotor retraining.
Properties of human spinal interneurones: normal and dystonic control.
Marchand-Pauvert V, Iglesias C.
INSERM, U731, Paris, F-75651 France. email@example.com
The muscles that control wrist posture receive large inputs from reflexes driven by hand afferents. In several studies, we have investigated these reflexes by electrical stimulation of cutaneous (median nerve) and proprioceptive (ulnar nerve) afferents from the hand. Median stimulation produced short latency inhibition in all motor nuclei investigated, possibly through inhibitory propriospinal-like interneurones. Ulnar stimulation produced similar inhibition but only in wrist extensors. In the other motor nuclei, ulnar stimulation produced short latency excitation mediated by group I motoneuronal drive through both monosynaptic and non-monosynaptic pathways involving excitatory propriospinal-like interneurones. This was followed by late excitations mediated through spinal group II and trans-cortical group I pathways. These results show that these pathways are concerned with the integration of afferent inputs, proprioceptive and cutaneous, to control of wrist posture during hand movements. Patients with focal hand dystonia exhibit abnormal postures. To investigate whether these spinal pathways contribute to these conditions, the effects of ulnar stimulation on wrist muscle activity during voluntary tonic contraction were examined in patients who suffer writer’s cramp. Ulnar-induced inhibition of the wrist extensors was reduced on the dystonic side of patients compared with their normal side and controls. In patients who exhibited abnormal wrist posture, group II excitation of the wrist flexors was also modified on the dystonic side. Cutaneous stimuli, by contrast, increased wrist flexor EMG on both sides and only in patients who exhibited normal posture. We conclude that spinal interneurones have a significant role in integrating afferent inputs from the hand to control wrist posture during hand movements and that altered function in these spinal networks is associated with the complex pathophysiology of writer’s cramp.