Pain Future Perspectives
In recent decades, much research effort has been directed to unravelling the underlying mechanisms of CRPS, and improving strategies for its prevention and treatment, alongside the unification of diagnostic procedures. An important issue to be addressed is the identification of prognostic factors for disease development, which could lead to a more targeted approach and therewith improve the prognosis of patients with CRPS. Prospective cohort studies on the development of CRPS are necessary to gain a better understanding of prognostic factors related to disease onset and disease course.82
as a derivation of the Budapest diagnostic criteria83
The recently developed CRPS severity score (CSS) might be helpful
in improving the systematic follow up of patients; however, validation of this tool is ongoing. CRPS remains a clinical diagnosis, and the patient population is heterogeneous. Although it has been proposed that CRPS comprises different disease subtypes or stages of the disease, this has not led to further subcategorisation of the disease.8 A targeted approach based on the identification of CRPS subtypes and specific mechanisms prevailing in an individual patient is therefore still warranted.
The many available treatment options suggest that the optimal therapy for CRPS has not yet been identified. Given the heterogeneous nature of CRPS, an optimal therapy seems unlikely; therefore, a mechanism-directed approach to treatment of CRPS appears preferable. With regard to interventions targeting inflammation, comparative studies of established interventions (e.g. prednisolone and DMSO) and novel anti-inflammatory agents, such as intravenous administration of immunoglobulin,84
performed. Furthermore, alternative approaches, such as targeting the cholinergic anti-inflammatory pathway,85
whereby activating the
parasympathetic nervous system to inhibit inflammatory activity and autonomic dysregulation in CRPS, could be pursued. Promising
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For each of the interventions discussed in this article, long-term studies of sufficient sample size, with specific attention to patient selection, timing and dosage of therapies, are required to establish risks and benefits of each intervention for patients with CRPS. n
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interventions addressing sensory disturbances related to peripheral and central sensitisation, such as NMDA receptor antagonists86 the N-type calcium channel blocker ziconotide,87 targets for further research.
and are worthwhile
Therapy directed at the stimulation of adaptive cortical reorganisation involving brain-training programmes, such as mirror therapy76 motor imagery,77
merit implementation in daily practice. Continuing this line of thought, a strong point can be made for increasing patients’ awareness and knowledge regarding mechanisms underlying the development of chronic pain and CRPS.88
within the field of exercise and occupational therapy should be focused on the distinction between pain and time-contingent approaches. Positive initial results have been found for pain exposure physical therapy (PEPT), which is based on progressive-loading exercises and desensitisation beyond the patients’ pain limits.89 Cognitive behavioural aspects are taken into account, with the goal to motivate patients to use the affected limb in daily activity despite experiencing pain. Likewise, for patients with CRPS with pain-related fear, research is ongoing into the effects of graded exposure therapy (GEXP), comprising provision of information about CRPS, observational learning and ‘flooding’ of feared movements and activities.
Repetitive transcranial magnetic stimulation (rTMS), whereby the motor cortex is stimulated to treat neuropathic pain, has been shown to provide short-term pain relief in patients with CRPS-1.90
issues related to placebo response and ways to prolong its efficacy need to be addressed.
EUROPEAN NEUROLOGICAL REVIEW
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