Pain


Table 1: Diagnostic Criteria for Complex Regional Pain Syndrome (CRPS) Type 1


Budapest Clinical Diagnostic Criteria for CRPS Type 1 1. 2.


Continuing pain, which is disproportionate to any inciting event


Must report at least one symptom in three out of four of the following categories: • Sensory: reports of hyperesthesia and/or allodynia • Vasomotor: reports of temperature asymmetry and/or skin colour changes and/or skin colour asymmetry


• Sudomotor/oedema: reports of oedema and/or sweating changes and/or sweating asymmetry


• Motor/trophic: reports of decreased range of motion and/or motor dysfunction (weakness, tremor or dystonia) and/or trophic changes (hair, nail or skin)


3.


Must display at least one sign at time of evaluation in two or more of the following categories: • Sensory: evidence of hyperalgesia (to pinprick) and/or allodynia (to light touch and/or deep somatic pressure and/or joint movement)


• Vasomotor: evidence of temperature asymmetry and/or skin colour changes and/or asymmetry


• Sudomotor/oedema: evidence of oedema and/or sweating changes and/or sweating asymmetry


• Motor/trophic: evidence of decreased range of motion and/or motor dysfunction (weakness, tremor or dystonia) and/or trophic changes (hair, nail or skin)


4. There is no other diagnosis that better explains the signs and symptoms


spinal motor circuitry, resulting in movement disorders associated with CRPS, such as dystonia, tremor or myoclonia.34


Cortical Reorganisation


Pain and sensory disturbances in CRPS often spread from the location of the initial trauma to a larger area, sometimes even to another extremity, which might indicate plastic changes of the central nervous system owing to neurogenic inflammation.35


In patients with CRPS,


reorganisation of the primary somatosensory cortex (S1) has been observed, which correlated with the amount of pain and hyperalgesia experienced by the patients.36,37


Cerebral representation and motor


processing in the brain are also reported to be disturbed, possibly leading to movement disorders in CRPS-1 and distorted visualised representation of the affected limb.38–41


Psychological Factors


Psychological disturbances have often been proposed to be involved in complex conditions, such as chronic pain and CRPS. However, little evidence has emerged to support this hypothesis. No relation has been found between psychological dysfunction, disease-related fear or personality and the development of CRPS.42–44


One study reports that stressful life events are more common in patients with CRPS than in controls,45 could not confirm this finding.42,43,46,47


but other studies Once patients have developed


CRPS, pain-related fear and fear of re-injury are proposed to be risk factors for a poor prognosis relating to pain reduction and functional improvement.48,49


Treatment Options


Treatment of CRPS-1 is challenging, because of the variety of symptoms and the variable disease course exhibited by patients. A multimodal approach consisting of pharmacological treatment and physiotherapy, sometimes in combination with invasive therapy or psychological support, is required. An overview of systematic reviews


272 Calcium-regulating Drugs


The use of bisphosphonates has been proposed as a treatment option for CRPS. Although limited support for their ability to reduce pain (associated with bone loss) has been reported, additional research with regard to their dosage, frequency and duration of treatment is required.21,50,53,55,56,62,69,70


Vasodilatory Medication


For treatment of patients with CRPS and vasomotor disturbances, α-1 adrenergic blockers, phenoxybenzamine and terazosin, or calcium influx blockers, such as nifedipine, can be considered.4,55,71 No reduction in temperature asymmetry was found for NO-regulating medication (e.g. tadalafil or isosorbide dinitrate) in primary cold CRPS, although tadalafil is superior to placebo in reducing pain for this subgroup.72,73


Likewise, intravenous administration of ketanserine is reported to reduce pain in CRPS.50,74 Spasmolytics


Movement disorders in CRPS-1, such as dystonia, myoclonia and tremor, might benefit from treatment with baclofen or benzodiazepines.4,50,63


to be beneficial for CRPS-related movement disorders over a longer period of time.34


EUROPEAN NEUROLOGICAL REVIEW Treatment with anti-cholinergics has not shown


and guidelines providing an evidence-based approach to treatment of CRPS is presented in Tables 2 and 3.50–60


Pharmacological Treatment Analgesics


Pain medication according to the WHO analgesic ladder has been suggested in therapeutic guidelines, although evidence supporting the efficacy of paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDS) is limited. Tramadol has been shown to be effective in neuropathic pain disorders, therefore it can be considered for severe pain accompanying CRPS, although evidence for its effects in CRPS is lacking.4,50,51,55,61–63


Treating CRPS with strong opioids should only be considered as crisis management for a limited period of time.51,55 has proven efficacy in CRPS-1;50,51,55,62,64


Furthermore, gabapentin however, amitryptiline and


carbamazepine or newer tricyclic antidepressants (TCAs), such as duloxetine or venlafaxine, can also be considered, because of their shown effectiveness in other neuropathic pain disorders.50,55,62


Intravenous administration of the NMDA receptor antagonist ketamine can be considered; however the full scope of its therapeutical potential (including a risk–benefit assessment) has not yet been established.50,60,65,66


Lidocaine patches have been proposed for treatment of localised sensory deficits, such as allodynia in CRPS.67 Anti-inflammatory Therapy


The free radical scavenger dimethyl sulfoxide (DMSO) has been shown to be effective in patients who have had CRPS-1 for less than a year.58 N-Acetylcysteine (NAC) shows comparable efficacy to DMSO, but proved superior to DMSO for primary cold CRPS in subgroup analyses.68


CRPS after wrist fractures.23,24


Vitamin C has established efficacy in the prevention of Furthermore, corticosteroids can provide


significant pain reduction in CRPS; however, there is no consensus on the dosage or duration of treatment.50,58,62,63


have so far only been evaluated in early-stage CRPS.51,55 Both types of intervention


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