The effect of intrathecal methylprednisolone on features of central sensitisation in patients with chronic complex regional pain syndrome (CRPS) type one

INTERVENTION: In all patients a lumbar puncture will be performed. After a lumbar puncture 5 ml of fluid is removed for cytologic and biochemical tests. An additional 5 ml of fluid will be removed for the measurement of the level of cytokines. Then 60 mg of Depo‐medrol® (methylprednisolone acetate) or placebo is injected. For patients whose pain is located in an arm the table will be tilted into the head‐down position immediately after the intrathecal injection to allow the injected material to spread to the upper thoracic canal. Patients with symptoms in the lower extremities are kept in a horizontal position. Outcomes will be assessed six weeks after the intervention. CONDITION: Chronic complex regional pain syndrome type 1 (CRPS I) ; Signs and Symptoms ; Complex regional pain syndrome PRIMARY OUTCOME: The severity of spontaneous pain is evaluated through a 10 cm visual analogue scale (0 cm represents no pain, 10 cm represents the worst imaginable pain). This will be filled in at home in a diary. Primary outcome is pain relief at six weeks. INCLUSION CRITERIA: Patients will be male or female, outpatients aged 18 to 75 years, with a clinical diagnosis of CRPS who are referred to the Leiden University Medical Centre (LUMC): 1. At onset patients must fulfill the criteria for CRPS I. These criteria include: 1.1. The combination of continuing pain 1.2. Allodynia or hyperalgesia 1.3. Rendering the pain disproportionate to any inciting event 1.4. Evidence at some time of oedema 1.5. Changes in skin blood flow 1.6. Abnormal sudomotor activity in the region of the pain 1.7. Absence of a condition which would otherwise account for the degree of pain and dysfunction 2. When entering the study patients must suffer from symptoms and signs indicative of central sensitisation (continuing pain, hyperalgesia and/or allodynia) 3. Patients must have symptoms for more than six months and shorter than six years 4. Use of pain medication must have been stable in the previous four weeks 5. Patients must be wi SECONDARY OUTCOME: 1. Sensory assessments:; 1.1. The nature of the pain is assessed by means of the neuropathic pain scale developed by Galer which consists of several visual analogue scales for different kinds of pain. Also a McGill Pain Questionnaire will be administered; 1.2. Hyper‐ and hypo‐esthesia and allodynia will be tested using Von Frey hairs; 1.3. Pain and temperature perception thresholds (Temperature Sensory Assessment using the Medoc TSA II Neurosensory Analyser). A thermode will be placed on the volar side of the wrist or dorsal side of the foot; 1.4. Somatosensory evoked potentials; 2. Autonomic assessments:; 2.1. Skin temperature of affected and contralateral extremity and midsternal; 2.2. The difference in volume between the affected and contralateral extremity is assessed by a volumeter as a measure for edema. This instrument measures the amount of water that is displaced by the immersed body part; 2.3. Pulse transit time (the time the pulse wave takes to travel from heart to finger) as a measure of peripheral vessel resistance; 3. Motor assessments:; 3.1. Patients will be evaluated for the presence and severity dystonia, myoclonus and tremor (none, intermittent, continuous); 3.2. Range of motion will be assessed using a universal goniometer; 3.3. In those patients in which this can be evaluated, movement velocity of repetitive fingertaps will be objectively quantified; 3.4. In those patients in which this can be evaluated, proprioceptive reflexes will be assessed using a wrist pertubator; 4. Disability:; 4.1. Patients will be asked to mark the change in function of the affected hand or foot on a scale from one to seven (one = maximal worse, four = no change, seven = maximal better); 4.2. Radboud skills questionnaire, walking stairs questionnaire and questionnaire rising and sitting down will be administered; 4.3. Participation and global health will be assessed using the Short Form (SF‐36)questionnaire, EuroQol 5D questionnaire, Inventarisatielijst Sociale Betrekkingen (ISB) and Impact on Participation and Autonomy (IPA); 5. (Serious) adverse events