Interventional Modalities to Treat Complex Regional Pain Syndrome.

PURPOSE OF REVIEW: Complex regional pain syndrome (CRPS) is a debilitating pain condition that often requires a multidisciplinary approach including medication, physical therapy, occupational therapy, psychological therapy, and interventional procedures to restore the patient's quality of life. This article reviews the interventional treatments for pain resulting from CRPS. RECENT FINDINGS: Sympathetic nerve blocks (stellate ganglion and lumbar sympathetic) are the first-line interventional treatment options for patients with CRPS of the upper and lower extremities, respectively. Fluoroscopic techniques for lumbar sympathetic blocks have not significantly changed throughout the years. However, both novel fluoroscopic and ultrasound approaches to stellate ganglion blockade have arisen. In addition, novel neuromodulation therapies to treat CRPS have been developed to include new waveforms with dorsal column stimulation and entirely new nerve targets such as dorsal root ganglion stimulation. This paper will review the latest interventional treatment options available for the treatment of CRPS.

Modifications in fMRI Representation of Mental Rotation Following a 6 Week Graded Motor Imagery Training in Chronic CRPS Patients.

Complex regional pain syndrome (CRPS) is a neuropathic pain condition that is difficult to treat. For behavioral interventions, graded motor imagery (GMI) showed relevant effects, but underlying neural substrates in patient groups have not been investigated yet. A previous study investigating differences in the representation of a left/right hand judgment task demonstrated less recruitment of subcortical structures, such as the putamen, in CRPS patients than in healthy controls. In healthy volunteers, the putamen activity increased after a hand judgment task training. In order to test for longitudinal effects of GMI training, we investigated 20 CRPS patients in a wait-list crossover design with 3 evaluation time points. Patients underwent a 6 week GMI treatment and a 6 week waiting period in a randomized group assignment and treatment groups were evaluated by a blinded rater. When compared to healthy matched controls at baseline, CRPS patients showed less functional activation in areas processing visual input, left sensorimotor cortex, and right putamen. Only GMI treatment, but not the waiting period showed an effect on movement pain and hand judgment task performance. Regression analyses revealed positive associations of movement pain with left anterior insula activation at baseline. Right intraparietal sulcus activation change during GMI was associated with a gain in performance of the hand judgment task. The design used here is reliable for investigating the functional representation of the hand judgment task in an intervention study. PERSPECTIVE: Twenty chronic CRPS patients underwent a 6 week GMI intervention in a randomized wait-list crossover design. functional MRI was tested pre and post for the hand lateralization task which improved over GMI but not over WAITING. Performance gain was positively related to right parietal functional MRI activation.

Altered resting activity patterns and connectivity in individuals with complex regional pain syndrome.

Complex regional pain syndrome (CRPS) is a chronic neuropathic pain disorder that typically occurs in the limbs, usually the upper limb. CRPS usually develops from a peripheral event but its maintenance relies on changes within the central nervous system. While functional abnormalities in the thalamus and primary somatosensory cortex (S1) of the brain are some of the most consistently reported brain findings in CRPS, the mechanisms are yet to be explored in full, not least of all how these two regions interact and how they might relate to clinical deficits, such as the commonly reported poor tactile acuity in this condition. This study recruited 15 upper-limb CRPS subjects and 30 healthy controls and used functional magnetic resonance imaging (fMRI) to investigate infra-slow oscillations (ISOs) in critical pain regions of the brain in CRPS. As hypothesised, we found CRPS was associated with increases in resting signal intensity ISOs (0.03-0.06 Hz) in the thalamus contralateral to the painful limb in CRPS subjects. Interestingly, there was no such difference between groups in S1, however CRPS subjects displayed stronger thalamo-S1 functional connectivity than controls, and this was related to pain. As predicted, CRPS subjects displayed poor tactile acuity on the painful limb which, interestingly, was also related to thalamo-S1 functional connectivity strength. Our findings provide novel evidence of altered patterns of resting activity and connectivity in CRPS which may underlie altered thalamocortical loop dynamics and the constant perception of pain.

Neurogenic Thoracic Outlet Syndrome and other Forms of Cervical Brachial Syndrome Treated with Plasma Concentrate Enriched for Alpha 2 Macroglobulin.

BACKGROUND: Existing therapies for myofascial and neuralgic forms of cervicobrachial pain may have unsatisfactory outcomes. Alternative therapies may be considered, particularly for individuals who have failed to respond. Contemporary conceptualizations of chronic pain mechanisms include the contribution of inflammatory factors; therefore, locally targeted antiinflammatory administrations may play a role in treatment of cervicobrachial pain.Alpha 2 macroglobulin (A2M) is a plasma protein that acts as a molecular trap for inflammatory factors such as tumor necrosis factor. After plasma is enriched for A2M, it may be considered as a possible injectable agent to counteract inflammation that may occur with a cervicobrachial pain syndrome. OBJECTIVES: This retrospective review evaluates patient response to the use of plasma concentrate enriched for alpha 2 macroglobulin (A2M-PPP) in treatment of neurogenic thoracic outlet syndrome (TOS) and other forms of cervical brachial syndrome. STUDY DESIGN: Observational Study. SETTING: Outpatient interventional neurology practice. METHODS: There were 62 patients, including 46 women and 16 men ages 23-77 years. Twenty-three of these patients were diagnosed with complex regional pain syndrome (CRPS) or fibromyalgia, 18 with TOS, and 21 with musculotendinous pain (MTP). At baseline, 1 month, 3 months, and 6 months, patient status was evaluated with a Brief Pain Inventory (BPI) that included a composite pain score and a functional interference score. Patients were asked to estimate overall satisfaction with a Patient Global Impression of Change (PGIC) scale. Criterion for clinically significant improvement included >30% betterment in the BPI pain and functional interference subscales and a PGIC of > 5 at the 3-month mark. RESULTS: Three patients, one with CRPS and 2 with TOS, complained of several days of worsened pain or dysesthesias. No serious or permanent complications were encountered. For patients with TOS at the 3-month mark, 61% achieved clinical endpoints of success compared with 35% with CRPS/fibromyalgia and 24% for patients with MTP (P < 0.05, chi-square). By 6 months, 22% of individuals in the neuropathic TOS group had > 30% improvements in pain and functional interference scores compared with 13% of the individuals in the CRPS/fibromyalgia group and 18% in the MTP group. LIMITATIONS: This article does not differentiate the added benefit of A2M-PPP from hydrodissection alone. Additionally, this article does not evaluate the actual benefit of the A2M molecule apart from other factors present in the platelet-poor concentrate such as exosomes and cytokines. With the advent of pure engineered A2M, more focused studies will be possible. Also, an independent assay was not done, and therefore we cannot be precisely sure about the exact quantity of platelets, if any, which were contained in the platelet-poor concentration. CONCLUSIONS: Results suggest that A2M-PPP, when injected into muscle, tendon, and epineurium with live ultrasound guidance, appears to be relatively safe and free of postinjection inflammatory reactions that are often seen after platelet-poor plasma injection. A2M-PPP appears to be associated more frequently with good outcomes when injected into brachial plexus targets in patients with TOS compared with outcomes observed after injection of the plexus in patients with CRPS/fibromyalgia. KEY WORDS: Plasma concentrate enriched for alpha 2 macroglobulin, neurogenic thoracic outlet syndrome, cervical brachial syndrome.

[11C]-(R)-PK11195 positron emission tomography in patients with complex regional pain syndrome: A pilot study.

Complex regional pain syndrome (CRPS) is characterized by severe and chronic pain, but the pathophysiology of this disease are not clearly understood. The primary aim of our case-control study was to explore neuroinflammation in patients with CRPS using positron emission tomography (PET), with an 18-kDa translocator protein specific radioligand [C]-(R)-PK11195. [C]-(R)-PK11195 PET scans were acquired for 11 patients with CRPS (30-55 years) and 12 control subjects (30-52 years). Parametric image of distribution volume ratio (DVR) for each participant was generated by applying a relative equilibrium-based graphical analysis. The DVR of [C]-(R)-PK11195 in the caudate nucleus (t(21) = -3.209, P = 0.004), putamen (t(21) = -2.492, P = 0.022), nucleus accumbens (t(21) = -2.218, P = 0.040), and thalamus (t(21) = -2.395, P = 0.026) were significantly higher in CRPS patients than in healthy controls. Those of globus pallidus (t(21) = -2.045, P = 0.054) tended to be higher in CRPS patients than in healthy controls. In patients with CRPS, there was a positive correlation between the DVR of [C]-(R)-PK11195 in the caudate nucleus and the pain score, the visual analog scale (r = 0.661, P = 0.026, R = 0.408) and affective subscales of McGill Pain Questionnaire (r = 0.604, P = 0.049, R = 0.364). We demonstrated that neuroinflammation of CRPS patients in basal ganglia. Our results suggest that microglial pathology can be an important pathophysiology of CRPS. Association between the level of caudate nucleus and pain severity indicated that neuroinflammation in this region might play a key role. These results may be essential for developing effective medical treatments.

Musculoskeletal Ultrasonography in CRPS: Assessment of Muscles Before and After Motor Function Recovery with Dry Needling as the Sole Treatment.

BACKGROUND: Motor impairment is an important criterion in the Clinical Diagnostic Criteria (CDC) of Complex Regional Pain Syndrome type-1 (CRPS-1) as defined by International Association for Study of Pain (IASP). OBJECTIVE: To describe the changes in musculoskeletal ultrasonography (MSKUSG) in CRPS-1 before and after treatment with ultrasound-guided dry needling (USGDN) in retrospective data from 44 patients. STUDY DESIGN: Patients irrespective of age, gender, or cause of CRPS were included in this retrospective data analysis; the Budapest criteria for the diagnosis of CRPS were stringently adhered to. SETTING: The analysis was done at Ashirvad Institute for Pain Management and Research with the database of CRPS patients who were treated between December 2005 and December 2014. METHODS: The CDC, range of motion at upper extremity joints, dynamometry, Disability of arm, shoulder and hand score (DASH) and ultrasonography were documented on days one, 15, and 45. MSKUSG demonstrated loss of myoarchitecture and reduced bulk. RESULTS: All 44 patients received USGDN as the sole intervention with medications and physiotherapy. MSKUSG at 15 and 45 days after starting USGDN showed a return of normalcy to the myoarchitecture and muscle bulk increase that coincided with the disappearance of CDC and a progressive and predictable improvement of the DASH scores in all the 44 patients. LIMITATION: The analysis focuses on only 2 parameters: the musculoskeletal changes of the forearm flexors and extensors on ultrasound guidance and the efficacy of the dry needling treatment. It is not a comparative study with another accepted form of treatment or intervention. We have not looked into the age and gender predilection of the condition owing to the small sample size of the study. Analysis of long term maintenance of relief and rehabilitation of the disability were limited to one year. CONCLUSION: Myofascial pathology of co-contraction appears to cause CDC of CRPS and probable ischemic loss of myoarchitecture. Relief of co-contraction with USGDN allowed resolution of tenosynovitis causing the CDC and return of normal myoarchitecture.