• Sheldon Jordan, Jessica Iovine, Taylor Kuhn, and Hugh Gelabert.
• Department of Surgery, Division of Vascular Surgery, University of California, Los Angeles, Los Angeles, CA.
• Pain Physician. 2020 Mar 1; 23 (2): 229-233.

BackgroundExisting 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.ObjectivesThis 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 DesignObservational Study.SettingOutpatient interventional neurology practice.MethodsThere 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.ResultsThree 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.LimitationsThis 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.ConclusionsResults 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 WordsPlasma concentrate enriched for alpha 2 macroglobulin, neurogenic thoracic outlet syndrome, cervical brachial syndrome.

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