Regenerative Medicine for Neuropathic Pain: Physiology, Ultrasound and Therapies with a Focus on Alpha-2-Macroglobulin

Abstract

The currently available drugs to treat neuropathic pain do not provide adequate pain management. As such, other treatments including stem cells, platelet-rich plasma and plasma-derived molecules such as alpha-2 macroglobulin (A2M) are being explored because they show promising potential for neuropathic pain. The various mechanisms and immunomodulatory effects could be a desirable approach in targeting neuropathic pain. This review indicates that A2M can be highly efficacious due to its conformational change during activation and specificity of action on various cytokines. Its ability to reduce neuropathic pain can further the future of neuropathic intervention. However, there is a lack of robust clinical studies and thus further research is needed to verify and expand the understanding of its therapeutic effects.

Plain language summary

The currently available drugs to treat neuropathic pain do not provide adequate pain control. As such, other various regenerative treatments modalities are being explored because they show promising potential for neuropathic pain. The various mechanisms and immunity-focused effects could be a desirable approach in targeting neuropathic pain. This review indicates that alpha-2 macroglobulin, a specific plasma derived molecule, can be highly effective due to its shape change during activation and highly specific action on various proteins. Its ability to reduce neuropathic pain can further the future of neuropathic intervention. However, there is a lack of robust clinical studies and thus further research is needed to verify and expand the understanding of its therapeutic effects.

Keywords::

• alpha-2-macroglobulin
• neuropathic pain
• pain
• peripheral nerve injury
• regenerative intervention
• ultrasound

Author contributions

Concept and design: JC de Castro, D Wang, Acquisition, analysis, or interpretation of data: JC de Castro, D Wang, Critical revisions of the manuscript for important intellectual content: JC de Castro, GC Chien, D Wang, Administrative, technical, or material support: D Wang, Supervision: JC de Castro, GC Chien.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.