Although the therapeutic potential of vein wrapping (VW) for recurrent compressive neuropathy has been widely reported, the mechanisms underlying this technique have not been characterized. M2 macrophages induced by interleukin-4 (IL-4) or interleukin-10 (IL-10) have an anti-inflammatory function and play an important role in peripheral nerve repair. To evaluate whether VW promotes M2 polarization, we divided chronic constriction injury (CCI) rats into untreated and VW (CCI + VW)-treated groups. Pain withdrawal thresholds in both groups were evaluated using von Frey filaments. Expression of the anti-inflammatory cytokines IL-4 and IL-10 in vein and nerve were quantified using real time polymerase chain reaction (RT-PCR), and expression of the anti-inflammatory M2 macrophage markers CD206 and arginase-1 (Arg1) after VW was assessed by RT-PCR and immunohistochemistry. To evaluate the effect of exogenous IL-4 or IL-10 on M2 macrophage-marker expression, CD11b-positive macrophages isolated from sciatic nerve were stimulated with recombinant IL-4 and IL-10. VW significantly increased the pain withdrawal threshold. IL-4 and IL-10 mRNA expression was higher in veins than in the sciatic nerve. VW significantly increased CD206 and Arg1 mRNA expression compared to the CCI group. The number of CD206- and Arg1-immunoreactive cells in nerve bundles was twofold higher in the CCI + VW than CCI group. Application of exogenous IL-4 doubled CD206 and Arg1 mRNA expression in CD11b-positive macrophages. These results show that vein-derived IL-4 potentiates the benefit of VW through the activation of M2 macrophages in the sciatic nerve. Our results may help to optimize current procedures for treating recurrent compressive neuropathy. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.
Keywords: M2 macrophages; interleukin-10; interleukin-4; neuropathic pain; vein wrapping.
© 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.