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. Author manuscript; available in PMC: 2018 Feb 1.
Published in final edited form as: Brain Behav Immun. 2016 Nov 7;60:282–292. doi: 10.1016/j.bbi.2016.11.003

Figure 7. Neuropathic pain maintained via a positive feedback loop between MT1-MMP and MBP (a hypothesis diagram).

Figure 7

After nerve injury, MT1-MMP unencumbered by TIMP-2 releases the algesic MBP peptides (e.g., MBP69-86) from the intact MBP. The algesic MBP peptides enhance the expression of MT1-MMP and other MMPs and produce pain via the proposed mechanism [6]. Interference with this positive feedback loop, and the release of other pro-algesic substrates using the short-term and localized MT1-MMP function-blocking hAb-DX2400 therapy reduces allodynia. In addition, MT1-MMP activates latent MMP-2, involved in the maintenance of the perineurial barrier and axonal growth. Selective targeting of the MMP-2-activating function of MT1-MMP using mAb-9E8 adversely affects nerve repair and is not effective against allodynia. TIMP-2 is an endogenous MT1-MMP and MMP-2 inhibitor with an algesic action after nerve injury [16].