Matrix Metalloproteinases in Neuropathic Pain and Migraine: Friends, Enemies, and Therapeutic Targets

Matrix metalloproteinases (MMPs) constitute a family of zinc-dependent endopeptidases that mediate extracellular matrix turnover and associated processes, such as cell survival, growth, and differentiation. This paper discusses important functions of MMP in the normal and injured nervous system, focusing on the role played by these proteases in neurological pain syndromes, most prominently in neuropathic pain and migraine headaches. In the past decade, metalloproteinases emerged as key modulators of neuropathic pain, with MMP-9 acting as an initiator of the neuropathic cascade. Increased MMP activity was detected in migraine patients, independent of aura, in tight association with metabolic derangements. The therapeutic implications of MMP inhibition are considered in the context of neurogenic pain regulation.