The Cathepsin S/Fractalkine Pair: New Players in Spinal Cord Neuropathic Pain Mechanisms

  • Anna K. Clark
  • Marzia Malcangio


A recent major conceptual advance has been the recognition of the importance of immune system-neuronal interactions in the modulation of brain function. One example of which is spinal pain processing in neuropathic states. Mounting evidence supports the hypothesis that pro-inflammatory mediators secreted by microglia modulate nociceptive function in the injured CNS and following peripheral nerve damage. Here we examine the evidence that one such mediator, the lysosomal cysteine protease cathepsin S (CatS), is critical for the maintenance of neuropathic pain and spinal microglia activation in neuropathic pain states. CatS exerts its pro-nociceptive effects via cleavage of the transmembrane chemokine fractalkine (FKN). Under conditions of increased nociception, microglial CatS is responsible for the liberation of neuronal FKN which stimulates p38 MAPK phosphorylation in microglia thereby activating neurons via the release of pro-nociceptive mediators, thus establishing a new role for the CatS/FKN pair in the maintenance of neuropathic hypersensitivity and suggest that CatS inhibition constitutes a novel therapeutic approach for the treatment of chronic pain.


Neuropathic Pain Major Histocompatibility Complex Class Dorsal Horn Mechanical Allodynia Peripheral Nerve Injury 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



cathepsin S




antigen presenting cells


dendritic cells


major histocompatibility complex


invariant chain


class II-associated Ii peptide


human leukocyte antigen DM


morpholinurea-leucine-homophenylalanine-vinyl sulfone-phenyl


partial sciatic nerve ligation


chronic constriction injury


spinal nerve ligation


a disintegrin and metalloprotease domain


tumour necrosis factor-α converting enzyme


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Wolfson Centre for Age Related DiseasesKing’s College LondonSE1 1ULUK

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