Microglial signalling mechanisms: Cathepsin S and Fractalkine

Exp Neurol. 2012 Apr;234(2):283-92. doi: 10.1016/j.expneurol.2011.09.012. Epub 2011 Sep 17.


A recent major conceptual advance has been the recognition of the importance of immune system-neuron interactions in the modulation of spinal pain processing. In particular, pro-inflammatory mediators secreted by immune competent cells such as microglia modulate nociceptive function in the injured CNS and following peripheral nerve damage. Chemokines play a pivotal role in mediating neuronal-microglial communication which leads to increased nociception. Here we examine the evidence that one such microglial mediator, the lysosomal cysteine protease Cathepsin S (CatS), is critical for the maintenance of neuropathic pain via cleavage of the transmembrane chemokine Fractalkine (FKN). Both CatS and FKN mediate critical physiological functions necessary for immune regulation. As key mediators of homeostatic functions it is not surprising that imbalance in these immune processes has been implicated in autoimmune disorders including Multiple Sclerosis and Rheumatoid Arthritis, both of which are associated with chronic pain. Thus, impairment of the CatS/FKN signalling pair constitutes a novel therapeutic approach for the treatment of chronic pain.

Publication types

  • Review

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / physiopathology
  • Cathepsins / metabolism*
  • Chemokine CX3CL1 / metabolism*
  • Chronic Pain / metabolism*
  • Chronic Pain / physiopathology
  • Humans
  • Microglia / metabolism*
  • Neuralgia / metabolism
  • Neuralgia / physiopathology
  • Nociception / physiology*
  • Signal Transduction / physiology*


  • Chemokine CX3CL1
  • Cathepsins
  • cathepsin S