ReviewMast cells: Versatile gatekeepers of pain

- Mast cells are increasingly associated with pathophysiology of pain disorders.
- Mast cell-focused pre-clinical rodent models of pain can reveal relevant mechanisms.
- Mast cell-neuron synapses in the tissue modulate nociceptive signal cascades.
- Mast cell contributions to central and peripheral pain will inform new therapeutics.

Mast cells are important first responders in protective pain responses that provoke withdrawal from intense, noxious environmental stimuli, in part because of their sentinel location in tissue-environment interfaces. In chronic pain disorders, the proximity of mast cells to nerves potentiates critical molecular cross-talk between these two cell types that results in their synergistic contribution to the initiation and propagation of long-term changes in pain responses via intricate signal networks of neurotransmitters, cytokines and adhesion molecules. Both in rodent models of inflammatory pain and chronic pain disorders, as well as in increasing evidence from the clinic, it is abundantly clear that understanding the mast cell-mediated mechanisms underlying protective and maladaptive pain cascades will lead to improved understanding of mast cell biology as well as the development of novel, targeted therapies for the treatment and management of debilitating pain conditions.