Prokineticin1 and prokineticin2 belong to a new family of chemokines identified in
several species including mammals and characterized by the presence of five disulfide
These proteins signal through two G-coupled receptors (prokineticin-receptor1 and prokineticin-
receptor2) widely expressed in all tissues and involved in a large spectrum of biological
activities, including angiogenesis, hematopoiesis, immune processes, inflammation and
nociceptive transmission. Prokineticin2 is overexpressed in inflamed tissues and has a crucial
role in neutrophil dependent inflammation and hypernociception.
Following tissue inflammation, peripheral nerve injury, cancer, bone metastasis the expression
of prokineticin2 and of the prokineticin-receptor2 is increased also within dorsal root
ganglia and spinal cord. Prokineticin receptors, highly expressed in nociceptor endings and
dorsal root ganglia, exert a tonic activation of TRPV1 and TRPA1 contributing to peripheral
sensitization. Prokineticin2-induces activation of the prokineticin receptors in the spinal dorsal
horn and in activated astrocytes contributes to central sensitization and maintains chronic
and neuropathic pain.
Prokineticin2, acting on prokineticin receptors on monocytes, macrophages and dendritic
cells, induces chemotaxis and release of inflammatory and pronociceptive cytokines. Hence,
the prokineticin system represents a novel therapeutic target in chronic pain conditions.
Evaluation of the mechanism of action of prokineticin2 and the potential effectiveness of its
inhibition is discussed.