Ricerc@Sapienza

Neuropathic pain represents a huge medical need affecting millions of individuals. The therapeutic approach remains a problem, as patients do not respond to traditional analgesics and even the efficacy of treatment with antiepileptics or antidepressants is poor. For these reason novel therapeutic strategies are urgently needed.
In neuropathic pain induced by nerve injury, damaged cells recruit circulating leukocytes and activate inflammatory cells, which produce several molecules, including chemokines.
Prokineticin 2 (PROK2) is a new chemokine that activating two G-protein coupled receptors, PKR1 and PKR2, localized in central and in peripheral nervous system, participates in the onset and progression of neuropathic pain. In different animal models of neuropathy, both PROK2 and PKRs result strongly up-regulated in the sciatic nerve, DRG and spinal cord and treatment with the PKRs antagonist PC1 reverses neuropathic pain restoring the PROK2/PKRs levels.
The project aims to understand if the prokineticin system plays a role not only in development but also in maintenance of neuropathic pain and also if this system may have a role in the regeneration of the nerve, after injury. For these reasons, we will evaluate in peripheral, spinal and supraspinal level, at several time points post-injury, the expression and distribution of PROK2/ PKRs, pro- and anti-inflammatory cytokines, the molecular phenotypes of infiltrating macrophages and of the glial cells. Moreover, in order to find out the role of the single prokineticin receptor in neuropathic pain, injury of the sciatic nerve will be induced in PKR1- and PKR2-KO mice and the time course of pain behavior will be evaluated up to complete recovery. At different time points after injury, we will evaluate the expression and distribution of PROK2/PKRs in peripheral and central nervous system as well as the single PKR-induced intracellular pathway that could contribute to neurodegeneration and/or nerve regeneration processes.