Cerebral Dopamine Neurotrophic Factor (CDNF) Acts as a Trophic Factor Promoting Neuritogenesis in the Dorsal Root Ganglia (DRG) Neurons Through Activation of the PI3K Signaling Pathway.

The cerebral dopamine neurotrophic factor (CDNF) is a neurotrophic factor extensively studied in the central nervous system because of its neuroprotective effects; however, its role in the peripheral nervous system (PNS) remains less explored. In this study, we used primary dorsal root ganglia (DRG) explants to investigate the neuritogenic potential of exogenous CDNF, as well as its neuroprotective activity under trophic factor deprivation. Our findings demonstrate that CDNF-mediated neuroprotection remains unaffected by the addition of a Trk (tropomyosin receptor kinase) inhibitor or anti-nerve growth factor (NGF) antibody, indicating that CDNF's neurotrophic activity is independent of TrkA signaling.

PLCγ has a dual role in capsaicin-triggered neurogenic inflammation promoting mechanical hypersensitivity and edema in male mice.

Understanding the signaling mechanisms leading to neurogenic inflammation, a process found in chronic pain, psoriasis and migraine, is key for the development of more effective analgesics. A key player in the onset of this inflammation is transient receptor potential cation channel, subfamily V, member 1 (TRPV1), an ion channel abundant at the free terminals of nociceptors, which can be directly activated by capsaicin (CAP), acidic pH or noxious heat, and indirectly through phospholipase C-γ (PLCγ), which promotes cleavage of the inhibitory phosphatidylinositol-4,5-bisphosphate from the channel. In turn, PLCγ is activated via its phosphorylation by growth factor receptor tyrosine kinases, such as the high affinity nerve growth factor receptor, tropomyosin kinase A (TrkA).