Role of Neurotrophins in Neuropathic Pain

Dario      Siniscalco; Catia      Giordano; Francesco      Rossi; Sabatino      Maione; Vito      de Novellis

Abstract

Neurotrophins (NTs) belong to a family of structurally and functionally related proteins, they are the subsets of neurotrophic factors. Neurotrophins are responsible for diverse actions in the developing peripheral and central nervous systems. They are important regulators of neuronal function, affecting neuronal survival and growth. They are able to regulate cell death and survival in development as well as in pathophysiologic states. NTs and their receptors are expressed in areas of the brain that undergo plasticity, indicating that they are able to modulate synaptic plasticity. Recently, neurotrophins have been shown to play significant roles in the development and transmission of neuropathic pain. Neuropathic pain is initiated by a primary lesion or dysfunction in the nervous system. It has a huge impact on the quality of life. It is debilitating and often has an associated degree of depression that contributes to decreasing human well being. Neuropathic pain ranks at the first place for sanitary costs. Neuropathic pain treatment is extremely difficult. Several molecular pathways are involved, making it a very complex disease. Excitatory or inhibitory pathways controlling neuropathic pain development show altered gene expression, caused by peripheral nerve injury. At present there are no valid treatments over time and neuropathic pain can be classified as an incurable disease. Nowadays, pain research is directing towards new molecular methods. By targeting neurotrophin molecules it may be possible to provide better pain control than currently available.

Keywords: Neurotrophins, BDNF, NGF, NT-3, NT-4, neuropathic pain, neurotrophin-4 (NT-4), neuronal functions, synaptic plasticity