The role of neurotrophic factors in genesis and maintenance of mechanical hypernociception after brachial plexus avulsion in mice

Abstract

Neurotrophic factors (NTFs), namely nerve growth factor (NGF), glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), have recently emerged as a new exciting class of potential targets for the development of drugs to treat chronic pain. We have recently reported that brachial plexus avulsion (BPA) results in a marked and long-lasting mechanical hypernociception in rodents. Here we demonstrate that antibodies against NGF, NT-3, GDNF and BDNF were able to postpone the mechanical hypernociception in mice when dosed locally, systemically or intrathecally (i.t.) at the time of surgery. However, none of them were able to interfere with the mechanical hypernociception when administered intraventricularly (i.c.v.) at the moment of surgery or even i.p. on the 4th day after the injury. Interestingly, the anti-BDNF antibody was the only one that substantially reversed the mechanical hypernociceptive state when administered i.t. or i.c.v. on the 4th day after the BPA. We might suggest that NTFs, notably BDNF, are involved in the mechanisms underlying neuropathic pain-like behavior following BPA. These pieces of evidence corroborate the notion that NTF blockers might represent a new and interesting option for the management of neuropathic pain.