Changing the levels of
neurotrophins in the spinal cord micro-environment after
nervous system injury has been proposed to recover normal function, such that behavioral response to peripheral stimuli does not lead to
chronic pain. We have investigated the effects of recombinant adeno-associated viral (rAAV)-mediated over-expression of
brain-derived neurotrophic factor (
BDNF) in the spinal cord on chronic
neuropathic pain after unilateral chronic constriction injury (CCI) of the sciatic nerve. The rAAV-
BDNF vector was injected into the dorsal horn at the thirteenth thoracic spinal cord vertebra (L(1) level) 1 week after CCI.
Allodynia and
hyperalgesia induced by CCI in the hindpaws were permanently reversed, beginning 1 week after vector injection, compared with a similar injection of a control rAAV-GFP vector (
green fluorescent protein) or saline. In situ hybridization for
BDNF demonstrated that both dorsal and ventral lumbar spinal neurons contained an intense signal for
BDNF mRNA, at 1 to 8 weeks after vector injection. There was no similar
BDNF mRNA over-expression associated with either
injections of saline or rAAV-GFP. These data suggest that chronic
neuropathic pain is sensitive to early spinal
BDNF levels after partial nerve injury and that rAAV-mediated gene transfer could potentially be used to reverse
chronic pain after
nervous system injuries in humans.