Conditioning injury to adult mammalian sensory neurons enhances their regen
eration potential. Here we show that leukemia inhibitory factor (LIF) is a
fundamental component of the conditioning response. Conditioning injury in
vivo significantly increases the intrinsic growth capacity of sensory neuro
ns in vitro from LIF+/+ mice. This conditioning effect is significantly blu
nted in sensory neurons from LIF-/- mice. Enhanced growth is rescued in vit
ro in LIF-/- mice by the addition of exogenous LIF, and the effect blocked
by human LIF-05, an LIF receptor antagonist. Furthermore, we demonstrate th
at LIF promotes elongating but not arborizing neurite outgrowth in vitro an
d is required for normal regeneration of injured adult sensory neurons in v
ivo. LIF is also functionally protective to peptidergic sensory neurons aft
er nerve damage in vivo. Our results indicate that the alteration in intrin
sic growth status of injured sensory neurons depends, at least in part, on
LIF.