Hayashida K, Clayton B, Ma W, Eisenach J (2006) Brain-derived neurotrophic growth factor from p75-expressing sensory afferents drives spinal noradrenergic fiber sprouting following nerve injury in rats. Neuroscience 2006 Abstracts 248.19. Society for Neuroscience, Atlanta, GA.
Summary: We previously showed that peripheral nerve injury in mice results in sprouting of noradrenergic (NA) fibers in the spinal cord, possibly reflecting a substrate for increased efficacy of α2-adrenoceptor agonists such as clonidine. Here we tested whether spinal NA fiber sprouting also occurs in rats after peripheral nerve injury and examined the role of brain derived neurotrophic factor (BDNF) for such sprouting. Ligation of L5 and L6 spinal nerves unilaterally in rats resulted in mechanical hypersensitivity of the paw ipsilateral to injury and sprouting of NA fibers in the dorsal horn of the lumbar spinal cord. BDNF content increased in L4-L6 dorsal root ganglia (DRG) ipsilateral to injury and in lumbar spinal cord following nerve injury and intrathecal infusion of BDNF antiserum prevented spinal NA sprouting. Pro-BDNF immunoreactivity increased in L4-L6 DRG neurons ipsilateral to injury, especially in large-size neurons, and was highly co-localized with the low affinity neurotrophin receptor, p75NTR. Intrathecal injection of anti-p75NTR linked to saporin destroyed p75NTR expressing afferents and reversed NA sprouting after nerve injury. Manipulations which blocked NA sprouting (BDNF antiserum, anti-p-75NTR saporin) also prevented the increased analgesic efficacy of intrathecal clonidine observed after nerve injury. These results suggest that increased BDNF synthesis and release from p75NTR expressing injured and uninjured sensory afferents drives spinal NA sprouting following nerve injury and this sprouting increase the capacity for analgesia from drugs which utilize the NA pathway.
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