Artemin has potent neurotrophic actions on injured C-fibres

• Published in: Journal of the peripheral nervous system 2006-12, Vol.11 (4), p.330-345
• Main Authors: Bennett, David L. H., Boucher, Timothy J., Michael, Gregory J., Popat, Reena J., Malcangio, Marzia, Averill, Sharon A., Poulsen, Kris T., Priestley, John V., Shelton, David L., McMahon, Stephen B.
• Format: Article
• Language: English
• Subjects: Animals; artemin; Axotomy; C-fibres; Cells, Cultured; Ganglia, Spinal - drug effects; Ganglia, Spinal - injuries; GFRα3; Glial Cell Line-Derived Neurotrophic Factor Receptors - metabolism; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; In Situ Hybridization; Mice; Nerve Regeneration - drug effects; Nerve Tissue Proteins - pharmacology; Neural Conduction - drug effects; Neurons, Afferent - drug effects; Neurons, Afferent - pathology; Neuroprotective Agents - pharmacology; pain; Rats; Recombinant Proteins - pharmacology; RET; Substance P - drug effects; Substance P - metabolism
• ISSN: 1085-9489; 1529-8027
• DOI: 10.1111/j.1529-8027.2006.00106.x

In this study, we have investigated the effects of artemin (ARTN), one of the glial cell line‐derived neurotrophic factor (GDNF) family of neurotrophic factors, on C‐fibres following nerve injury in the adult rat. GDNF family receptor alpha (GFRα) 3, the ligand binding domain of the ARTN receptor, is expressed in 34% of dorsal root ganglion (DRG) cells, predominantly in the peptidergic population of C‐fibres and in a proportion of the isolectin B4 (IB4)‐binding population. Interestingly, only 30% of GFRα3‐expressing DRG cells co‐expressed RET (the signal transducing domain). In agreement with previous studies, treatment with ARTN prevented many of the nerve injury‐induced changes in the histochemistry of both the peptidergic and the IB4‐binding populations of small, but not large, diameter DRG cells. In addition, ARTN treatment maintained C‐fibre conduction velocity, and C‐fibre evoked substance P release within the dorsal horn following nerve injury. ARTN was also protective following capsaicin treatment, which produces selective C‐fibre injury. Given the potent neurotrophic actions of ARTN on C‐fibres, it may therefore provide potential for the treatment of nerve injury, particularly in the maintenance of small fibre function.