AFGF, BFGF AND NGF DIFFERENTIALLY REGULATE NEUROPEPTIDE EXPRESSION INDORSAL-ROOT GANGLIA AFTER AXOTOMY AND INDUCE AUTOTOMY

Using immunohistochemistry and in situ hybridization the in vivo effec ts of acidic and basic fibroblast growth factor (aFGF, bFGF), and of n erve growth factor (NGF) on the expression of galanin, neuropeptide Y (NPY) and substance P in axotomized dorsal root ganglia (DRGs) were ex amined. Self-mutilation (autotomy), a supposed pain-related behavior, was investigated after growth factor treatment. One microgram of aFGF, bFGF or NGF was applied directly to the transected sciatic nerve via a capsule. Zn normal rats 3.2%, 0% and 17.5% of the neuron profiles in the DRGs contained galanin-, NPY- and substance P-like immunoreactivi ty (LI), respectively. Sciatic nerve transection induced a distinct in crease in galanin- and NPY-LIs, but a downregulation of substance P-LI . Thus three days after axotomy 23.5%, 26.9% and 9.8% of the DRG neuro n profiles showed immunoreactivity for galanin-, NPY- and substance P- LI, respectively. Ln vivo administration of aFGF counteracted the axot omy-induced increase in galanin and NPY, whereas bFGF only suppressed NPY upregulation. NGF reversed the injury-induced decrease in substanc e P-LI, but had no significant effect on galanin- and NPY-LIs. These r esults were confirmed by monitoring the mRNA levels for these neuropep tides. Moreover, aFGF was found to induce autotomy in 60% of the rats 3 days after axotomy. NGF produced autotomy in about 30% of the rats. Taken together, the present results suggest (1) that aFGF, bFGF and NG F differentially regulate neuropeptide expression in vivo: (2) that FG Fs can inhibit neuropeptide upregulation of some peptides after nerve injury; and (3) that aFGF and NGF may induce pain-related behavior.