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ERK and STAT3 phosphorylation in sensory neurons during capsaicin-induced impairment and nerve growth factor
J Donnerer1, I Liebmann, R Schicho
1Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria. josef.donnerer@meduni-graz.at
Abstract:
Distinct signal transduction pathways have been shown to regulate injury responses and regeneration in peripheral nerves. In the present investigation, the time courses of the induction of phospho-MAPK/ERK1/2 and of phospho-STAT3 were investigated in the dorsal root ganglia (DRG) and in the sciatic nerve of rats following a systemic capsaicin treatment without or with concomitant intraplantar NGF injections. Western blots were probed with polyclonal antibodies that specifically detect phosphorylated ERK 1/2 and STAT3. Phosphorylation of ERK clearly peaked in the sciatic nerve and in the lumbar DRGs at 6 and 10 h after the capsaicin treatment. In the following 8 days phospho-ERK decreased to very low levels and was found recovered to basal values at the time point 16 days. An additional intraplantar nerve growth factor (NGF) injection at time points 20, 44 and 92 h after the capsaicin treatment, and collection of tissues 4 h later, markedly increased the level of phospho-ERK in the sciatic nerve as well as in the DRG, as compared to the samples taken from rats at the same time points with a capsaicin treatment only. Posphorylated STAT3, which was almost non-detectable in the control sciatic nerve, clearly peaked at 6 h after the capsaicin treatment and decreased again during the following days to almost undetectable levels. The intraplantar NGF injections slightly stimulated phosho-STAT3 in the sciatic nerve. A basal level of phosphorylated STAT3 was present in DRGs of control animals, it remained at a high level up to 6 h after the capsaicin treatment, then markedly decreased and recovered on day 8 and day 16. NGF increased STAT3 phosphorylation in DRG on day 1 and day 2 above the level observed in samples taken from rats at the same time points with a capsaicin treatment only. The present study demonstrates that a capsaicin impairment of small diameter primary sensory neurons followed by an NGF treatment evokes a characteristic pattern of ERK and STAT3 activation indicative of neuronal degeneration and regeneration.
Insights
Capsaicin treatment activates ERK and STAT3 pathways in rat nerves, indicating neuronal damage. Nerve growth factor (NGF) injections modulated these signals, suggesting a role in nerve regeneration.
Area of Science:
- Neuroscience
- Cellular Biology
- Signal Transduction
Background:
- Peripheral nerve injury triggers complex signaling pathways.
- ERK and STAT3 are key players in cellular responses to stress and growth factors.
Purpose of the Study:
- To investigate the temporal activation patterns of phospho-MAPK/ERK1/2 and phospho-STAT3 in rat dorsal root ganglia (DRG) and sciatic nerve following capsaicin treatment.
- To determine the effect of intraplantar nerve growth factor (NGF) injections on these signaling pathways after nerve injury.
Main Methods:
- Western blot analysis was used to detect phosphorylated ERK1/2 and STAT3 levels.
- Rats were subjected to systemic capsaicin treatment, with or without intraplantar NGF injections at specific time points.
- Tissues (DRG and sciatic nerve) were collected at various time points post-treatment for analysis.
Main Results:
- Capsaicin treatment induced a rapid and transient peak in phospho-ERK in both the sciatic nerve and DRG, followed by a decrease to basal levels.
- NGF injections significantly enhanced phospho-ERK levels in both tissues compared to capsaicin treatment alone.
- Phospho-STAT3 showed a distinct temporal pattern, peaking early after capsaicin treatment in the sciatic nerve and exhibiting a different profile in the DRG, with NGF modulating its levels.
Conclusions:
- Capsaicin-induced nerve injury triggers specific temporal activation of ERK and STAT3 signaling pathways.
- NGF treatment influences these pathways, suggesting a role in modulating neuronal degeneration and regeneration processes.
- The observed patterns of ERK and STAT3 activation provide insights into the molecular mechanisms underlying peripheral nerve injury response and repair.
