A Conditioning Sciatic Nerve Lesion Triggers a Pro-regenerative State in Primary Sensory Neurons Also of Dorsal Root Ganglia Non-associated With the Damaged Nerve

The study investigates how nerve damage in one area can trigger a healing response in nerve cells located in a different, undamaged area. Researchers found that damaging the sciatic nerve in rats led to increased production of proteins associated with nerve regeneration, not only in the area of damage but also in remote areas. The study suggests that this widespread regenerative response may involve a systemic reaction mediated by the signaling molecule IL-6. These results indicate that the pro-regenerative state of cervical DRG neurons illustrates a systemic reaction along the neuroaxis to unilateral sciatic nerve injury, and that this reaction can be mediated by IL-6 and JAK2/STAT3 signaling. Moreover, the results suggest a role for inflammatory mediators in activating the neuronal pro-regenerative state without direct retrograde axonal transport of signaling molecules from the injured nerve.

• 1
  A unilateral sciatic nerve injury leads to a bilateral increase in growth-associated protein-43 (GAP-43) and superior cervical ganglion-10 (SCG-10) mRNA and protein levels in both lumbar and cervical DRG neurons.
• 2
  Increased axonal regeneration capacity was observed in cervical DRG neurons after a prior conditioning sciatic nerve lesion, confirmed by both in vivo and in vitro assays.
• 3
  Intrathecal injection of IL-6 or a JAK2 inhibitor (AG490) revealed a role for the IL-6 signaling pathway in activating the pro-regenerative state in remote DRG neurons.