Increased nerve growth factor signaling in sensory neurons of early diabetic rats is corrected by electroacupuncture

Purpose: Diabetic polyneuropathy (DPN) is early characterized by thermal hyperalgesia and increased neurotrophism, and lately evolves in irreversible neuropathic symptoms with dramatic reduction in nerve growth factor (NGF) support to sensory neurons. For this latter reason, NGF has been proposed as a therapeutic in DPN. Electroacupuncture (EA) is the western derivate of traditional Chinese acupuncture that is widely used in the clinical therapy of neuropathic pain. We recently demonstrated that EA was able to improve thermal hyperalgesia and to modulate NGF presence in the skin and spinal cord of early diabetic rats. In the present work we investigated the involvement of NGF signaling system in the early DPN and its possible modulation by EA. Methods: Diabetes was induced in rats by streptozotocin (STZ). One week after STZ, EA treatments were started and continued for three weeks. NGF and NGF receptors protein and mRNA, NGF signaling pathways and the presence of NGF-regulated transient receptor potential vanilloid receptor 1 (TRPV1) were analyzed in dorsal root ganglia (DRGs). NGF receptors expression and colocalization was analyzed in spinal cord and skin. Results: We found that STZ increased NGF and NGF receptors expression, activated c-Jun N-terminal kinase (JNK) and p38 kinase and increased TRPV1 in DRG; EA in diabetic rats decreased both NGF and NGF receptors, normalized JNK and p38 activation, decreased TRPV1 and activated the transcription factor Nf-?B. Expression of p75 neurotrophin receptor was increased in diabetic skin, while receptor tyrosine kinase A was increased in the spinal cord. EA in diabetic animals counteracted both these STZ-induced deregulations. Conclusions: The NGF could be primarily involved in DPN establishment and EA effects on DPN be mediated through the modulation of NGF signaling. Our findings point to EA, alone or in combination to NGF treatment, as a new possible therapeutic tool for DPN clinical care.