Objective: 

Investigation of the effect of endogenous opioids on the survival of primary sensory neurons following an axonal injury.

Methods: 

Local ethical committee approval was obtained prior to experiments. Primary sensory neurons were isolated from dorsal root ganglia of young adult mice and cultured in glass-bottom culture dishes. After 24 hours in culture, outgrown axons were precisely cut with a UV laser at 100 micrometer distance from the soma. The axotomies were performed under physiological conditions and in the presence of beta endorphin (5 uM), morphine (5uM) and / or other agents.

Results: 

Under control conditions, 24 hours after axotomy death rate was 70%, which was reduced to 46% by beta-endorphin (p<0.05). This effect was much more pronounced with selective mu agonist morphine (9%). Since beta endorphin has affinity also to delta opioid receptors (DORs) we tested the possibility that DORs may mediate a death signal in our experimental model. Indeed, when we blocked DOR activity with naltrindole (10 uM) or naltriben (10 uM) the death rate was reduced to 47 and 38% respectively (p<0.05). We have obtained many hints from other experiments that we performed to explain the mechanism underlying this dual role of opioid receptors on the survival of injured neurons, regarding opioid receptor trafficking between cytosole and cell membrane and receptor dimerization.

Conclusions: 

This study has shown that depending on the receptor subtype, endogenous opioids may be either a survival or a death factor for injured neurons. This novel finding may have implications in physiopathological processes as well as for pharmacological interventions.