Met-enkephalin is preferentially transported into the peripheral processes of primary afferent fibres in both control and HSV1-driven proenkephalin A overexpressing rats

The demonstration of preproenkephalin A gene expression in rat dorsal root ganglia has raised the question of the physiological role of met-enkephalin-containing primary afferent fibres. Recently, we showed that systemic infection with a recombinant Herpes simplex virus encoding preproenkephalin A (HSVLatEnk1) yielded a marked increase in the density of met-enkephalin-like material synthesising neurons in rat dorsal root ganglia. This study further investigated the synthesis, transport and release of met-enkephalin-like material in the central and/or peripheral processes of primary afferent fibres in HSVLatEnk1-infected and control rats. In controls, dorsal root ganglia neurons containing met-enkephalin-like material were scarce and only a few positively labelled processes were seen at the peripheral output of the dorsal root ganglia. Met-enkephalin-like material accumulated at the proximal side of ligatured sciatic nerve, but not in ligatured L4–L5 dorsal roots. In HSVLatEnk1-infected rats with numerous somas and fibres stained for met-enkephalin-like material in dorsal root ganglia, met-enkephalin immunoreactive material largely accumulated at the proximal side of the ligatured sciatic nerve and few positively stained fibres were also observed in ligatured dorsal roots. Electrical stimulation of L4–L5 dorsal roots attached to a dorsal slice of the lumbar enlargement produced an overflow of met-enkephalin-like material which was ∼70% higher in HSVLatEnk1-infected rats compared to controls. At the periphery, subcutaneous microdialysis showed higher basal levels of met-enkephalin-like material in the interstitial fluid of hindpaw plantar area in HSVLatEnk1-infected rats, and electrical stimulation of the ipsilateral sciatic nerve resulted in an approximately three-fold-higher overflow of this material than in control rats.