Met-enkephalin is preferentially transported into the peripheral processesof primary afferent fibres in both control and HSV1-driven proenkephalin aoverexpressing rats

The demonstration of preproenkephalin A gene expression in rat dorsal root ganglia has raised the question of the physiological role of mel-enkephalin -containing primary afferent fibres. Recently, we showed that systemic infe ction 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 furth er investigated the synthesis, transport and release of met-enkephalin-like material in the central and/or peripheral processes of primary afferent fi bres in HSVLatEnk1-infected and control rats. In controls, dorsal root gang lia 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 proxi mal side of ligatured sciatic nerve, but not in ligatured L4-L5 dorsal root s. In HSVLatEnk1-infected rats with numerous somas and fibres stained for m et-enkephalin-like material in dorsal root ganglia, met-enkephalin immunore active material largely accumulated at the proximal side of the ligatured s ciatic nerve and few positively stained fibres were also observed in ligatu red dorsal roots. Electrical stimulation of L4-L5 dorsal roots attached to a dorsal slice of the lumbar enlargement produced an overflow of met-enkeph alin-like material which was similar to 70% higher in HSVLatEnk1-infected r ats compared to controls. Al the periphery, subcutaneous microdialysis show ed higher basal levels of met-enkephalin-like material in the interstitial fluid of hindpaw plantar area in HSVLatEnk1-infected rats, and electrical s timulation of the ipsilateral sciatic nerve resulted in an approximately th ree fold-higher overflow of this material than in control rats. These data demonstrated that met-enkephalin synthesised in dorsal root gang lion of both control and preproenkephalin A overexpressing rats is preferen tially transported into the peripheral processes of primary efferent fibres where the peptide reaches a releasable compartment, thus providing a neuro nal source of peripheral met-enkephalin. (C) 2001 IBRO. Published by Elsevi er Science Ltd. All rights reserved.