Neonatal capsaicin treatment results in prolonged mitochondrial damage and delayed cell death of B cells in the rat trigeminal ganglia.

摘要

Capsaicin acts on the vanilloid receptor subtype 1, a noxious heat-gated cation channel located on a major subgroup of nociceptive primary afferent neurons. Following the systemic capsaicin treatment of neonatal rats, the loss of B-type sensory neurons in trigeminal ganglion of adult rats with chemoanalgesia and abolition of neurogenic inflammation was investigated. Our quantitative morphometric analysis revealed that in the trigeminal ganglion of neonatal rats treated with 50 mg/kg s.c. capsaicin, the total number of neurons, morphology of B-type cells and cell-size histograms did not differ from that of the controls 1 or 5 days after treatment. These observations indicate that early cell death does not play a significant part in the loss of B-type cells, which in our sample was 39.4% on the 19th day. However under the electron microscope pronounced selective mitochondrial swelling with disorganized cristae was observed in B-type neurons at 1-20 weeks after capsaicin treatment. Daily treatment with nerve growth factor (NGF, 10x100 &mgr;g/kg s.c.), started 1 day after capsaicin injection, prevented the loss of B-type cells but did not counteract the development of long-lasting mitochondrial damage. After NGF treatment, partial restitution of chemonociception to capsaicin instillation into the eye occurred but capsaicin-induced inhibition of neurogenic plasma extravasation in the hindpaw evoked by topical application of mustard oil remained unaltered. We conclude, that capsaicin treatment in neonatal rats, as in the adults, destroys terminal parts of the sensory neurons supplied by vanilloid receptors and induces long-lasting mitochondrial swelling in the soma. We hypothesize that loss of NGF uptake results in delayed cell death of B-type neurons in neonates.