Functional anatomy of cutaneous capsaicin-sensitive afferent nerves (dedikált példány) [antikvár]

¦HsilKHH Introduction The skin is a major sensory organ, which contains different receptors of afferent nerve fibres. Sensory ganglion neurons giving rise to afferent nerve fibres serving cutaneous sensory receptors can be classified by their receptive properties, cell body size, peptide, enzyme or neurofilament content and specific membrane receptors. A significant population of primary afferent fibres is characterized by its exquisite sensitivity to capsaicin and related compounds. Capsaicin, the pungent agent of red pepper, is generally recognized as a potent sensory neurotoxin which affects a well-defined population of small diameter priipary afferent neurons. These chemosensitive, i.e. capsaicin-sensitive neurons express VRl-type vanilloid/capsaicin receptor molecules in their cell membrane and they can be selectively stimulated and/or functionally inactivated by capsaicin. In the skin, C-fibre polymodal nociceptors are the primary targets of the effects of capsaicin. These fibres transmit nociceptive impulses towards the central nervous system and, by the release of different neuropeptides from their stimulated peripheral nerve endings, they are responsible for local effector responses in the skin. These involve axon reflex vasodilatation and increased plasma protein extravasation (neurogenic inflammation), mast cell degranulation and recruitment of inflammatory cells. Capsaicin given systemically to newborn rats causes specific impairments in sensory function due to a selective irreversible degeneration of small-sized sensory ganglion neurons resulting in a loss of unmyelinated C- and thinly myelinated A5-fibres of 70 and 10 per cent, respectively. Systemic capsaicin treatment results in a selective impairment of capsaicin-sensitive afferent neurons all over the body. Topical application of capsaicin to a peripheral nerve proved to be an adequate and reliable technique to produce a selective and permanent chemical lesion of chemosensitive afferent nerves supplying a particular organ or some part of it. Functional impairments following application of capsaicin onto a peripheral nerve include a complete abolition of the neurogenic inflammatory response and marked thermal and chemical analgesia in the skin area served by the treated nerve. These functional alterations are accompanied by significant changes in the chemistry of primary sensory neurons. Histochemical and biochemical investigations have revealed a marked depletion of peptides and other sensory neuron-specific macromolecules from the central terminals and the perikarya of small sensory ganglion cells. Although these findings indicated profound changes in the chemistry of primary sensory neurons, they have yielded little information on the nature of these changes. In particular, it is unclear whether these changes are associated with an irreversible structural impairment of sensory neurons, or they merely reflect a depletion of peptides and proteins from these neurons.