Health & Medical Neurological Conditions

Small Fibre Neuropathy and Painful Channelopathy

Small Fibre Neuropathy and Painful Channelopathy

What are the Small Fibres?

Small fibres are small narrow diameter myelinated (Aδ) and unmyelinated (C) nerve fibres of the peripheral nervous system (figure 2). Somatosensory Aδ-fibres and C-fibres innervating skin pass through the dermis where they innervate cutaneous structures; both groups of fibres end as free nerve endings in the epidermis (the Aδ-fibres lose their myelin sheath as they cross the dermo-epidermal junction). Aδ-fibres are responsible for conveying cold input and nociceptive input. C-fibres convey innocuous warm sensations and possibly innocuous cold sensations, and noxious input from a variety of high threshold mechanical, thermal and chemical stimuli. Small fibres play an important role in the autonomic nervous system, because thin myelinated fibres contribute to preganglionic fibres and C-fibres contribute to postganglionic fibres, innervating structures such as sweat glands, blood vessels and the heart. Nerve growth factor (discovered in a series of groundbreaking experiments by the Nobel laureate Rita Levi-Montalcini) is a key target-derived factor for these neurones. Mutations in nerve growth factor or its high-affinity receptor NTRK1 result in degeneration of nociceptors and sympathetic neurones; this leads to hereditary sensory and autonomic neuropathy type 5 and 4 respectively. The severe disability caused by painless injuries illustrates the vital importance of the nociceptive system.

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Figure 2.

(A) Confocal image of a skin biopsy taken from the finger of a healthy subject illustrating different subtypes of sensory fibre: PGP 9.5 is used as an axonal marker (red) and myelin basic protein as a marker for myelin (green). There are numerous free nerve endings entering the epidermis (white arrows) and a single myelinated fibre is innervating a Meissner's corpuscle (yellow arrow). (B) Electron micrograph of the sural nerve. The blue arrow shows a large diameter myelinated fibre, the purple arrow marks a small diameter myelinated fibre and the red arrow marks a Remak bundle in which one non-myelinating Schwann cell associates with multiple unmyelinated C-fibres which are ensheathed in Schwann cell pockets.

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