22 distal extremities,6 it also commonly presents with a non-length-dependent character.15 Non-length dependent SFN is likely to be associated with immune-mediated conditions and it presents more often in women at younger age.44 Somatic system The somatic nervous system is responsible for voluntary muscle control and sensory function. Sensory function, is broadly divided into special senses and general senses. Special senses include olfaction, vision, hearing, balance, and taste. General senses are divided into exteroceptors, (present in skin: nociception (pain, temperature, touch, pressure)), interoceptors (present in viscera: mechanical and chemical stimuli) and proprioceptors (present in muscles, joints and tendons: awareness of posture and movement).45 SFN mainly results in symptoms caused by damage of the nociceptive system. As a result, patients complain about pain, burning, tingling, prickling, shooting pain or numbness. Due to difference in conduction velocity, Aδ-fibers are responsible for the sharp, pricking or first pain response and C-fibers for the burning or second pain response, see Figure 1B.33 Aδ-fibers which respond to heat, are divided into type I and II A mechano-heat (AMH) units. AMH type I nerve fibers have a high response threshold (>53 0C), and their discharge rate increase during a prolonged stimulus. Typically type I AMH fibers show a higher sensitivity for mechanical stimuli compared to AMH type II fibers. AMH type II fibers have a short-latency adapting response, they have a lower threshold for heat stimuli (43-47 0C) and exhibit slower conduction velocities.46 As consequence, AMH type I fibers are responsible for first pain sensation of mechanical stimuli and AMH type II fibers are involved in first pain sensation of heat pain stimuli.33,38 C-fibers can be polymodal; responsive for noxious, thermal and mechanical stimuli. In addition, they can be responsive for a specific stimulus, but also for multiple stimuli or for non-specific stimuli.47 Table 2 shows an overview of functions from specific small fiber types. Also, specific temperature thresholds are shown, which are used for Quantitative Sensory Testing (QST) measurements. Figure 1 A) Overview of nerve fiber sizes, conduction velocities and other characteristics. Aα and Aβ fibers are large and myelinated nerve fibers, Aδ nerve fibers are small myelinated nerve fibers and C-fibers are small unmyelinated nerve fibers. B) Corresponding pain response. Large nerve fibers show a fast response with high amplitude. The smaller the nerve fiber, the lower the amplitude and the slower conduction velocities. 2 24 2
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