Abstract: In the last years, axonal conductance of action potential trains became a novel subject of study, changing the view of axons, from a static cable-like compartment to a more complex and dynamic system (Debanne et al., 2011). Axonal computation, indeed, is canonically constituted by the action of voltage-gated ion channels, such as the classic Na+ and K+ channels, but recent studies demonstrated that it can be modulated by the action of other ion channel pumps, and metabolic factors (Byczkowicz et al., 2019; Zang and Marder, 2021). These non-canonical mechanisms have been studied mainly in the central nervous system (Byczkowicz et al., 2019; Kamiya, 2019), and little is known about axonal conductance modulation in peripheral nerve fibers. Interestingly, the peripheral projecting neurons possess a pseudounipolar conformation and exceptionally long axons, an anatomical characteristic that make propagation and tuning of the axonal action potential more easily adjustable. Notably, unmyelinated axons (i.e. C-fiber nociceptors) prevail in all peripheral fibers as the most affected by changes in conduction velocity, since relatively small alterations cause substantial delays in action potential incoming time (Zang and Marder, 2021). Peripheral C-fiber nociceptors, indeed, are defined by specific activity-dependent slowing properties, whereby repetitive firing of nerve fibers results in the progressive slowing of their conduction velocity and concomitant increase in response latency (Gee et al., 1996). Activity-dependent slowing is so preserved to be designated as a signature mark able to discriminate among different functional C-fiber subtypes (Werland et al., 2021).