Velocity recovery cycles of C fibres innervating human skin

Abstract

Velocity changes following single and double conditioning impulses were studied by microneurography in single human C fibres to provide information about axonal membrane properties. C units were identified as mechano‐responsive (n= 19) or mechano‐insensitive (12) nociceptors, cold‐sensitive (8) or sympathetic fibres (9), and excited by single, double and triple electrical stimuli to the skin at mean rates of 0.25–2 Hz. The interval between single or paired (20 ms apart) conditioning stimuli and test stimulus was then varied between 500 and 2 ms, and recovery curves of velocity change against inter‐spike interval constructed, allowing for changes in these variables with distance. All fibres exhibited an initial (4–24 ms) relative refractory phase, and a long‐lasting (>500 ms) ‘H2’ phase of reduced velocity, attributed to activation of Na+/K+‐ATPase. Mechano‐responsive nociceptors exhibited an intermediate phase of either supernormality or subnormality, depending on stimulation rate. Mechano‐insensitive nociceptors behaved similarly, but all were supernormal at 1 Hz. Sympathetic units exhibited only a long‐lasting supernormality, while cold fibres exhibited a briefer supernormal and a late subnormal phase (H1), similar to A fibres. A pre‐conditioning impulse doubled H2 and increased H1, but did not augment supernormality or the subnormality of similar time course. Like A fibre supernormality, these phenomena were explained by a passive cable model, so that they provide an estimate of membrane time constant. Nociceptor membrane time constants (median 110 ms, n= 17) were rather insensitive to membrane potential, indicating few active voltage‐dependent potassium channels, whereas sympathetic time constants were longer and reduced by activity‐dependent hyperpolarisation.

Propofol decreases the axonal excitability in rat primary sensory afferents

“…of nerve fibres at high frequencies generate an activity-dependent hyperpolarization intracellulary limited by differences in the resting membrane potential prior to activation (Bostock et al, 2003) or a differential effectiveness of the electrogenic sodium pump (Na+/K+-ATPase) (Rang and Ritchie, 1968). In our experiments, the stimulation frequency of 1 Hz was too low to generate activity-dependent hyperpolarization.…”

Modulation of Action Potential Trains in Rabbit Saphenous Nerve Unmyelinated Fibers

“…An afterpotential is corresponding to (Q Na - Q K )/C, where Q Na and Q K is the quantity of Na + and K + ions flowing into the axon, and C is the capacitance of the membrane. When Q Na = Q K , all afterpotentials and post-spike velocity changes are absent due to the ‘passive time constant' mechanism [9]. This may account for the lack of changes in the other three ISIs.…”

“…Changes in axonal AP propagation during repetitive stimulation depend on the aftereffects of the preceding APs, that is, that immediately after the conduction of one AP, the axon undergoes a series of changes in oscillatory excitability, and this has been termed the recovery cycle [8]. In addition, the sequence of changes in axonal excitability after AP firing has been analyzed in detail [5,9,10,11,12]. The recovery cycle can last for several hundreds of milliseconds, which gives rise to periods of enhanced and reduced axonal excitability.…”

Activity-dependent slowing of conduction velocity in uninjured L4 C fibers increases after an L5 spinal nerve injury in the rat

“…Strong evidence suggests that this supranormality is due to a depolarizing charge on the neural membrane which decays with a time constant associated with the membrane capacitance/resistance (Weidner et al, 2002;Bostock et al, 2003). The amount of supranormality has been shown to increase as activity-dependent slowing increases (Weidner et al, 2002).…”

“…Handwerker, personal communication) and in myelinated fibers in an animal model of neuropathic pain (Shin et al, 1997;Won et al, 1997). Unmyelinated afferents also can exhibit supranormal conduction in response to twin pulse stimuli of short (e.g., 50 ms) interstimulus intervals (Weidner et al, 2002;Bostock et al, 2003) where the conduction velocity of the second action potential is greater than that of the first. Whether supranormal conduction is altered after nerve injury is not known.…”