C-fiber recovery cycle supernormality depends on ion concentration and ion channel permeability.

Following each action potential, C-fiber nociceptors undergo cyclical changes in excitability, including a period of superexcitability, before recovering their basal excitability state. The increase in superexcitability during this recovery cycle depends upon their immediate firing history of the axon, but also determines the instantaneous firing frequency that encodes pain intensity. To explore the mechanistic underpinnings of the recovery cycle phenomenon a biophysical model of a C-fiber has been developed.

Differential axonal conduction patterns of mechano-sensitive and mechano-insensitive nociceptors--a combined experimental and modelling study.

Cutaneous pain sensations are mediated largely by C-nociceptors consisting of both mechano-sensitive (CM) and mechano-insensitive (CMi) fibres that can be distinguished from one another according to their characteristic axonal properties. In healthy skin and relative to CMi fibres, CM fibres show a higher initial conduction velocity, less activity-dependent conduction velocity slowing, and less prominent post-spike supernormality. However, after sensitization with nerve growth factor, the electrical signature of CMi fibres changes towards a profile similar to that of CM fibres.

Modeling activity-dependent changes of axonal spike conduction in primary afferent C-nociceptors.

Action potential initiation and conduction along peripheral axons is a dynamic process that displays pronounced activity dependence. In patients with neuropathic pain, differences in the modulation of axonal conduction velocity by activity suggest that this property may provide insight into some of the pathomechanisms. To date, direct recordings of axonal membrane potential have been hampered by the small diameter of the fibers.

Long-lasting small-amplitude TRP-mediated dendritic depolarizations in CA1 pyramidal neurons are intrinsically stable and originate from distal tuft regions.

In several regions of the nervous system, neurons display bi- or multistable intrinsic properties. Such stable states may be subthreshold and long-lasting, and can appear as a sustained afterdepolarization. In hippocampal CA1 pyramidal neurons, small-amplitude (1 mV) long-lasting (seconds) afterdepolarizations have been reported and are thought to depend on calcium-activated nonselective (CAN) currents recently identified as transient receptor potential (TRP) channels.

Low-frequency summation of synaptically activated transient receptor potential channel-mediated depolarizations.

Neurons sum their input by spatial and temporal integration. Temporally, presynaptic firing rates are converted to dendritic membrane depolarizations by postsynaptic receptors and ion channels. In several regions of the brain, including higher association areas, the majority of firing rates are low.