Ionic mechanisms in peripheral pain

Abstract

Chronic pain constitutes an important and growing problem in society with large unmet needs with respect to treatment and clear implications for quality of life. Computational modeling is used to complement experimental studies to elucidate mechanisms involved in pain states. Models representing the peripheral nerve ending often address questions related to sensitization or reduction in pain detection threshold. In models of the axon or the cell body of the unmyelinated C-fiber, a large body of work concerns the role of particular sodium channels and mutations of these. Furthermore, in central structures: spinal cord or higher structures, sensitization often refers not only to enhanced synaptic efficacy but also to elevated intrinsic neuronal excitability. One of the recent developments in computational neuroscience is the emergence of computational neuropharmacology. In this area, computational modeling is used to study mechanisms of pathology with the objective of finding the means of restoring healthy function. This research has received increased attention from the pharmaceutical industry as ion channels have gained increased interest as drug targets. Computational modeling has several advantages, notably the ability to provide mechanistic links between molecular and cellular levels on the one hand and functions at the systems level on the other hand. These characteristics make computational modeling an additional tool to be used in the process of selecting pharmaceutical targets. Furthermore, large-scale simulations can provide a framework to systematically study the effects of several interacting disease parameters or effects from combinations of drugs.

Keywords: Biophysical model; C-fiber; Chronic pain; Compartment model; Computational neuropharmacology; Computational neuroscience; Hodgkin–Huxley model; Intrinsic excitability; Mechano-insensitive fiber; Na(v)1.7; Na(v)1.8; Na(v)1.9; Neuropathic pain; Nociception; Nociceptive axon; Peripheral nerve; Peripheral pain; Sensory nerve.