Spontaneous activity of nociceptors in the pathophysiology of neuropathic pain

Abstract

Polymodal and silent nociceptors supplying the skin and deep tissues are responsible for the generation and transmission of action potentials through unmyelinated fibres to brain through first and second order neurons. It has been shown that unmyelinated fibres conduct slow or fast depending on the previous status of the axon with a specific pattern. The method has allowed the differentiation between nociceptors and thermoreceptors by a protocol of electrical stimulation of their cutaneous receptive field. Importantly, the demonstration of fluctuations in otherwise stable latencies during regular low frequency stimulation, reflect spontaneous activity generated in the axon, an objective mechanism behind spontaneous pains. We will be discussing the technique of intraneural recording of single unmyelinated afferents in humans, with findings in experimental models of neuropathic pain and in disease states of painful neuropathy in which spontaneous activity and multiplication of impulses in first order neurons account for neuropathic pains. Future avenues to understand the mechanism of abnormal impulse generation in nociceptors will be debated.