The nociceptive pathway can be initiated by direct peripheral nerve damage or by the action of chemical mediators. Such chemical mediators include factors such as prostaglandins (PG) and kinins, which are released as a result of tissue damage. These substances not only initiate nociception, but also activate the inflammatory process by inducing the following changes:
• Increases in local blood flow and vascular permeability
• Activation and migration of immune cells
• Release of growth and trophic factors from surrounding tissues
Thus a complex set of events is involved which can produce changes in afferent neurones ranging from sensitization to alterations in morphology (Figure NE.15).
There are two principal mechanisms by which inflammatory mediators influence neuronal activities:
• Direct action on membrane ion channel proteins thereby changing membrane permeability and cellular excitability (e.g. 5-hydroxytryptamine [5-HT], protons)
• Interaction with membrane receptors which are coupled to the activities of second messengers such as cAMP and/or G proteins (e.g. adenosine, bradykinin [BK], 5-HT, prostanoids). This in turn may lead to structural changes in membrane ion channels or changes in the activity of intracellular enzymes affecting membrane excitability
Other neuropeptides are also known to be involved in nociception. Unmyelinated afferent neurones contain several neuropeptides, such as Substance P (SP) and calcitonin gene-related peptide (CGRP), which also play an important role in pathogenesis of pain. The possible mechanisms whereby inflammatory mediators may produce pain are summarized in Figure NE.16.
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