Table 19-1 Tissue chemicals affecting polymodal nociceptors

Compound Origin Mechanism of action Mode of action on nociceptive fiber
Protons (acid) Tissue metabolism. Increased ion conductance. Activation.
Potassium Injured cells. Direct effect on membrane potential. Activation.
Adenosine triphosphate Tissue cells. Increased ion conductance. Activation.
Bradykinin Tissue protease cleves kininogen. Receptor acts through second messengers. Activates through second messengers.
Histamine Mast cells (release triggered by substance P). Vasodilation and increased vascular permiability. Activates pain fibers in high concentration; allows substances to enter tissues.
Eicosanoids (prostaglandin) Many cells when injured (including nerve terminals). Receptor inked to second messenger (cyclic AMP). Mainly a sensitizer of nociceptors.
Leukotrines From cells of immune system. Trigger release of pain-producing compounds from other cells. Acts indirectly.
Cytokines (e.g., interleukin, tumor necrosis factor, interferons, etc.) From cells of immune system. Probably act by causing synthesis of other compounds (such as prostaglandin). Acts indirectly.
Substance P From nociceptive afferent nerve fibers. Works by causing release of histamine, serotonin and prostaglandin as well as release of leukotrines and cytokines. Acts indirectly.
Catecholamines Sympathetic nerve terminals. Increases tissue prostaglandin synthesis and may directly activate injured axons. Mostly acts indirectly.
Nerve growth factors Produced in inflamed tissues. Alters gene expression in sensory nerve fibers. Acts indirectly.
Serotonin Platelets and mast cells. Receptor subtypes (both ion channel and second-messenger). Sensitization more important than direct activation; increase calcium currents via second messengers.
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