How are nociceptors sensitized

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How are nociceptors sensitized? 

After a burn of the skin, for example, inflammatory mediators are released at the injured tissue site.

These include prostaglandins, bradykinin, protons, and cytokines. The local inflammatory milieu also triggers nociceptors to release substance P and calcitonin gene-related peptide (CGRP).

These substances promote further vasodilation and facilitate the migration of inflammatory cells such as neutrophils and macrophages.

Phosphorylation of the ionic channels makes these ionic channels more permeable to depolarizing ions like sodium and calcium, resulting in nerve hyperexcitability and nociceptor sensitization.

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