Chapter 44, Problem 1O

Summary Introduction

To discuss:

The inflammatory response and the part it plays in the generation of pain.

Concept Introduction:

Inflammation is the localized process initiated due to the injury or infection in the tissues. Tissue cells produce inflammatory cytokines such as (leukotrienes, bradykinin, histamine, and so on) that lead to the migration of macrophage immune cells to the injured tissue site and cause phagocytosis, which is an inflammatory-mediated response. Inflammation has a series of pathways involved. The common symptoms found in inflammation are pain and swelling.

Explanation of Solution

Pictorial representation:

Figure: Inflammatory pathways

The first and foremost step in the inflammation is triggering the inflammatory pathway mediated by the endogenous compounds present inside the host such as histamine, leukotrienes, prostaglandins, serotonin, and histamines. These endogenous compounds are collectively called as inflammatory compounds. There are two different modes of inflammatory pathways. One is leukotriene pathway and the other is prostaglandin pathway.

The common precursor phospholipid in the cell membrane is transformed to arachidonic acid mediated by phospholipase enzyme as a trigger during tissue injury. Phospholipase is an important inflammatory mediatory enzyme. Arachidonic acid enters the inflammatory pathway either by leukotriene or prostaglandin pathway.

Leukotriene pathway:

Leukotrienes are the eicosanoid mediated inflammatory agents. Arachidonic acid is metabolized into inflammatory leukotrienes such as LTA₄, LTB₄, LTC₄, LTD_4, and LTE_4, which is mediated by the lipoxygenase enzyme. Those leukotrienes LTA₄, LTB₄, LTC₄, LTD_4, and LTE₄ cause inflammation and pain by means of vasoconstriction, bronchoconstriction, and vascular permeability.

Prostaglandin pathway:

In this pathway, arachidonic acid is converted into prostaglandins like prostacyclin (PGl₂), and thromboxane (TXA₂), by the cyclooxygenase enzyme.  These prostaglandins, in turn, mediate the production of proinflammatory cytokines such as histamines, and bradykinin, which induces the pain and edema. The occurrence of fever during inflammation is mediated by Prostaglandin E2 synthesized in the hypothalamus region. Prostaglandin-mediated inflammatory pathway brings vasoconstriction, vasodilation, and platelet aggregation in the host.

Conclusion

The inflammatory response is a body natural defense mechanism by which the tissue injury caused by endogenous substances such as pathogens, inflammatory agents are eliminated by the phagocytes. Macrophage cells migrate toward the inflammation site and execute the phagocytosis process. Vasoconstriction, vasodilation, and platelet aggregation during inflammatory pathways cause pain and edema at the inflammatory site.