An injured area is typically more sensitive to subsequent stimuli. As a result, painful stimuli, or even normally nonpainful stimuli, may cause an excessive pain response. An increase in the sensitivity of nociceptors is referred to as primary hyperalgesia. A classic example of hyperalgesia is a burn. Even light touch of a burned area may be painful.

The sensitization of nociceptors following tissue damage or inflammation results from a variety of chemicals released or activated in the injured area (see Table 8.1). These substances decrease the threshold for activation of the nociceptors. One such substance that seems to be more painful than the others is bradykinin. Activated by enzymes released from damaged cells, bradykinin causes pain by several mechanisms. First, it activates A-delta and C fibers directly. Second, along with histamine, it contributes to the inflammatory response to tissue injury. Third, it promotes synthesis and release of prostaglandins from nearby cells. The prostaglandins sensitize all three types of pain receptors, thus enhancing the response to a noxious stimulus. In other words, it hurts more when prostaglandins are present. Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the synthesis of prostaglandins, which accounts, in part, for their analgesic effects.

Centrally mediated hyperalgesia involves the hyperexcitability of second-order sensory neurons in the dorsal horn of the spinal cord. In the case of severe or persistent tissue injury, C fibers fire action potentials repetitively. As a result, response of the second-order sensory neurons increases progressively. The mechanism of this enhanced response, also referred to as "wind-up," depends on the release of the neurotransmitter glutamate from the C fibers. An excitatory neurotransmitter, glutamate stimulates the opening of calcium channels gated by the N-methyl-D-aspartate (NMDA)-type glutamate receptor. Calcium influx ultimately leads to long-term biochemical changes and hyperexcitability of the second-order neuron.

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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