6. Pain Principles
Part 3 of 3

Nachum Dafny, Ph.D.
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Two sequential pain sensations in short time intervals is the result of sudden painful stimulation. The first one is immediately after the damage. It is followed several seconds later with additional pain sensation. These two separate sensations are several seconds apart because a fast transmitting information sensation is carried via A delta fibers and is followed several seconds later with slow transmitting pain information carried via C fibers. This phenomenon is known as “double pain sensation” (Figure 6.9).

Two experimental procedures were used to verify which information is carried by which fibers.

1. Externally applied pressure, such as compression of the skin above a nerve, first blocks the myelinated A delta fibers, while C fibers continue to conduct action potentials and allow the slow conducting pain to be carried.
2. A low dose of local anesthesia applied to peripheral nerves blocks the unmyelinated C fibers before the myelinated A delta fibers. Under this condition, the slow conducting pain information is blocked, and only the fast conducting pain information by A delta fibers is carried to the CNS. This experiment provides additional evidence that two different types of nerve fibers carry noxious information.

The synaptic terminals of the axons of the dorsal root ganglion, which carry noxious information arriving to Rexed layers I and II (Figure 6.10), release neurochemical agents such as substance P (SP), glutamate, aspartate, vasoactive intestinal peptide (VIP), cholecystokinin (CCK), somatostatin, calcitonin gene-related peptide (CGRP), galanin, and other agents. These agents activate the nocineurons. It was shown that when SP and CGRP are applied locally within the spinal cord dorsal horn, glutamate is released. The release of glutamate excites the nocineurons. Furthermore, SP receptors (neurokinin receptors) and NMDA receptors (glutamate) interact which result that the NMDA receptors will become more sensitive to glutamate, which results in central sensitization. The functions of these peptides are largely unknown but they presumably mediate slow, modulatory synaptic actions in the dorsal horn neurons. The neuropeptides are always co-localized with other "classical" neurotransmitters.

There are four general types of nocineurons in the spinal cord (Figure 6.10):

1. High threshold mechanoreceptor neurons or nociceptive specific neurons. These neurons are excited only by noxious cutaneous and/or visceral stimuli. The nociceptive afferent fibers release glutamate and different neuropeptides to activate the dorsal horn neurons.
2. Chemical nociceptor neurons are excited by chemical or thermal noxious stimulus in the skin or in visceral organs.
3. Thermal nociceptor neurons are excited by chemical or thermal noxious stimulus in the skin or in visceral organs.
4. Polymodal-nociceptive neurons or multi, or wide dynamic range nociceptive neurons. These neurons are excited by both noxious and non-noxious cutaneous and/or visceral stimuli (polymodal nociceptive neurons). These neurons are activated by a variety of noxious stimuli (mechanical, thermal, chemical, etc.) and respond incrementally to increasing intensity of the stimuli.

Rexed lamina I contains a higher proportion of nociceptive specific neurons, whereas Rexed lamina II contains predominantly multi-receptive wide dynamic range neurons. The nociceptive-specific neurons alert the subject when a stimulus is noxious, and the multi-receptive neurons provide the subject with information about the parameters of the noxious stimulus. In general, C fibers release neuropeptides such as substance P whereas the A delta fibers release glutamate.  

Pain has been classified into three major types:

1. Pricking pain. Pain caused by a needle, pin prick, skin cut, etc. - elicits a sharp, pricking quality, stinging pain sensation carried fast by the A delta fibers. The pain is precisely localized and of short duration. Pricking pain is also called fast pain, first pain or sensory pain. Pricking pain is present in all individuals and is a useful and necessary component of our sensory repertoire. Without this type of protective pain sensation, everyday life would be difficult. Pricking pain arises mainly from the skin, and carried mainly by A delta fibers which permits discrimination (i.e., permits the subject to localize the pain).
2. Burning pain or soreness pain. Pain caused by inflammation, burned skin, etc., is carried by the C fibers (slowly conducted pain nerve fibers). This type of pain is a more diffuse, slower to onset, and longer in duration. It is an annoying pain and intolerable pain, which is not distinctly localized. Like pricking pain, burning pain arises mainly from the skin. It is carried by the paleospinothalamic tract. (The old primitive transmission system for diffuse pain which does not permit exact localization.)
3. Aching pain is a sore pain. This pain arises mainly from the viscera and somatic deep structures. Aching pain is not distinctly localized and is an annoying and intolerable pain. Aching pain is carried by the C fibers from the deep structures to the spinal cord.

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