Somatic Sensations: II. Pain, Headache, and Thermal Sensations

Pain Receptors Are Free Nerve Endings

The pain receptors in the skin and other tissues are all free nerve endings. They are widespread in the superficial layers of the skin, as well as in certain internal tissues, such as the periosteum, the arterial walls, the joint surfaces, and the falx and tentorium in the cranial vault. Most other deep tissues are only sparsely supplied with pain endings; nevertheless, any widespread tissue damage can summate to cause the slow, chronic, aching type of pain in most of these areas.

Mechanical, Thermal, and Chemical Stimuli Excite Pain Receptors

Pain can be elicited by multiple types of stimuli, classified as mechanical, thermal, and chemical pain stimuli. In general, fast pain is elicited by the mechanical and thermal types of stimuli, whereas slow pain can be elicited by all three types.

Some of the chemicals that excite the chemical type of pain are bradykinin, serotonin, histamine, potassium ions, acids, acetylcholine, and proteolytic enzymes. In addition, prostaglandins and substance P enhance the sensitivity of pain endings but do not directly excite them. The chemical substances are especially important in stimulating the slow suffering type of pain that occurs after tissue injury.

Nonadapting Nature of Pain Receptors

In contrast to most other sensory receptors of the body, pain receptors adapt very little and sometimes not at all. In fact, under some conditions, excitation of pain fibers becomes progressively greater, especially for slow, aching, nauseous pain, as the pain stimulus continues. This increase in sensitivity of the pain receptors is called hyperalgesia. One can readily understand the importance of this failure of pain receptors to adapt because it allows the pain to keep the person apprised of a tissue-damaging stimulus as long as it persists.

Rate of Tissue Damage as a Stimulus for Pain

The average person begins to perceive pain when the skin is heated above 45°C, as shown in Figure 49-1 . This is also the temperature at which the tissues begin to be damaged by heat; indeed, the tissues are eventually destroyed if the temperature remains above this level indefinitely. Therefore, it is immediately apparent that pain resulting from heat is closely correlated with the rate at which damage to the tissues is occurring and not with the total damage that has already occurred.

The intensity of pain is also closely correlated with the rate of tissue damage from causes other than heat, such as bacterial infection, tissue ischemia, tissue contusion, and so forth.

Special Importance of Chemical Pain Stimuli During Tissue Damage

Extracts from damaged tissue cause intense pain when injected beneath the normal skin. Most of the chemicals listed earlier that excite the chemical pain receptors can be found in these extracts. One chemical that seems to be more painful than others is bradykinin. Researchers have suggested that bradykinin might be the agent most responsible for causing pain after tissue damage. Also, the intensity of the pain felt correlates with the local increase in potassium ion concentration or the increase in proteolytic enzymes that directly attack the nerve endings and excite pain by making the nerve membranes more permeable to ions.

Tissue Ischemia as a Cause of Pain

When blood flow to a tissue is blocked, the tissue often becomes very painful within a few minutes. The greater the rate of metabolism of the tissue, the more rapidly the pain appears. For example, if a blood pressure cuff is placed around the upper arm and inflated until the arterial blood flow ceases, exercise of the forearm muscles sometimes can cause muscle pain within 15 to 20 seconds. In the absence of muscle exercise, the pain may not appear for 3 to 4 minutes, even though the muscle blood flow remains zero.

One of the suggested causes of pain during ischemia is accumulation of large amounts of lactic acid in the tissues, formed as a consequence of anaerobic metabolism (i.e., metabolism without oxygen). It is also probable that other chemical agents, such as bradykinin and proteolytic enzymes, are formed in the tissues because of cell damage and that these agents, in addition to lactic acid, stimulate the pain nerve endings.

Muscle Spasm as a Cause of Pain

Muscle spasm is also a common cause of pain and is the basis of many clinical pain syndromes. This pain probably results partially from the direct effect of muscle spasm in stimulating mechanosensitive pain receptors, but it might also result from the indirect effect of muscle spasm to compress the blood vessels and cause ischemia. The spasm also increases the rate of metabolism in the muscle tissue, thus making the relative ischemia even greater, creating ideal conditions for the release of chemical pain-inducing substances.

Termination of the Neospinothalamic Tract in the Brain Stem and Thalamus

A few fibers of the neospinothalamic tract terminate in the reticular areas of the brain stem, but most pass all the way to the thalamus without interruption, terminating in the ventrobasal complex along with the dorsal column–medial lemniscal tract for tactile sensations, as was discussed in Chapter 48 . A few fibers also terminate in the posterior nuclear group of the thalamus. From these thalamic areas, the signals are transmitted to other basal areas of the brain, as well as to the somatosensory cortex.

The Nervous System Can Localize Fast Pain in the Body

The fast-sharp type of pain can be localized much more exactly in the different parts of the body than can slow-chronic pain. However, when only pain receptors are stimulated, without the simultaneous stimulation of tactile receptors, even fast pain may be poorly localized, often only within 10 centimeters or so of the stimulated area. Yet, when tactile receptors that excite the dorsal column–medial lemniscal system are simultaneously stimulated, the localization can be nearly exact.

Glutamate, the Probable Neurotransmitter of the Type Aδ Fast Pain Fibers

It is believed that glutamate is the neurotransmitter substance secreted in the spinal cord at the type Aδ pain nerve fiber endings. Glutamate is one of the most widely used excitatory transmitters in the central nervous system, usually having a duration of action lasting for only a few milliseconds.

Substance P, the Probable Slow-Chronic Neurotransmitter of Type C Nerve Endings

Type C pain fiber terminals entering the spinal cord release both glutamate transmitter and substance P transmitter. The glutamate transmitter acts instantaneously and lasts for only a few milliseconds. Substance P is released much more slowly, building up in concentration over a period of seconds or even minutes. In fact, it has been suggested that the “double” pain sensation one feels after a pinprick might result partly from the fact that the glutamate transmitter gives a faster pain sensation, whereas the substance P transmitter gives a more lagging sensation. Regardless of the yet unknown details, it seems clear that glutamate is the neurotransmitter most involved in transmitting fast pain into the central nervous system, and substance P is concerned with slow-chronic pain.

Projection of Paleospinothalamic Pathway (Slow-Chronic Pain Signals) into the Brain Stem and Thalamus

The slow-chronic paleospinothalamic pathway terminates widely in the brain stem, in the large shaded area shown in Figure 49-3 . Only 10% to 25% of the fibers pass all the way to the thalamus. Instead, most terminate in one of three areas: (1) the reticular nuclei of the medulla, pons, and mesencephalon; (2) the tectal area of the mesencephalon deep to the superior and inferior colliculi; or (3) the periaqueductal gray region surrounding the aqueduct of Sylvius. These lower regions of the brain appear to be important for feeling the suffering types of pain. From the brain stem pain areas, multiple short-fiber neurons relay the pain signals upward into the intralaminar and ventrolateral nuclei of the thalamus and into certain portions of the hypothalamus and other basal regions of the brain.

Poor Capability of the Nervous System to Localize Precisely the Source of Pain Transmitted in the Slow-Chronic Pathway

Localization of pain transmitted via the paleospinothalamic pathway is imprecise. For example, slow-chronic pain can usually be localized only to a major part of the body, such as to one arm or leg but not to a specific point on the arm or leg. This phenomenon is in keeping with the multisynaptic, diffuse connectivity of this pathway. It explains why patients often have serious difficulty in localizing the source of some chronic types of pain.

Function of the Reticular Formation, Thalamus, and Cerebral Cortex in the Appreciation of Pain

Complete removal of the somatic sensory areas of the cerebral cortex does not prevent pain perception. Therefore, it is likely that pain impulses entering the brain stem reticular formation, the thalamus, and other lower brain centers cause conscious perception of pain. This does not mean that the cerebral cortex has nothing to do with normal pain appreciation; electrical stimulation of cortical somatosensory areas does cause a person to perceive mild pain from about 3% of the points stimulated. However, it is believed that the cortex plays an especially important role in interpreting pain quality, even though pain perception might be principally the function of lower centers.