Hyperalgesia Physiology

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Figure 48-6


Liver and gallbladder



Appendix and small intestine

Right kidney

Left kidney

Colon Ureter

Surface areas of referred pain from different visceral organs.

Visceral Pain Signal

Visceral and parietal transmission of pain signals from the appendix.

the dual transmission of pain through the referred visceral pathway and the direct parietal pathway. Thus, Figure 48-7 shows dual transmission from an inflamed appendix. Pain impulses pass first from the appendix through visceral pain fibers located within sympathetic nerve bundles, and then into the spinal cord at about T-10 or T-11; this pain is referred to an area around the umbilicus and is of the aching, cramping type. Pain impulses also often originate in the parietal peritoneum where the inflamed appendix touches or is adherent to the abdominal wall. These cause pain of the sharp type directly over the irritated peritoneum in the right lower quadrant of the abdomen.

Some Clinical Abnormalities of Pain and Other Somatic Sensations


A pain nervous pathway sometimes becomes excessively excitable; this gives rise to hyperalgesia, which means hypersensitivity to pain. Possible causes of hyperalgesia are (1) excessive sensitivity of the pain receptors themselves, which is called primary hyperalgesia, and (2) facilitation of sensory transmission, which is called secondary hyperalgesia.

An example of primary hyperalgesia is the extreme sensitivity of sunburned skin, which results from sensitization of the skin pain endings by local tissue products from the burn—perhaps histamine, perhaps prostaglandins, perhaps others. Secondary hyperalgesia frequently results from lesions in the spinal cord or the thalamus. Several of these lesions are discussed in subsequent sections.

Herpes Zoster (Shingles)

Occasionally herpesvirus infects a dorsal root ganglion. This causes severe pain in the dermatomal segment subserved by the ganglion, thus eliciting a segmental type of pain that circles halfway around the body.The disease is called herpes zoster, or "shingles," because of a skin eruption that often ensues.

The cause of the pain is presumably infection of the pain neuronal cells in the dorsal root ganglion by the virus. In addition to causing pain, the virus is carried by neuronal cytoplasmic flow outward through the neuronal peripheral axons to their cutaneous origins. Here the virus causes a rash that vesiculates within a few days and then crusts over within another few days, all of this occurring within the dermatomal area served by the infected dorsal root.

Tic Douloureux

Lancinating pain occasionally occurs in some people over one side of the face in the sensory distribution area (or part of the area) of the fifth or ninth nerves; this phenomenon is called tic douloureux (or trigeminal neuralgia or glossopharyngeal neuralgia). The pain feels like sudden electrical shocks, and it may appear for only a few seconds at a time or may be almost continuous. Often it is set off by exceedingly sensitive trigger areas on the surface of the face, in the mouth, or inside the throat—almost always by a mechanoreceptive stimulus rather than a pain stimulus. For instance, when the patient swallows a bolus of food, as the food touches a tonsil, it might set off a severe lancinating pain in the mandibular portion of the fifth nerve.

The pain of tic douloureux can usually be blocked by surgically cutting the peripheral nerve from the hypersensitive area. The sensory portion of the fifth nerve is often sectioned immediately inside the cranium, where the motor and sensory roots of the fifth nerve separate from each other, so that the motor portions, which are needed for many jaw movements, can be spared while the sensory elements are destroyed. This operation leaves the side of the face anesthetic, which in itself may be annoying. Furthermore, sometimes the operation is unsuccessful, indicating that the lesion that causes the pain might be in the sensory nucleus in the brain stem and not in the peripheral nerves.

Brown-Sequard Syndrome

If the spinal cord is transected entirely, all sensations and motor functions distal to the segment of transection are blocked, but if the spinal cord is transected on only one side, the Brown-Sequard syndrome occurs. The effects of such transection can be predicted from a knowledge of the cord fiber tracts shown in Figure 48-8. All motor functions are blocked on the side of the tran-section in all segments below the level of the transec-tion. Yet only some of the modalities of sensation are lost on the transected side, and others are lost on the opposite side. The sensations of pain, heat, and cold— sensations served by the spinothalamic pathway—are lost on the opposite side of the body in all dermatomes two to six segments below the level of the transection. By contrast, the sensations that are transmitted only in the dorsal and dorsolateral columns—kinesthetic and position sensations, vibration sensation, discrete localization, and two-point discrimination—are lost on the side of the transection in all dermatomes below the level of the transection. Discrete "light touch" is impaired on the side of the transection because the principal pathway for the transmission of light touch, the dorsal column, is transected. That is, the fibers in this column do not cross to the opposite side until they reach the medulla of the brain. "Crude touch," which is poorly localized, still persists because of partial transmission in the opposite spinothalamic tract.


Headaches are a type of pain referred to the surface of the head from deep head structures. Some headaches result from pain stimuli arising inside the cranium, but others result from pain arising outside the cranium, such as from the nasal sinuses.

Headache of Intracranial Origin

Pain-Sensitive Areas in Cranial Vault. The brain tissues themselves are almost totally insensitive to pain. Even cutting or electrically stimulating the sensory areas of the cerebral cortex only occasionally causes pain; instead, it causes prickly types of paresthesias on the area of the body represented by the portion of the sensory cortex stimulated. Therefore, it is likely that much or most of the pain of headache is not caused by damage within the brain itself.

Conversely, tugging on the venous sinuses around the brain, damaging the tentorium, or stretching the dura at the base of the brain can cause intense pain that is recognized as headache. Also, almost any type of traumatizing, crushing, or stretching stimulus to the blood vessels of the meninges can cause headache. An especially sensitive structure is the middle meningeal artery, and neurosurgeons are careful to anesthetize this artery specifically when performing brain operations under local anesthesia.

Areas of the Head to Which Intracranial Headache Is Referred.

Stimulation of pain receptors in the cerebral vault above the tentorium, including the upper surface of the tentorium itself, initiates pain impulses in the cerebral portion of the fifth nerve and, therefore, causes referred headache to the front half of the head in the surface areas supplied by this somatosensory portion of the fifth cranial nerve, as shown in Figure 48-9.

Conversely, pain impulses from beneath the tentorium enter the central nervous system mainly through the glossopharyngeal, vagal, and second cervical nerves, which also supply the scalp above, behind, and slightly below the ear. Subtentorial pain stimuli cause "occipital headache" referred to the posterior part of the head.

Headaches are a type of pain referred to the surface of the head from deep head structures. Some headaches

Cross section of the spinal cord, showing principal ascending tracts on the right and principal descending tracts on the left.

Areas of headache resulting from different causes.

Cross section of the spinal cord, showing principal ascending tracts on the right and principal descending tracts on the left.

Areas of headache resulting from different causes.

Types of Intracranial Headache

Headache of Meningitis. One of the most severe headaches of all is that resulting from meningitis, which causes inflammation of all the meninges, including the sensitive areas of the dura and the sensitive areas around the venous sinuses. Such intense damage can cause extreme headache pain referred over the entire head.

Headache Caused by Low Cerebrospinal Fluid Pressure.

Removing as little as 20 milliliters of fluid from the spinal canal, particularly if the person remains in an upright position, often causes intense intracranial headache. Removing this quantity of fluid removes part of the flotation for the brain that is normally provided by the cerebrospinal fluid. The weight of the brain stretches and otherwise distorts the various dural surfaces and thereby elicits the pain that causes the headache.

Migraine Headache. Migraine headache is a special type of headache that is thought to result from abnormal vascular phenomena, although the exact mechanism is unknown. Migraine headaches often begin with various prodromal sensations, such as nausea, loss of vision in part of the field of vision, visual aura, and other types of sensory hallucinations. Ordinarily, the prodromal symptoms begin 30 minutes to 1 hour before the beginning of the headache. Any theory that explains migraine headache must also explain the prodromal symptoms.

One of the theories of the cause of migraine headaches is that prolonged emotion or tension causes reflex vasospasm of some of the arteries of the head, including arteries that supply the brain. The vasospasm theoretically produces ischemia of portions of the brain, and this is responsible for the prodromal symptoms. Then, as a result of the intense ischemia, something happens to the vascular walls, perhaps exhaustion of smooth muscle contraction, to allow the blood vessels to become flaccid and incapable of maintaining vascular tone for 24 to 48 hours. The blood pressure in the vessels causes them to dilate and pulsate intensely, and it is postulated that the excessive stretching of the walls of the arteries—including some extracranial arteries, such as the temporal artery—causes the actual pain of migraine headaches. Other theories of the cause of migraine headaches include spreading cortical depression, psychological abnormalities, and vasospasm caused by excess local potassium in the cerebral extracellular fluid.

There may be a genetic predisposition to migraine headaches, because a positive family history for migraine has been reported in 65 to 90 per cent of cases. Migraine headaches also occur about twice as frequently in women as in men.

Alcoholic Headache. As many people have experienced, a headache usually follows an alcoholic binge. It is most likely that alcohol, because it is toxic to tissues, directly irritates the meninges and causes the intracra-nial pain.

Headache Caused by Constipation. Constipation causes headache in many people. Because it has been shown that constipation headache can occur in people whose pain sensory tracts in the spinal cord have been cut, we know that this headache is not caused by nervous impulses from the colon. Therefore, it may result from absorbed toxic products or from changes in the circulatory system resulting from loss of fluid into the gut.

Extracranial Types of Headache

Headache Resulting from Muscle Spasm. Emotional tension often causes many of the muscles of the head, especially those muscles attached to the scalp and the neck muscles attached to the occiput, to become spastic, and it is postulated that this is one of the common causes of headache. The pain of the spastic head muscles supposedly is referred to the overlying areas of the head and gives one the same type of headache as intracranial lesions do.

Headache Caused by Irritation of Nasal and Accessory Nasal Structures. The mucous membranes of the nose and nasal sinuses are sensitive to pain, but not intensely so. Nevertheless, infection or other irritative processes in widespread areas of the nasal structures often summate and cause headache that is referred behind the eyes or, in the case of frontal sinus infection, to the frontal surfaces of the forehead and scalp, as shown in Figure 48-9. Also, pain from the lower sinuses, such as from the maxillary sinuses, can be felt in the face.

Headache Caused by Eye Disorders. Difficulty in focusing one's eyes clearly may cause excessive contraction of the eye ciliary muscles in an attempt to gain clear vision. Even though these muscles are extremely small, it is believed that tonic contraction of them can cause retro-orbital headache. Also, excessive attempts to focus the eyes can result in reflex spasm in various facial and extraocular muscles, which is a possible cause of headache.

A second type of headache that originates in the eyes occurs when the eyes are exposed to excessive irradiation by light rays, especially ultraviolet light. Looking at the sun or the arc of an arc-welder for even a few seconds may result in headache that lasts from 24 to 48 hours. The headache sometimes results from "actinic" irritation of the conjunctivae, and the pain is referred to the surface of the head or retro-orbitally. However, focusing intense light from an arc or the sun on the retina can also burn the retina, and this could be the cause of the headache.

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