Nociception Case File

Nociception Case File

EUGENE C.TOY, MD, RAHUL JANDIAL, MD, PhD, EVAN YALE SNYDER, MD, PhD, MARTIN T. PAUKERT, MD

CASE 20

A 75-year-old man came to his physician with complaints of a continuous severe, sharp, burning pain on the right hand side of his chest wall that extended around the right side onto his back. He stated that he initially felt numbness and tingling in this area before the pain began. The physician notes on examination that the area of skin corresponding to the pain is red, with several fluidfilled vesicles. The physician diagnoses the patient as having shingles (Herpes zoster), a viral disease which causes inflammation.

• What receptors are involved in feeling pain?
• What factors activate these receptors?
• Are there any available treatment options?

ANSWERS TO CASE 20: NOCICEPTION

Summary: A 75-year-old man has right chest wall, side, and back numbness and tingling that progresses to severe, sharp, burning pain. The corresponding area is red with fluid-filled vesicles. The affected area is sharply demarcated by dermatomal borders.

• Receptors: Nocireceptors
• Factors: Substance P, Histamine, and K+ are released after tissue damage or injury and activate the nocireceptors.
• Available treatment options: While there is no cure for herpes zoster, antiviral medications such as acyclovir can be effective in moderating the progress of symptoms, or can be taken prophylactically by those at high risk of developing the disease. A vaccine is now available to those who have never had a primary infection of the virus.

CLINICAL CORRELATION

Herpes zoster is a viral disease causing inflammation of the dorsal root ganglia along with severe pain and cutaneous eruption in the dermatomal distribution of the ganglion cells. The disease is caused by the varicella-zoster virus, which causes chickenpox during the first infection. The virus becomes latent in the dorsal root ganglion cells, and can reactivate later in life, frequently in people who are immunosuppressed. The severe pain results from the spread of the virus along the peripheral nerve fibers and the inflammation of neurons in the dorsal root ganglia that convey pain sensation.

APPROACH TO NOCICEPTION

Objectives

A. Know the different types of painful sensations.

B. Understand the importance of cerebral cortical processing of pain information to the perception of pain.

C. Be able to describe the endogenous analgesic system.

Definitions

Opioids: A chemical substance that can bind to the opioid receptors of the central nervous system providing pain relief.

Analgesia: Blocking of the conscious perception of pain.

Hyperesthesia: Abnormal increase in sensitivity to stimulation.

Hypesthesia: Abnormal decrease in sensitivity to stimulation.

Paresthesias: Spontaneous sensations of prickling, tingling, or numbness.

Radicular pain: Pain distributed over an area that is consistent with the boundaries of a dermatome.

Referred pain: Pain that is perceived in a surface area of the body far removed from its actual source.

Phantom pain: Pain that is felt in a part of the body that either no longer exists because of amputation or is insensate caused by nerve severance.

DISCUSSION

Pain is an unpleasant sensation that occurs in response to either an externally perceived event or an internal cognitive event. This unpleasant sensory and emotional perception associated with actual or potential tissue damage is to warn of avoidable or treatable injury. The sensations we describe as painful include pricking, burning, aching, stinging, and soreness. There are several aspects to pain which include a distinctive sensation, the individual’s reaction to this sensation, activity in both somatic and autonomic systems, and both reflex and volitional efforts of avoidance or escape.

Three types of pain sensation occur after an acute noxious event. Fast pain consists of a sharp, pricking sensation that can be localized accurately and results from activations of Aδ-myelinated fibers. Slow pain is a burning sensation that has a slower onset, greater persistence, a less clear location, and results from activation of unmyelinated C fibers. Slow pain runs through archispinothalamic and paleospinothalamic tracts, while fast pain runs through the neospinothalamic tract. Deep or visceral pain can be described as aching, burning, or cramping. Visceral pain results from stimulation of visceral and deep somatic receptors as in joints or muscles. Visceral receptors are innervated by both unmyelinated C fibers and myelinated Aδ fibers that pass through the sympathetic nerves. The cell bodies of both these fibers are located in the dorsal root ganglia.

The spinothalamic pathway, projecting to the VPL of the thalamus and from there to the primary somatosensory cortex, is essential for the spatial and temporal discrimination of painful stimuli. The spinoreticular pathways which connect to the secondary somatosensory cortex, hypothalamus, and limbic system, mediate systemic autonomic responses to pain and probably the emotional and affective responses as well. The cingulated cortex is one of the limbic areas activated by pain.

The cerebral cortex is an important component to the processing of pain. Patients who have suffered complete destruction of the somatosensory areas of the cerebral cortex on one side of the brain may still detect painful stimuli on the contralateral side of the body as long as the thalamus and lower structures of the pain pathway remain intact. Intractable pain can be relieved by destruction of the posterior and intralaminar nuclei of the thalamus. A prefrontal leukotomy transects the fibers linking the dorsomedial and anterior nuclei of the thalamus with the frontal lobe and anterior cingulated cortex, and can diminish the anguish of constant pain by changing the psychological response to painful stimuli. This lesion, however, is also accompanied by negative changes in personality and intellectual capacity. A cingulotomy, or bilateral section of the cingulum bundle, has been shown to relieve a patient’s reaction to pain without causing the drastic personality changes that occur with prefrontal leukotomy.

There are no pain receptors in the parenchyma of the internal organs, including the brain. The pain receptors are found within the walls of arteries, the peritoneal surfaces, pleural membranes, and the dura mater covering the brain. All of these structures can respond to inflammation or mechanical deformation with severe pain. Any abnormal contraction or dilatation of a wall of a hollow viscus, such as a blood vessel, also causes pain. The pain fibers from the viscera project to the spinal cord as components of the sympathetic nerves, while fibers conveying nonpainful visceral sensations project to the central nervous system as components of the parasympathetic nerves.

The afferent pathway of visceral pain receptors follows the peripheral sympathetic nerves from the viscera to the sympathetic trunk. Here they pass to the thoracic and lumbar spinal nerves over the white rami and enter the spinal cord. Their cell bodies are located in the dorsal root ganglia of segments T1 to L2, and their axons terminate at synapses in the dorsal horn of the intermediate gray matter. These nuclei project axons bilaterally through the anterolateral system to the brain stem reticular formation, intralaminar thalamic nuclei, and hypothalamus. Some visceral pain is also mediated by neurons from the deep central spinal gray matter whose axons ascend in the dorsal midline with the dorsal columns. These fibers terminate on neurons in the nuclei of the dorsal columns which then project to the ventral posterior thalamus.

Pain originating from the viscera tends to be vaguely localized. It may even be perceived in a surface area of the body far away from its actual source. This phenomenon is known as referred pain. A common example of referred pain occurs with pain of coronary heart disease, which may be felt in the chest wall, the left axilla, or down the inside of the left arm. Inflammation of the peritoneum covering the diaphragm may be felt over the shoulder. This occurs because the peripheral afferents that supply the skin area of the referred pain enter the same segment of the spinal cord as the visceral afferents conducting pain from the affected organ. Visceral sensory fibers discharge into the same pool of neurons in the spinal cord as fibers from the skin, and an abundance of impulses results in misinterpretation of the true origin of the pain. Noxious stimuli affecting deep somatic structures can result in referred pain as well.

Radicular pain is pain distributed over an area that is consistent with the boundaries of a dermatome. Mechanical compression or local inflammation of dorsal nerve roots can irritate pain fibers and produce pain along the dermatomal distribution of the affected root. Sensory changes other than pain may be associated with dorsal root irritation. Localized areas of spontaneous prickling, tingling, or numbness are termed paresthesias. Zones of hyperesthesia may be present in which tactile stimuli are grossly exaggerated. If the pathologic process progresses to the point of destroying the nerve fibers, the dorsal roots will eventually lose their ability to conduct sensory impulses, resulting in hypesthesia or anesthesia. The majority of skin areas receive innervation from fibers from more than one dorsal root, therefore, damage to a single dorsal root usually does not cause complete sensory loss (see Figure 20-1).

Figure 20-1. Components of a typical cutaneous nerve. (With permission from Harrison’s Principles of Internal Medicine. 15th ed. Fig. 11-1, Chap 11.)

Endogenous analgesia is an important component to understand in the treatment of pain. Stimulation of areas along the medial periventricular and periaqueductal axis, including the midline raphe nuclei of the brain stem, has been shown to produce analgesia. The raphe nuclei, found throughout the brain stem, are populated with neurons that produce serotonin. The axons of the caudal raphe nuclei descend to the spinal cord through the dorsolateral fasciculus. These axons terminate in the dorsal horn, where they attenuate the responses of spinothalamic cells to spinal nerve afferents mediating noxious stimuli from nociceptors. The release of opioid peptides is thought to primarily mediate endogenous analgesia. Other neurotransmitters such as serotonin, dopamine, and norepinephrine can also have analgesic effects. The three families of opioid receptors include enkephalin, β-endorphin, and dynorphin. Enkephalin interneurons are found in laminae I through III of the dorsal horn of the spinal cord. Inputs from descending serotonergic and noradrenergic fibers activate these interneurons and inhibit transmission of painful sensations at the first synaptic connection in the pain pathway.

COMPREHENSION QUESTIONS

[20.1] A 62-year-old man with high blood pressure and a 50-pack-year history of smoking develops sudden onset of chest and left arm pain one hot afternoon while mowing the lawn. He is rushed to the emergency department by his wife, where he is diagnosed with an acute MI. Therapy is begun immediately. What term is used to describe the pain this man felt in his arm during this event?

A. Central pain

B. Phantom pain

C. Radicular pain

D. Referred pain

[20.2] The back pain experienced by a 50-year-old man with pneumonia can best be classified as follows:

A. Radicular pain

B. Phantom pain

C. Referred pain

D. Central pain

[20.3] Following a thoracotomy and removal of a small lung nodule, one of your patients is complaining of severe pain at the incision site and underlying chest wall. The standard doses of pain medication do not seem to have the desired result, and you are afraid to give too much for fear of oversedating him. To more adequately control this patient’s pain you decide to start him on a morphine PCA (patientcontrolled analgesia) pump. This works very well, and by the following morning he has no further complaints of pain. Through what mechanism does morphine decrease pain?

A. Blocking sensory nerve action potentials

B. Modulating the brain and spinal cord’s response to painful stimuli

C. Blocking pain transmission at the level of the thalamus

D. Preventing nerve endings from generating action potentials in response to normally painful stimuli

Answers

[20.1] D. This is an example of referred pain. The patient feels pain in his arm, but there is in fact no pathology affecting his arm. Instead, there is pathology affecting his heart, which is innervated by nerves from the same spinal levels as those innervating the arm. The afferent pain signal actually originating from the heart is erroneously interpreted as coming from the arm, resulting in referred pain. Central pain arises from a lesion in the thalamus or cortex that is interpreted as pain in the body part corresponding to the lesion. Phantom pain is “felt” in amputated limbs, and radicular pain is pain in the distribution of a spinal cord level caused by compression of the corresponding nerve root.

[20.2] C. Referred pain occurs when pain of visceral origin is localized to a part of the body far removed from the source. Inflammation of the pleura can frequently be referred to the thoracic dermatomes of the back.

[20.3] B. Morphine and other opioid pain medications decrease pain by modulating the brain and spinal cord’s response to painful stimuli. These molecules bind to receptor sites for endogenous opioids which are located in diffuse areas of the CNS, including in the brain and spinal cord. In the spinal cord, binding to opioid receptors modulates the response of second- and third-order neurons in the pain pathway to painful stimuli coming in from the periphery. Opioid receptors in the brainstem activate descending tracts that further modulate pain transmission in the spinal cord. Through poorly understood mechanisms, opiates also result in altering the perception of pain, that is, the sensation of pain is still there, but it is not as debilitating

NEUROSCIENCE PEARLS ❖ Three types of pain sensations occur after an acute noxious event: (1) fast pain, (2) slow pain, and (3) visceral pain. ❖ Fast pain is an accurately localizable, immediate, sharp sensation resulting from activation of myelinated Aδ fibers. ❖ Slow pain is a vaguely localizable, burning pain resulting from activation of unmyelinated C fibers. ❖ Visceral pain is an aching pain resulting from stimulation of deep somatic receptors in joints or muscles which are innervated by both C and Aδ fibers. ❖ Stimulation of areas along the medial periventricular and periaqueductal axis has been shown to produce analgesia.

REFERENCES

Basbaum AI, et al. Smell and taste: the perception of pain. In: Kandel ER, et al., Principles of Neural Science. 4th ed. New York, NY: McGraw-Hill; 2000. 

Martin JH. The somatic sensory system. Neuroanatomy, Text and Atlas. 2nd ed. Stamford, CT: Appleton & Lange; 1996. 

Ropper AH, et al. Pain. Adam’s and Victor’s Principles of Neurology. 8th ed. New York, NY: McGraw-Hill; 2005.

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