Reading: Haines, Ch. 17; Handout
thermal nociceptors: Fall into two classes, those activated by heat (35-45 degrees C) and those activated by cold (17-35 degrees C). With repeated stimulation, these receptors become sensitized and show a decreased threshold and larger response to the application of a stimulus. Levels of heat >45C or cold <17C that burn the skin produce high-frequency firing in both A-delta and C thermonociceptors (Haines 239)
mechanoreceptors: Group A-delta and C mechanonociceptors. Respond to mechanical tissue damage (Haines 239). They are conveyed by ALS pathways. This system transmits signals originating in peripheral receptors to spinal cord and brainstem neurons. These signals are then forwarded to thalamic nuclei and from there to the proper representation area on the somatosensory cortex (Haines 238).
polymodal receptors: Class C fibers that respond to mechanical, thermal, and chemical stimuli (Haines 239)
primary hyperalgesia: Excessive sensitivity of the pain receptors themselves. An example would be getting a sunburn. She skin is extremely sensitive . The sensitization of the pain endings by local tissue products of the burn -- perhaps histamine, and/or prostaglandins or others (Guyton 616). It is from the inflammatory process--where the damage actually occurs (class notes).
secondary hyperalgesia: Facilitation of sensory transmission. Frequently results from lesions in the spinal cord or the thalamus (Guyton 616). It is usually mechanical stimuli. The neurons in the spinal cord have an increased sensitivity (class notes).
visceral pain: In general, the viscera have sensory receptors for no other modalities of sensation besides pain. Highly localized types of damage to the viscera seldom cause severe pain. Any stimulus that excites pain nerve endings in diffuse areas of the viscera causes visceral pain. Such stimuli include ischemia of visceral tissue, chemical damage to the surfaces of the viscera, spasm of the smooth muscle in a hollow viscus, distention of a hollow viscus, and stretching of the ligaments. Visceral pain that originates in the thoracic and abdominal cavities is transmitted through pain nerve fibers that run in the autonomic nerves, mainly the sympathetic nerves. These fibers are small type C fibers and, therefore, can transmit only the chronic-aching-suffering type of pain (Guyton 615).
phantom pain: A phenomenon in which amputees have chronic pain in their nonexistent (amputated) limb; although not well understood, apparently the cut sensory nerves that previously transmitted inputs from the limb continue to respond to the trauma of amputation, and the brain interprets (projects) these painful stimuli as coming from the missing limb (Marieb 533).
central pain: Burning, aching, pricking, or lacerating and occurs in paroxysms that vary in intensity (Haines 251). It is pain that disappears and then returns later. Patients experiencing central pain may obtain temporary relief from "transcutaneous electrical nerve stimulation" (TENS), from electrical stimulation of the dorsal columns, or from chronic stimulation of the periaqueductal gray. Note: I think this is the same thing as Thalamic Pain below.
referred pain: Pain from the different viscera is frequently difficult to localize. Any pain that originates internally can be localized only generally. Much of the pain is sent from the viscera to the autonomic nerves. The sensation are "referred" to surface areas of the body often far from the painful organ (Guyton 615). For example, ischemia of the heart can be felt as pain to the left arm or neck etc. The pain stimuli is sent up to the same areas that deal with the Left arm/neck.
Convergence of visceral and somatic afferent fibers may account for referred pain. According to this hypothesis nociceptive afferent fibers from the viscera and afferents from specific somatic areas of the periphery converge on the same projection neurons in the dorsal horn. The brain has no way of knowing the actual source of the noxious stimulus and mistakenly identifies the sensation with the peripheral structure (from handout)
thalamic pain: Occasionally a small artery supplying blood to the posteroventral portion of the thalamus becomes blocked. The nuclei of this area degenerate while the rest of the thalamus nuclei remains intact. First all sensation on the opposite side of the body disappear. After a few weeks to a few months, some sensory perception in the opposite side of the body returns, but strong stimuli are usually necessary to elicit this. When the sensations do occur, they are poorly localized, almost always painful, sometimes lancinating, regardless of the type of stimulus applied tot the body (Guyton 616-617). Note: I think this is the same thing as Central Pain above.
herpes zoster: Occasionally a herpes virus infects a dorsal root ganglion. This causes severe pain in the dermatomal segment normally subserved by the ganglion, thus eliciting a segmental type of pain that circles halfway around the body. The cause of the pain is presumably excitation of the neuronal cells in the dorsal root ganglion by the virus infection (Guyton 617).
tic douloureux: Sharp, cutting pain occurs in some people over one side of the face in the sensory distribution area of the fifth or ninth nerves. The pain feels like sudden electric 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 in the throat--almost always by a mechanoreceptive stimulus instead of a pain stimulus. For example, 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 (Guyton 617).
headache: Headaches are referred pain to the surface of the head from the deep structures. Many headaches result from pain stimuli arising inside the cranium, but others result from pain arising outside the cranium, such as from the nasal sinuses (Guyton 617).
glutamate: The probable neurotransmitter of the Type A-delta fast pain fiber endings in the spinal cord. This is one of the most widely used excitatory transmitters in the central nervous system, usually having a period of action lasting for only a few milliseconds (Guyton 612).
non-NMDA receptor: non N-Methyl-D-Aspartate. Needs glutamate to depolarize the cell. Glutamate opens up the Na+ channels (From class notes).
NMDA receptor: N-Methyl-D-Aspartate. The membrane must be depolarized first THEN glutamate opens up and admits Na+ and Ca2+ (From class notes).
Substance P: The probable slow-chronic neurotransmitter of the Type C nerve endings. Glutamate is released immediately and Substance P is released much more slowly, building up in concentration over a period of seconds or even minutes (Guyton 612).
paleospinothalamic tract: The slow-chronic paleospinothalamic pathway terminates widely in the brain stem. Only 1/10 to 1/4 of the fibers pass all the way to the thalamus. Instead, they terminate principally 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. 3. The periaqueductal gray region (Guyton 612).
neospinothalamic tract: Used for Fast pain. The fast type A-delta pain fibers transmit mainly mechanical and acute thermal pain. They terminate mainly in lamina I of the dorsal horns and there excite second-order neurons of the neospinothalamic tract. These give rise to long fibers that cross immediately to the opposite side of the cord through the anterior commissure and then pass upward to the brain in the anterolateral columns. A few of these fibers terminate in the reticular areas of the brain stem, but most pass all the way to the thalamus, terminating in the ventrobasal complex along with the dorsal column-medial lemniscal tract for tactile sensations. From these areas, the signals area transmitted to other areas of the brain and to the somatic sensory cortex (Guyton 611).
gate control theory: A pain "gate" exists in the dorsal horn where impulses from small unmyelinated pain fibers and large touch (A-beta) fibers enter the cord. If impulses along the pain fibers outnumber those transmitted along the touch fibers, the gate opens and pain impulses are transmitted. If the reverse is true, the gate is closed by enkephalin-releasing interneurons in the spinal cord which inhibit transmission of both touch and pain impulses, thus reducing pain perception (Guyton 465).
periaqueductal gray: Natural opiate pathways that oversee descending pain suppressor fibers that synapse in the dorsal horns. When transmitting, these fibers produce analgesia, presumably by synapsing with opiate releasing interneurons that in turn actively inhibit forward transmission of pain inputs (Marieb 465).
nucleus raphe magnus: From these nuclei, the signals re transmitted down the dorsolateral columns in the spinal cord to a pain inhibitory complex located in the dorsal horns of the spinal cord. At this point, the analgesia signals can block the pain before it is relayed to the brain. Electrical stimulation of the raphe magnus (or periaqueductal gray matter) can almost completely suppress many strong pain signals entering by way of the dorsal spinal roots (Guyton 613).
nucleus paragigantocellularis: ????? Part of the analgesia system. (Guyton 613)
enkephalins: The body's natural opiate. It binds with opiate receptors producing analgesia. Activation of the analgesia system either by nervous signals entering the periaqueductal gray area and adjacent periventricular areas or by morphine-like drugs can totally or almost totally suppress many pain signals entering through the peripheral nerves (Guyton 614).
opiate receptors: Opiates binding with opiate receptors decrease the duration of the nociceptor's action potential, probably by decreased Ca2+ influx, and thus decrease the release of transmitter from primary afferent terminals. In addition, opiates hyperpolarize the membrane of the dorsal horn neurons by activating a K+ conductance. Opiates also decrease the amplitude of the post-synaptic potential (Class notes).
describe the stimuli that can activate the various types of nociceptors: Pain can be elicited by multiple types of stimuli. They are 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 include 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 (Guyton 609-610).
describe the main classes of nociceptors: Mechanical, Thermal & Chemical. See Above.
| Cutaneous Nociceptors | Mechanical, Thermal, and/or Chemical Stimuli |
| Mechanonociceptors Group A-delta Receptors Group C Receptors |
Mechanical tissue damage Mechanical tissue damage |
| Thermonociceptors A-delta Receptors A-delta and C Receptors |
Noxious heat and tissue damage Noxious cold and tissue damage |
| Chemonociceptors C Receptors |
Insect venom, bradykinin, histamine |
| Polymodal Nociceptors C Receptors |
Noxious heat/cold, tissue damage, algesic chemicals |
compare and contrast primary and secondary hyperalgesia: Hyperalgesia is hypersensitivity to pain. It is when a pain pathway becomes excessively excitable.
primary hyperalgesia: Excessive sensitivity of the pain receptors themselves. An example would be getting a sunburn. She skin is extremely sensitive . The sensitization of the pain endings by local tissue products of the burn -- perhaps histamine, and/or prostaglandins or others (Guyton 616). It is from the inflammatory process--where the damage actually occurs (class notes).
secondary hyperalgesia: Facilitation of sensory transmission. Frequently results from lesions in the spinal cord or the thalamus (Guyton 616). It is usually mechanical stimuli. The neurons in the spinal cord have an increased sensitivity (class notes).
name four types of pathological pain and proposed pathophysiological mechanisms:
thalamic pain: Occasionally a small artery supplying blood to the posteroventral portion of the thalamus becomes blocked. The nuclei of this area degenerate while the rest of the thalamus nuclei remains intact. First all sensation on the opposite side of the body disappear. After a few weeks to a few months, some sensory perception in the opposite side of the body returns, but strong stimuli are usually necessary to elicit this. When the sensations do occur, they are poorly localized, almost always painful, sometimes lancinating, regardless of the type of stimulus applied tot the body (Guyton 616-617). Note: I think this is the same thing as Central Pain above.
herpes zoster: Occasionally a herpes virus infects a dorsal root ganglion. This causes severe pain in the dermatomal segment normally subserved by the ganglion, thus eliciting a segmental type of pain that circles halfway around the body. The cause of the pain is presumably excitation of the neuronal cells in the dorsal root ganglion by the virus infection (Guyton 617).
tic douloureux: Sharp, cutting pain occurs in some people over one side of the face in the sensory distribution area of the fifth or ninth nerves. The pain feels like sudden electric 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 in the throat--almost always by a mechanoreceptive stimulus instead of a pain stimulus. For example, 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 (Guyton 617).
headache: Headaches are referred pain to the surface of the head from the deep structures. Many headaches result from pain stimuli arising inside the cranium, but others result from pain arising outside the cranium, such as from the nasal sinuses (Guyton 617).
explain the proposed mechanisms for referred pain: Pain from the different viscera is frequently difficult to localize. Any pain that originates internally can be localized only generally. Much of the pain is sent from the viscera to the autonomic nerves. The sensation are "referred" to surface areas of the body often far from the painful organ (Guyton 615). For example, ischemia of the heart can be felt as pain to the left arm or neck etc. The pain stimuli is sent up to the same areas that deal with the Left arm/neck.
Convergence of visceral and somatic afferent fibers may account for referred pain. According to this hypothesis nociceptive afferent fibers from the viscera and afferents from specific somatic areas of the periphery converge on the same projection neurons in the dorsal horn. The brain has no way of knowing the actual source of the noxious stimulus and mistakenly identifies the sensation with the peripheral structure (from handout)
describe the main ascending pathways of nociceptive information:
paleospinothalamic tract: The slow-chronic paleospinothalamic pathway terminates widely in the brain stem. Only 1/10 to 1/4 of the fibers pass all the way to the thalamus. Instead, they terminate principally 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. 3. The periaqueductal gray region (Guyton 612).
neospinothalamic tract: Used for Fast pain. The fast type A-delta pain fibers transmit mainly mechanical and acute thermal pain. They terminate mainly in lamina I of the dorsal horns and there excite second-order neurons of the neospinothalamic tract. These give rise to long fibers that cross immediately to the opposite side of the cord through the anterior commissure and then pass upward to the brain in the anterolateral columns. A few of these fibers terminate in the reticular areas of the brain stem, but most pass all the way to the thalamus, terminating in the ventrobasal complex along with the dorsal column-medial lemniscal tract for tactile sensations. From these areas, the signals area transmitted to other areas of the brain and to the somatic sensory cortex (Guyton 611).
spinoreticular:
spinomesencephalic:
explain the significance of the gate control theory: The extraordinary plasticity of human pain suggests that natral neural mechanisms must exist to modulate pain tranmission and perception. The "gate control theory" is one of the most significant advances in the understanding and management of pain.
gate control theory: A pain "gate" exists in the dorsal horn where impulses from small unmyelinated pain fibers and large touch (A-beta) fibers enter the cord. If impulses along the pain fibers outnumber those transmitted along the touch fibers, the gate opens and pain impulses are transmitted. If the reverse is true, the gate is closed by enkephalin-releasing interneurons in the spinal cord which inhibit transmission of both touch and pain impulses, thus reducing pain perception (Guyton 465).
describe the main descending control mechanisms for the modulation of pain perception, include anatomy, physiology, and neurotransmitters: Central structures implicated in the descending control of nociceptive transmission include:
- The somatosensory cortex
- The periventricular nucleus of the hypothalamus
- The pontine reticular formation
- Raphe nuclei and adjacent medullary reticular formation
Descending pathways originating in these structures are active during emergencies that could result in tissue damage.
Sites in the brainstem and hypothalamus modulate the processing of nociceptive information in the brainstem and spinal cord. The periventricular gray of the hypothalamus communicates with the periaqueductal gray (PAG) of the midbrain via an enkaphalinergic pathway. Descending PAG fibers exert an excitatory influence on serotinergic neurons in the medullary nucleus raphe magnus, both directly and through interneurons in the lateral medullary reticular formation. This projection uses serotonin, neurotensin, somatostatin, and glutamate. Raphespinal neurons project, in turn, to the dorsal horn and pars caudalis of the trigeminal nucleus. These serotonergic axons terminate on enkaphalinergic interneurons in laminae II and III, which act pre and post-synaptically to suppress the activity of pain transmission. In addition, both the hypothalamus and the PAG project directly to the medullary and spinal cord dorsal horns to act on incoming nociceptive signals. Cholecystokinin and substance P are among the putative neurotransmitters used by PAG projection neurons (Haines 251).
name the three types of opiate receptors, describe their localization and functional significance: ????
in words or by means of a diagram, explain the way in which local dorsal horn circuits modulate afferent nociceptive input: Several transmitter substances are involved in the analgesia system; especially involved are the enkephalins and serotonin. Many of the nerve fibers derived from both periventricular nuclei and the periaqueductal gray area secrete enkephalin at their endings. Thus the endings of many of the fibers in the raphe magnus nucleus release enkephalin. The fibers originating in this nucleus but terminating in the dorsal horns of the spinal cord secrete serotonin at their endings. The serotonin in turn causes local cord neurons to secrete enkephalin. Enkephalin is then believed to cause presynaptic inhibition and postsynaptic inhibition of both incoming type C and type A-delta pain fibers where they synapse in the dorsal horns. It probably achieves the presynaptic inhibition by blocking calcium channels in the membranes of the nerve terminals. Because it is calcium ions that cause release of transmitter at the synapse, such calcium blockage would result in presynaptic inhibition (Guyton 613).
describe the response properties of warmth and cold receptors: The human being can perceive different gradations of cold and heat, progressing from freezing cold to cold to cool to indifferent to warm to hot to burning hot. Thermal gradations are discriminated by at least three types of sensory receptors: the cold receptors, the warmth receptors, and pain receptors. The pain receptors are stimulated only by extreme degrees of heat (<15 and >45 degrees Celsius) or cold and, therefore, are are responsible, along with the cold and warmth receptors, for "freezing cold" and "burning hot" sensations.
Warmth signals (30-49 degrees Celsius) are transmitted mainly over type C nerve fibers (slower transmission rate). On the other hand, cold receptors (10-24 degrees Celsius) are A-delta myelinated nerves (faster). Some cold signals are also transmitted via C fibers (Guyton 619).
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