Pathophysiology of Pain
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Questions and Answers

In the substantia gelatinosa, _____________ is released following the synapse of C fibers with interneurons, which acts to __________ the concentration of substance P.

Endorphins/increase

Which section of the spinal cord is responsible for carrying fast pain and temperature? Which direction does this pathway move?

  • Medial spinothalamic tract/ascending
  • Tract of Lissauer
  • Dorsal column system/ascending
  • Lateral spinothalamic tract/ascending (correct)

    • What is the role of the periventricular & periaqueductal gray in the pain pathway?

    Initiates pathway for pain inhibition and releases both enkelphalin & GABA.

    What are the primary neurotransmitters responsible for the inhibition of pain?

    <ol> <li>Enkephalin, 2. Serotonin.</li> </ol> Signup and view all the answers

    What neurotransmitter is released by the Periaqueductal Gray Matter?

    <p>Enkelphalin &amp; GABA.</p> Signup and view all the answers

    Explain the Intensity Theory of Pain.

    <p>Pain is perceived only if the stimulus is sufficient in intensity and/or frequency. Stimulation of any sensory receptor will cause pain if the stimulus is excessive.</p> Signup and view all the answers

    What is the Gate Control Theory of Pain?

    <p>Sensory signals from primary afferents are modulated by the substantia gelatinosa in the dorsal horn of the spinal cord. Small fibers facilitate the gate, while large fibers inhibit it.</p> Signup and view all the answers

    What is the definition of pain according to the International Association for the Study of Pain?

    <p>Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.</p> Signup and view all the answers

    What is the purpose of pain?

    <p>Protective in nature, withdrawal from heat source, limit damage joint to prevent further injury, leads to learned behaviors such as avoidance which can become dysfunctional.</p> Signup and view all the answers

    Which types of somatic sensory receptors primarily respond to tactile non-painful stimuli? (Select all that apply)

    <p>Meissner’s corpuscles</p> Signup and view all the answers

    ____________ are relatively unspecialized nerve cells that initiate the sensation of pain.

    <p>Nociceptors</p> Signup and view all the answers

    Nociceptors are present only in somatic tissues.

    <p>False</p> Signup and view all the answers

    What is the primary function of the somatosensory system?

    <p>To provide information about touch, proprioception, temperature, pain, and itching</p> Signup and view all the answers

    What type of neurons are responsible for transmitting pain information from the periphery to the spinal cord?

    <p>Sensory neurons</p> Signup and view all the answers

    What is the location of the cell body of first-order neurons?

    <p>In the dorsal root ganglion</p> Signup and view all the answers

    What is primarily responsible for touch, pressure, vibration, and proprioception?

    <p>Dorsal column pathway</p> Signup and view all the answers

    What is the role of withdrawal from a heat source in relation to pain?

    <p>It is a protective mechanism to prevent further tissue damage</p> Signup and view all the answers

    What decussates at the level of the medulla oblongata?

    <p>Dorsal column pathway</p> Signup and view all the answers

    What is the term for the pathways that transmit pain information from the spinal cord to the brain?

    <p>Ascending and descending pathways</p> Signup and view all the answers

    What is released in the substantia gelatinosa following the synapse of C fibers with interneurons?

    <p>Enkephalin</p> Signup and view all the answers

    What is the primary function of pain?

    <p>To protect the body from further tissue damage</p> Signup and view all the answers

    Which tract carries fast pain and temperature?

    <p>Lateral spinothalamic tract</p> Signup and view all the answers

    What is the term for the nerve fibers that transmit fast pain information?

    <p>A-delta fibers</p> Signup and view all the answers

    What is the direction of the lateral spinothalamic tract pathway?

    <p>Ascending</p> Signup and view all the answers

    What is the result of pain leading to learned behaviors?

    <p>Dysfunctional behaviors</p> Signup and view all the answers

    What is primarily responsible for pain and temperature sensations?

    <p>Spinothalamic tract</p> Signup and view all the answers

    How many tracts does the dorsal column pathway have?

    <p>2</p> Signup and view all the answers

    What decussates at the level of the spinal cord?

    <p>Spinothalamic tract</p> Signup and view all the answers

    What is the primary function of thermoreceptors?

    <p>to detect changes in temperature</p> Signup and view all the answers

    Which type of mechanoreceptors responds throughout the duration of the stimulus?

    <p>Merkel's disks and Ruffini's corpuscles</p> Signup and view all the answers

    What is the primary function of nociceptors?

    <p>to initiate the sensation of pain</p> Signup and view all the answers

    Which type of somatic sensory receptors are present in both somatic and visceral tissues?

    <p>Nociceptors</p> Signup and view all the answers

    What type of fibers are associated with the transmission of fast pain?

    <p>A-delta fibers</p> Signup and view all the answers

    Which type of receptors are responsible for sensing temps between 30-45°C?

    <p>Warm receptors</p> Signup and view all the answers

    What type of receptors respond to continuous heavy touch and pressure?

    <p>Ruffini's corpuscles</p> Signup and view all the answers

    Which type of mechanoreceptors are rapidly adapting and respond at the onset/offset of the stimulus?

    <p>Meissner's corpuscles and Pacinian corpuscles</p> Signup and view all the answers

    Which pathway carries sensory information from the face, head, mouth, and nasal cavity?

    <p>Trigeminal Pathway</p> Signup and view all the answers

    What is the function of the Fasciculus gracilis?

    <p>Carries sensory information from the lower body</p> Signup and view all the answers

    What is the function of the Spinoreticular tract?

    <p>Mediates arousal and autonomic responses to pain</p> Signup and view all the answers

    Where do the axons of the Dorsal Column Pathway terminate?

    <p>Thalamus</p> Signup and view all the answers

    What is the function of the Fasciculus cuneatus?

    <p>Carries sensory information from the upper body</p> Signup and view all the answers

    What is the function of the Spinohypothalmic tract?

    <p>Evoke emotional behavior</p> Signup and view all the answers

    What is the function of the Medial Lemniscus?

    <p>Ascends the brainstem as a bundle of axons from the Dorsal Column Pathway</p> Signup and view all the answers

    What type of second-order neurons stretch from the medulla to the thalamus?

    <p>Dorsal column-medial lemniscal pathway neurons</p> Signup and view all the answers

    According to the Gate Control Theory of Pain, which type of fibers facilitate the transmission of sensory information?

    <p>Small fibers</p> Signup and view all the answers

    What is the proposed location of the 'gate' in the spinal cord according to the Gate Control Theory of Pain?

    <p>Substantia gelatinosa in the dorsal horn</p> Signup and view all the answers

    What is a limitation of the Gate Control Theory of Pain?

    <p>It is based on flawed concepts of neural architecture</p> Signup and view all the answers

    What is a characteristic of pain according to Melzack and Casey's 1968 theory?

    <p>It is a multidimensional and complex experience</p> Signup and view all the answers

    What is a recent finding about pain, discovered in 2011?

    <p>The peripheral encoding of nociceptive stimuli differs from CNS processing and perception of pain</p> Signup and view all the answers

    According to the Gate Control Theory, which type of fibers inhibit the transmission of sensory information?

    <p>Large fibers</p> Signup and view all the answers

    What is a common feature of pain theories, including the Gate Control Theory?

    <p>They are all too simplistic</p> Signup and view all the answers

    Which aspect of pain is highlighted by the Gate Control Theory?

    <p>Modulation of sensory information transmission</p> Signup and view all the answers

    Study Notes

    Definition of Pain

    • Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage.
    • Most common symptom that brings patients to see a physician.

    Purpose of Pain

    • Protective in nature: withdrawal from heat source, limit damage to joints to prevent further injury.
    • Leads to learned behaviors: avoidance, behaviors can become dysfunctional.

    Anatomy of Pain

    • The somatosensory system provides information about: touch, proprioception, temperature, pain, and itching.
    • The somatosensory system consists of:
      • Peripheral nervous system
      • Spinal cord
      • Brain (somatosensory cortex, thalamus)

    First-Order Neurons

    • Cell body located in the dorsal root ganglion and lies in the vertebral foramina at each spinal cord level.
    • Each neuron has a single axon that bifurcates:
      • One end travels distal to the periphery.
      • The other end travels into the dorsal horn of the spinal cord.

    Axons

    • The neuronal process that carries the action potential from the nerve cell body to a target.
    • In the somatosensory system, primarily concerned with 3 fibers:
      • A-beta fibers
      • A-delta fibers
      • C fibers
    • May or may not be myelinated, which impacts the speed of signal transmission.

    Somatic Sensory Receptors

    • Diverse in composition:
      • Free nerve endings in the skin
      • Specialized nerve endings (act as amplifiers or filters)
      • Sensory terminals associated with specialized transducing cells
    • All somatic sensory receptors fundamentally work the same way:
      • Stimuli applied to the skin deform or otherwise change the nerve ending, which affects the ionic permeability of the receptor membrane.
      • The resulting change in permeability generates a depolarizing current, thereby triggering action potentials.

    Mechanoreceptors

    • Respond to tactile non-painful stimuli.
    • Provide information regarding:
      • Touch
      • Pressure
      • Vibration
      • Tickle
      • Position senses (static position and rate of movement)
    • Divided into two functional groups based on their response during stimulation:
      • Rapidly adapting
      • Slowly adapting
    • Four major types of mechanoreceptors:
      • Meissner's corpuscles
      • Pacinian corpuscles
      • Merkel's disks
      • Ruffini's corpuscles

    Thermoreceptors

    • Function to detect changes in temperature using two types of receptor cells:
      • Warm: sense temperatures between 30-45°C
      • Cold: sense temperatures between 17-27°C
    • Poor indicators of absolute temperature.
    • Sense of temperature comes from the comparison of signals from the two types of receptors.

    Nociceptors

    • Relatively unspecialized nerve cells with "free endings" that initiate the sensation of pain.
    • Conduction along the axons is relatively slow compared to that of mechanoreceptors.
    • Split into two pathways:
      • Fast pain: A-delta fibers
      • Slow pain: C fibers

    Spinal Cord Anatomy

    • Gray matter:
      • Dorsal horn (sensory)
      • Ventral horn (motor)
      • Lateral (autonomic)
    • White matter
    • Central canal

    Rexed's Laminae

    • Lamina I:
      • Marginal layer
      • Receives noxious stimuli from cutaneous and deep somatic tissues via both A-delta and C fibers
      • Relays pain, temperature
    • Lamina II:
      • Substantia gelatinosa of Rolando
      • Receives noxious stimuli from C fibers and A-delta fibers to a lesser degree
      • Relays pain, temperature, and mechanical (light touch) information
      • Considered major site of action for opioids
    • Lamina III/IV:
      • Nucleus proprius
      • Receives input from A-beta and A-delta fibers
      • Relays proprioception, mechanical, pain, and temperature sensations
      • First synapse in the spinothalamic tracts occur here

    Ascending Pathways

    • Dorsal column pathway:
      • Carries sensory information from the body
      • Axons enter the spinal cord and travel ipsilaterally
      • Decussate at the level of the medulla
      • Axons terminate in the thalamus
    • Spinothalamic pathway:
      • Carries sensory information from the body
      • Axons enter the spinal cord and travel contralaterally
      • Decussate at the level of the spinal cord
      • Axons terminate in the thalamus

    Neurotransmitters

    • Pain initiators:
      • Glutamate
      • Substance P
      • Calcitonin gene-related peptide
      • Asparate
      • Bradykinin
      • Prostaglandins
    • Pain inhibitors:
      • GABA
      • Serotonin
      • Endorphins
      • Enkephalins
      • Dynorphin
      • Glycine
      • Adenosine
      • Norepinephrine
      • Acetylcholine
      • ATP### Third-Order Neurons
    • Cell body located in the thalamic relay nuclei
    • Axons synapse in the thalamus with second-order neurons (specifically in the ventro-posterior thalamus)
    • Axons terminate on the somatosensory cortex (Area I in the postcentral gyrus of the parietal cortex and Area II in the superior wall of the Sylvian fissure)
    • Send fibers to areas of the postcentral gyrus of the parietal cortex and superior wall of the Sylvian fissure

    Somatosensory Cortex

    • Receives sensory aspects of pain
    • Interacts with anterior cingulate cortex, which is associated with emotional distress related to pain
    • Linked to limbic cortex and insular cortex, which are associated with emotion and addiction

    Descending Pain Pathway

    • Responsible for pain inhibition
    • Descending neurons originate in the periventricular and periaqueductal gray
    • Transmit through the nucleus raphe magnus to the substantia gelatinosa via the descending dorsolateral funiculus
    • Upon reaching Rexed's lamina II, synapse with interneurons

    Periaqueductal Gray Matter

    • Located around the cerebral aqueduct within the tegmentum of the midbrain
    • Initiates pathway for pain inhibition
    • Releases both enkephalin and GABA

    Nucleus Raphe Magnus

    • Thin midline nucleus located in the pons and upper medulla
    • Transmits second-order signals via the dorsolateral columns in the spinal cord to the dorsal horns of the spinal cord
    • Releases 5-HT (serotonin) which descends to the dorsal horn of the spinal cord and forms excitatory connections with inhibitory interneurons located in lamina II

    Key Inhibitory Neurotransmitters

    • Enkephalin: released by periaqueductal gray matter, inhibits pain
    • Serotonin: released by nucleus raphe magnus, inhibits pain
    • GABA: released by periaqueductal gray matter, inhibits pain

    Pain Pathways

    • Dorsal column system: responsible for transmission of sensory information from mechanoreceptors, thermoreceptors, and nociceptors
    • Descending pain pathway: responsible for pain inhibition
    • Ascending pain pathway: transmits pain information from the spinal cord to the thalamus and somatosensory cortex

    Theories of Pain

    • Descartes' Theory of Pain: describes pain as a perception that exists in the brain and makes a distinction between the neural phenomenon of sensory transduction and the perceptual experience of pain
    • Specificity Theory of Pain: proposes that each modality has a specific receptor and associated sensory fiber that is sensitive to one specific stimulus
    • Intensity Theory of Pain: defines pain as an emotion that occurs when a stimulus is stronger than usual
    • Pattern Theory of Pain: proposes that sensory impulses are coded according to the number of receptors stimulated and the rate of their discharge
    • Gate Control Theory of Pain: proposes that the "gate" in the spinal cord is the substantia gelatinosa, which modulates the transmission of sensory information from primary afferent neurons to transmission cells in the spinal cord

    Mechanoreceptors

    • Divided into two functional groups: rapidly adapting (respond at the onset/offset of the stimulus) and slow adapting (respond throughout the duration of the stimulus)
    • Four major types: Meissner's corpuscles (rapidly adapting), Pacinian corpuscles (rapidly adapting), Merkel's disks (slow adapting), and Ruffini's corpuscles (slow adapting)

    Thermoreceptors

    • Function to detect changes in temperature using two types of receptor cells: warm (sense temps between 30-45°C) and cold (sense temps between 17-27°C)
    • Poor indicators of absolute temperature, sense of temperature comes from the comparison of signals from the two types of receptors

    Nociceptors

    • Relatively unspecialized nerve cells with "free endings" that initiate the sensation of pain
    • Conduction along the axons is relatively slow compared to that of mechanoreceptors
    • Split into two pathways: fast pain (A-delta fibers) and slow pain (C fibers)
    • Present in both somatic and visceral tissues, with three major classes: A-delta mechanosensitive nociceptors, A-delta mechanothermal nociceptors, and polymodal nociceptors

    Somatic Sensory Receptors

    • Receptor type, location, function, and associated axon:
      • Meissner's corpuscles: glabrous skin, touch and vibration, A-beta fibers
      • Pacinian corpuscles: subcutaneous tissue, interosseous membranes, and viscera, vibration, A-beta fibers
      • Merkel's disks: all skin, hair follicles, continuous touch, A-beta fibers
      • Ruffini's corpuscles: all skin, continuous heavy touch and pressure, A-beta fibers
      • Thermoreceptors: skin, temperature, A-delta fibers (cold receptors) and C fibers (warmth receptors)
      • Free nerve endings: skin, organs, pain, itch, touch, and pressure, A-delta fibers and C fibers

    Definition of Pain

    • International Association for the Study of Pain: an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage
    • Most common symptom that brings patients to see a physician

    Purpose of Pain

    • Protective in nature, leading to withdrawal from heat sources and limiting damage to joints to prevent further injury
    • Leads to learned behaviors, including avoidance and dysfunctional behaviors

    Anatomy of Pain

    • The somatic senses are the nervous mechanisms that collect sensory information from all over the body
    • The somatosensory system provides information about touch, proprioception, temperature, pain, and itching
    • The somatosensory system consists of the peripheral nervous system, spinal cord, and brain
    • Afferent neurons and A-delta and C fibers are involved in the transmission of pain signals

    First-Order Neurons

    • Cell body located in the dorsal root ganglion and lies in the vertebral foramina at each spinal cord level
    • Each neuron has a single axon that bifurcates, with one end traveling distal to the periphery and the other end traveling into the dorsal horn of the spinal cord

    Axons

    • The neuronal process that carries the action potential from the nerve cell body to a target
    • Fasciculus gracilis (axons from lower body/legs) and fasciculus cuneatus (axons from upper body/arms) are involved in the transmission of pain signals

    Dorsal Column Pathway

    • First-order axons in the dorsal column rapidly travel ipsilaterally and terminate in the medulla where they synapse with second-order neurons
    • Axons in this pathway mediate sensation and proprioception
    • Axons decussate the midline of the medulla and ascend the brainstem as a bundle called the medial lemniscus
    • Second-order neurons terminate in the thalamus and synapse with a third-order neuron

    Trigeminal Pathway

    • Carries sensory information from the face, head, mouth, and nasal cavity
    • Axons enter the brain stem at the level of the pons or the mesencephalic nuclei in the midbrain
    • Axons carry information similar to that of the dorsal column pathway (touch/pressure/vibration/proprioception)

    Alternative Pain Pathways

    • Spinoreticular tract: mediates arousal and autonomic responses to pain
    • Spinomesencephalic tract: may activate antinociceptive pathways
    • Spinohypothalmic and spinotelencephalic tracts: evoke emotional behavior
    • Spinocervical tract: alternative pathway for pain
    • Fibers in the dorsal columns: responsible for light touch and proprioception

    Second-Order Neurons

    • Cell body location varies based on ascending pathway
    • Location that the axon decussates is dependent upon the ascending pathway the particular neuron is located in
    • Two types of second-order neurons: wide dynamic range and narrow dynamic range
    • Wide dynamic range neurons are primarily responsible for touch, pressure, vibration, and proprioception
    • Narrow dynamic range neurons are primarily responsible for pain and temperature sensations

    Gate Control Theory of Pain

    • Proposed that the "gate" in the spinal cord is the substantia gelatinosa in the dorsal horn
    • The gating mechanism is controlled by the activity of the large and small fibers
    • Small fibers (pain sensations) facilitate/open the gate
    • Large fibers (non-pain sensations) inhibit/close the gate

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    Description

    Definition and purpose of pain, international association for the study of pain, and its symptoms. Learn about the protective nature of pain and how it brings patients to see a physician.

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