AE

Nociceptor Activation, Sensory Pathways, and Pain Modulation

  • Nociceptor Activation and Pain Threshold

    • Nociceptors (pain receptors) begin to fire action potentials at roughly 43 ext{ Celsius } (109.4 ext{ Fahrenheit}).
    • When activated, these receptors allow sodium ( ext{Na}^+) to flow across the cell membrane, causing the membrane potential to change and depolarize.

  • Sensory Pathways to the Somatosensory Cortex

    • The body uses different pathways for transmitting information related to touch and proprioception versus pain and temperature.
    • A key distinction between these pathways is where and when the neurons cross over (decussate) in the central nervous system.

  • Pathway for Pain and Temperature (Anterolateral System / Spinothalamic Tract)

    • First-order neuron: The cell body is located in the dorsal root ganglion.
      • These neurons enter the spinal cord via the Tract of Lissauer.
      • They immediately have axon terminals that synapse in various layers (1 ext{ to } 5) of the dorsal horn of the spinal cord (this is where the first synapse occurs).
    • Second-order neuron: These neurons cross over to the contralateral side within the spinal cord itself (at or near the level of entry).
      • They then ascend to the brain via the anterolateral system, also known as the spinothalamic tract.
      • These neurons synapse in the Ventral Posterior Lateral (VPL) or Ventral Posterior Medial (VPM) nuclei of the thalamus.
    • Third-order neuron: Projects from the thalamus to the somatosensory cortex.

  • Pathway for Touch and Proprioception (Dorsal Column-Medial Lemniscus Pathway)

    • First-order neuron: The cell body is located in the dorsal root ganglion.
      • These neurons enter the spinal cord and ascend ipsilaterally (on the same side) in the dorsal column.
      • They travel up to the brainstem and synapse in the gracile and cuneate nuclei located in the medulla.
    • Second-order neuron: These neurons cross over to the contralateral side in the medulla, forming the medial lemniscus.
      • They then ascend contralaterally (on the opposite side) through the brainstem.
      • These neurons synapse in the Ventral Posterior Lateral (VPL) or Ventral Posterior Medial (VPM) nuclei of the thalamus.
    • Third-order neuron: Projects from the thalamus to the somatosensory cortex.
    • This pathway transmits information about discriminative touch, vibration, and proprioception.

  • Dissociated Sensory Loss (Clinical Application)

    • Understanding the distinct decussation points of these pathways is crucial for diagnosing and understanding patterns of sensory loss resulting from spinal cord lesions (e.g., Brown-Séquard syndrome).
    • At the site of the lesion: There will be a complete loss of all sensation due to the damage affecting all incoming afferent fibers at that spinal segment.
    • Ipsilateral to the lesion (same side of the body) and below the lesion: Loss of touch, vibration, and proprioception occurs because the dorsal column (which carries this information and ascends ipsilaterally) is damaged.
    • Contralateral to the lesion (opposite side of the body) and below the lesion: Loss of pain and temperature sensation occurs because the spinothalamic tract (which carries this information and has already crossed over in the spinal cord) is damaged.
    • This scenario results in sensory deficits on both sides of the body below the lesion, but with different types of sensation affected on each side.

  • Visceral and Referred Pain

    • Referred pain is a phenomenon where pain originating from internal organs (visceral pain) is perceived as coming from a somatic part of the body (e.g., skin, muscle).
    • This happens due to the convergence of afferent neurons from visceral organs and afferent neurons from somatic regions onto the same second-order neurons in the spinal cord's dorsal horn.
    • The brain, accustomed to interpreting signals from somatic regions, misinterprets the visceral pain signal as originating from the more commonly stimulated somatic area.

  • Clinical Intervention for Chronic Pain: Midline Myelotomy

    • This surgical procedure can be performed to alleviate intense, chronic internal pain, particularly in patients with conditions like cancer.
    • It aims to block painful information by lesioning specific pathways in the spinal cord.
    • A midline myelotomy primarily targets and blocks painful information transmitted by the anterolateral system (spinothalamic tract) as it sends signals to the somatosensory cortex through the VPL or VPM of the thalamus.

  • Pain Modulation

    • The perception of pain is not merely a direct relay of signals; it is actively modulated by the brain.
    • The nervous system includes descending pathways from the brain that can actively suppress or enhance pain signals.

  • Peripheral Sensitization

    • Refers to changes in the responsiveness of nociceptors (pain receptors) after an injury.
    • Mechanism: An injury triggers an inflammatory response, leading to the release of various substances at the injury site, collectively termed the "inflammatory soup." These substances include prostaglandin, ATP, 5 ext{HT} (serotonin), and others.
    • These substances:
      • Can directly activate or increase the activity of pain receptors, such as the TRPV1 receptor.
      • Can reduce the threshold at which nociceptors fire action potentials, making them more sensitive to stimuli that were previously non-painful or mildly painful.
    • This sensitization typically subsides as the injury heals.

  • Central Sensitization

    • Involves changes in the excitability and processing capabilities of neurons within the spinal cord itself.
    • Neurons in the spinal cord become sensitized, exhibiting:
      • Increased excitability.
      • Reduced inhibition.
      • Expanded receptive fields (responding to stimuli from a wider body area).
    • Like peripheral sensitization, it often resolves with healing, but persistent central sensitization can contribute to chronic pain states.

  • Phantom Limb Pain

    • This is an example of maladaptive plasticity within the nervous system.
    • After an amputation, a patient may still experience the sensation, often painful, of their missing limb.
    • This phenomenon reflects complex reorganizational changes in the somatosensory cortex and related brain areas following the loss of a limb.

  • Descending Pain Suppression Systems

    • The brain possesses robust mechanisms to actively suppress the perception of pain.
    • These involve descending pathways that originate from higher brain centers and project down to the spinal cord, where they can inhibit the transmission of pain signals (as indicated by