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Chapter 9: Touch and Pain

9.1 Somatosensory Receptors

  • Types of Somatosensory Receptors
      - Merkel Disks and Meissner's Corpuscles
        - Located in the superficial part of the skin.
        - Involved in the perception of shape and texture.
        - Function in motion detection and grip control.
        - Utilize large myelinated Aβ fibers.
      - Ruffini Endings and Pacinian Corpuscles
        - Found in the deeper parts of the skin.
        - Responsible for sensing skin stretch and vibrations.
        - Also utilize large myelinated Aβ fibers.
      - Free Nerve Endings
        - Spread throughout the skin.
        - Major receptors for pain (nociception).

  • Mechanosensory Receptors
      - Primary touch sensation is detected by mechanosensors that include components such as:
        - Blade-like domain and PIEZO channels in cell membranes.
        - Mechanism: Stretch opens channels in the receptors, leading to the influx of cations.
      - Notable scientist: Dr. Ardem Patapoutian, awarded the Nobel Prize for contributions to understanding PIEZO channels.

  • Receptive Fields and Adaptation
      - Receptor locations and adaptation are categorized as follows:
        - Merkel Disk: Superficial, slow adaptation.
        - Meissner's Corpuscle: Superficial, rapid adaptation.
        - Ruffini Ending: Deep, slow adaptation.
        - Pacinian Corpuscle: Deep, rapid adaptation.

  • Nociceptors and Pain Sensation
      - At an injury site, molecules and mast cells are triggered.
      - Activation leads to:
        - Generation of action potentials (APs) from free nerve endings.
        - Release of Substance P (SP) and Calcitonin Gene-Related Peptide (CGRP).
          - SP: Induces plasma extravasation (causes swelling).
          - CGRP: Induces vasodilation (causes redness and heat).
      - Axonal Reflex: APs travel to axonal branches of the parent axon, contributing to neurogenic inflammation.

  • Heat Sensation via TRP Ion Channels
      - Cold and Heat Sensors: Various temperature-sensitive TRP channels (e.g., TRPM8, TRPV1).
      - Mechanism: Exposure to heat activates TRPV1 channels, leading to signal transmission:
        1. Heat opens ion channels in free nerve endings.
        2. Signal travels via nerves into ascending spinal pathways.

  • Primary Sensory Afferents
      - Sensory neuron cell bodies are located in the dorsal root ganglion.
      - The unipolar neuron splits into:
        - Peripheral branch: connects to sensory receptors.
        - Central branch: projects into the dorsal horn of the spinal cord.

Question 1

Test-like question: In a case study where a patient can feel touch but struggles with fine motor tasks and desensitizes rapidly to touch, analyze where the defect might be located:
  - Possible options include:
    a) Merkel’s disk
    b) Meissner’s corpuscles
    c) Aβ fibers
    d) Ruffini’s endings

9.2 Somatosensation in the Central Nervous System

  • Anatomy of the Spinal Cord
      - Dorsal Horn: Contains somas of sensory interneurons.
      - Dorsal Root: Contains sensory axons.
      - Ventral Root: Contains motor axons (ventral horn).
      - Central Canal: Contains cerebrospinal fluid.

  • Dermatomes: Defined as areas of skin innervated by one segment of the spinal cord.

  • Gate Control Theory
      - Suggests that the dorsal horn projection neurons receive input from Aβ fibers (touch) and C fibers (pain).
        - C fibers excite projection neurons and inhibit inhibitory interneurons, resulting in more pain.
      - Conversely:
        - Activation of Aβ fibers can inhibit projection neurons leading to reduced pain perception.

  • Ascending Touch Pathways (Spinal Cord to Cortex)
      1. Aβ fibers carrying touch and pressure signals enter through the dorsal root and ascend the ipsilateral dorsal column.
      2. They synapse with neurons in the dorsal column nuclei (cuneate and gracile) in the lower medulla (at this point, they remain ipsilateral).
      3. Neurons in the medulla cross midline and ascend via the medial lemniscus to the thalamus.
      4. The medial lemniscus then synapses on the ventral posterior nucleus of the thalamus, projecting to the primary somatosensory cortex (S1).

  • Ascending Pain Pathways (Spinal Cord to Cortex)
      1. Peripheral nociceptors send information through unmyelinated C fibers and small myelinated Aδ fibers to the spinal cord dorsal horn.
      2. Dorsal horn neurons project axons across the midline to the anterior lateral spinal cord forming the anterolateral system.
      3. The ascending axons synapse in the ventroposterior lateral (VPL) nucleus of the thalamus, leading to projections to the primary somatosensory cortex (S1).

  • Pain Versus Touch Pathways
      - Touch pathways ascend primarily ipsilateral.
      - Pain pathways cross to the opposite side at the same spinal level.

  • Other Parts of the Anterolateral System
      - Additional tracts include:
        - Spinoreticular tract (modulating arousal).
        - Spinomesencephalic tract (affective components).
        - Spinohypothalamic tract (to autonomic centers for fight or flight).

  • Primary Somatosensory Cortex: Contains a sensory homunculus map that represents body parts, indicating where sensory information is processed.
      - Projects to:
        - Secondary somatosensory cortex (S2).
        - Posterior parietal cortex (integrates auditory and visual information).
        - Limbic system (linked to emotional responses, especially to pain).

Question 2

Test-like question: A patient presents with loss of sensation in the left hand and left face following an accident. Possible injury locations include:
  - a) Right cervical spine
  - b) Right post-central gyrus
  - c) Left cervical spine
  - d) Left post-central gyrus

9.3 Pain and Itch

  • Pain: Defined as:
      - “An unpleasant sensory and emotional experience associated with, or resembling that associated with actual or potential tissue damage” (Raja et al., 2020).
      - It is a personal subjective experience influenced by biological, psychological, and social factors.
      - Pain can be adaptive or maladaptive, and it can manifest verbally or nonverbally.

  • Categories of Pain:
      - Duration: Acute vs. Chronic.
      - Location and cause:
        - Nociceptive Pain: Direct activation of nociceptors (due to damage/inflammation).
        - Neuropathic Pain: Results from nerve injury, described as burning or electric sensations.

  • Congenital Insensitivity to Pain: Caused by mutation in voltage-gated sodium channel α-subtypes (Nav1.7).

  • Limbic System and Emotional Component
      - Involves areas in temporal and frontal lobes contributing to emotional responses, particularly with pain.
      - Impact of Pain on Mental Health:
        - Chronic pain can lead to depression and vice versa.
        - Treatment of both aspects can improve overall quality of life.

  • Itch Mechanism
      1. Immunogenic proteins from mosquito saliva attract and activate mast cells.
      2. Mast cells secrete histamine:
        - Causes blood vessels to swell and leak, resulting in bumps and redness.
        - Histamine binds to receptors on C and Aδ sensory fibers, leading to itch sensation.

  • Itch Transmission to CNS
      - Involves C-fibers (pruriceptors) and Aδ fibers, not a subclass of pain.

Question 3

Test-like question: Based on the mechanisms of itch and pain, what effect should an anti-histamine have?
  - A) Reduce itch
  - B) Reduce pain
  - C) Reduce itch and pain
  - D) Reduce itch, pain, and thermal sensation.

9.4 Pain Relief

  • Placebo Analgesia:
      - Refers to pain relief from inactive treatments.
      - Effective when associated with previous sensory cues of pain relief or expectation of relief.

  • Non-invasive Pain Relief Methods
      - Over-the-counter drugs, NSAIDs (reduce inflammation), physical therapy, acupuncture.

  • Opioids and Endorphins:
      - Endogenous Opioids: Peptides like beta-endorphin, enkephalins affect pain modulation.
      - Exogenous Opioids: Drugs like morphine act as agonists on μ-opioid receptors, reducing the response to nociceptive activation.
        - Effects:
          - Reduces presynaptic action potential.
          - Suppresses neurotransmitter release.
          - Opens K+ channels in postsynaptic neurons, hyperpolarizing them.

  • Cannabinoids:
      - Both endogenous (anandamide, 2AG) and exogenous (THC) forms that modulate pain signaling in various CNS areas.
        - Mechanism of action involves inhibiting neurotransmitter release.

  • Surgical Treatment Options:
      - Options include decompression, reconstruction, ablation of pain pathways, and modulation of pain signaling.

  • Electric and Magnetic Stimulation Therapies:
      - Techniques like Transcutaneous Electrical Nerve Stimulation (TENS), spinal cord stimulation, and deep brain stimulation have proven effective in chronic pain relief.

  • Transcranial Magnetic Stimulation: Utilizes a magnetic field to alter cortical neuron activity, resulting in potential chronic pain relief.