22/23

Somatosensation

• Definition:

  • A diverse sensory system associated with afferent neurons in the skin, muscles, and joints.

  • Concerned with the perception of touch, pressure, movement, and vibration (to be discussed on Monday).

  • Focused on cutaneous mechanoreceptors that yield information about external stimuli (exteroception).

• Topics to Cover:

  • Pain and temperature (Friday/next Monday).

  • Position and movement (Wednesday,Today).

• Types of Sensation:

  • Interoception: Mechanical forces arising from inside the body.

  • Proprioception: The ability to sense the position of our limbs and body parts in space.

  • Kinesthesia: The sense of movement.

    • Information comes from specialized receptors in muscles, tendons, and joints.

• Pain and Temperature:

  • Pain: An unpleasant sensory and emotional experience associated with stimuli that cause real or potential tissue damage.

  • Nociception:

    • The perception of injurious stimuli; specialized receptors detect both internal and external stimuli.

Nociceptors

• Definition:

  • Specialized nerve cells that innervate skin, tissues, and internal organs to initiate the sensation of pain.

  • React to various stimuli: mechanical, chemical, and thermal.

  • Pseudounipolar Neurons:

    • Have one branch projecting peripherally and the other to either the dorsal column (DC) of the spinal cord or the trigeminal ganglia.

  • Peripheral Axons:

    • Terminate in free nerve endings.

    • Can be either unmyelinated or lightly myelinated.

• Types of Axons:

  • Aγ fibers: Lightly myelinated fibers involved in transmitting fast, sharp pain.

  • C fibers: Unmyelinated fibers that transmit slower, dull pain.

  • Aβ fibers: Heavily myelinated fibers (very small minority) stimulate and generate pain sensations.

Different Types of Pain

• First Pain:

  • Transmission:

    • Via Aγ nociceptor fibers (faster conducting).

  • Characteristics:

    • Sharp, prickling sensation.

  • Types:

    • Type I: Responds to intense mechanical and chemical stimuli; high heat threshold.

    • Type II: Responds to high mechanical stimulation and low heat threshold.

    • Specialized systems for transmission of mechanical or heat nociception.

• Second Pain:

  • Transmission:

    • Via C nociceptor fibers (slower conducting).

  • Characteristics:

    • Duller, diffuse, and long-lasting pain sensation.

  • Polymodal Pain:

    • Responds to all nociceptive stimuli (mechanical, chemical, thermal) and demonstrates subsets based on receptor/channel expression that show preferential stimulus responses.

Transient Receptor Potential (TRP) Channels

• Definition:

  • Cation channels (e.g., Na+ and Ca2+) involved in sensory transduction.

  • Temperature-gated, but some also respond to mechanical or chemical stimuli.

  • Threshold for hot thermal noxious stimulus:

    • TRPV4: Mechanically gated.

    • TRPA1: Chemically gated.

TRPV1 Channel

• Characteristics:

  • Expressed in both Aγ and C fibers.

  • Responds to high temperatures (from 43ºC) and capsaicin (the spicy component in peppers).

• Effects:

  • Produces a tingling or burning sensation associated with spicy foods.

• Pain Relief:

  • Repeated application can desensitize pain fibers and decrease the release of neuromodulators.

  • Used topically as a pain reliever for conditions like arthritis and neuralgias.

  • Interesting Fact: Found in all mammals but not in birds (squirrel-proof birdseed).

TRP Channels and Cold Noxious Sensation

• Involvement:

  • Both Aγ and C fibers are involved in cold sensation.

  • Approximately 10-20% of somatosensory afferent cell bodies in the dorsal root ganglia (DRG)/trigeminal ganglia process cold signals.

  • Most are sensitive to menthol, which provides pleasant cooling effects.

  • Key TRP Channel:

    • TRPM8 Threshold: Specifically responsive to cold thermal noxious stimuli.

Somatosensation Processing

• Body:

  • Mechanosensory information is processed in the dorsal column/medial lemniscal (DC/ML) pathway.

  • Pain and temperature sensation are processed via the anterolateral system.

• Face:

  • Mechanosensation and pain/temperature are processed through the trigeminal system.

Anterolateral System (AL)

• Neural Pathways:

  • Nociceptors have their cell bodies located in the DRG.

  • They enter the spinal cord and their collateral branches can ascend/descend 1-2 levels, forming Lissauer's tract.

  • They synapse onto second-order neurons in the dorsal column (DC) in a lamina-specific manner:

    • Aγ fibers: Synapse in Lamina 1 and 5.

    • C fibers: Synapse primarily in Lamina 1/2 and some in Lamina 5.

  • They decussate and ascend in the anterolateral tract towards the brainstem and thalamus.

Referred Pain

• Concept:

  • Wide Dynamic Range Neurons:

    • Multimodal Lamina 5 neurons that receive converging inputs from both nociceptive (pain) and non-nociceptive (non-pain) inputs, including visceral sensory inputs.

    • Contribute to referred pain—pain perceived in a somatic location due to visceral organ damage.

    • Example: Angina, where heart pain is felt in the arm or back.

Effects of Decussation on Loss of Function

• Dorsal Column/Medial Lemniscal Pathway (DC/ML):

  • Cutaneous sensation is affected from the neck down.

  • Decussates in the brainstem, resulting in ipsilateral loss of sensation.

• Anterolateral System:

  • Pain and temperature sensation affects the neck down.

  • Decussates in the spinal cord, resulting in contralateral loss of sensation.

  • Dissociated Sensory Loss: Loss of mechanosensation on one side and loss of pain and temperature sensation on the other side, e.g., seen in Brown-Sequard Syndrome.

Pain Matrix

• Components:

  • Sensory-Discriminative Aspects of Pain:

    • Involve location, intensity, and quality of the stimulus.

  • Affective-Motivational Aspects of Pain:

    • Includes unpleasant feelings, fear, anxiety, and autonomic activation (e.g., fight-or-flight responses).

  • Collectively referred to as the pain matrix, engaging limbic structures.

Pain and Temperature for Head and Face

• Nociceptors:

  • Have cell bodies in the trigeminal ganglia, as well as associated ganglia from facial, glossopharyngeal, and vagal cranial nerves.

  • Enter the pons and descend to the medulla via the spinal trigeminal tract.

  • Terminate in two subdivisions of the trigeminal nucleus.

  • Decussate and ascend in the trigemino-thalamic tract to the VPM thalamus and primary sensory cortex (SI).

  • Involved in both sensory-discriminative and affective-motivational characteristics of pain processing.

Importance of AL Tract for Non-Noxious Stimuli Somatosensation

• Functions:

  • Critical for nociception, but also mediates non-discriminative touch (tactile stimulation that lacks fine spatial resolution) and innocuous temperature sensation.

  • Distinguishes warm and cold sensations, which have distinct afferents that are separate from noxious heat (>43ºC) and cold (<15ºC).

  • Itching:

    • Mediated by pruriceptors (e.g., histamine receptors).

Pain Sensitivity

• Hyperalgesia:

  • Increased perception of pain that occurs in damaged tissue and surrounding areas.

  • Results from changes in neuronal sensitivity at both the peripheral and central levels.

  • Example: Increased sensitivity to pain following a sunburn.

• Allodynia:

  • Where non-painful stimuli evoke severe pain.

  • Also due to changes in neuronal sensitivity at both the peripheral and central levels.

  • Not a disease or disorder, but a symptom.

  • Example: Nerve damage may cause allodynia.

• Mechanisms:

  • Both hyperalgesia and allodynia can occur due to changes at the peripheral and central level.

    • Peripheral Sensitization: Involves an increased responsiveness of nociceptive afferents post tissue damage.

    • Central Sensitization: Refers to heightened excitability in central pathways post-injury.

Peripheral Sensitization

• Definition:

  • Increases the responsiveness of nociceptive afferents after tissue damage.

• Mechanisms:

  • Interaction between nociceptors and released “inflammatory soup” post-tissue damage.

    • Tissue Damage:

    • Nociceptors release substances like Substance P and CGRP that potentiate inflammation, causing vasodilation, swelling, and histamine release.

    • Non-neuronal cells contribute by releasing pro-inflammatory factors (e.g., histamine from mast cells, pro-inflammatory chemicals from macrophages).

    • These interactions aim to protect the injured site and promote healing while guarding against infection.

Pharmacological Interventions

• NSAIDs (e.g., aspirin, ibuprofen):

  • Work by decreasing COX, an enzyme necessary for prostaglandin production.

• TNF-α Blockers:

  • Used to treat autoimmune disorders (e.g., Crohn’s disease).

• NGF Blockers:

  • Reduce hyperalgesia in rodent models.

  • CGRP may enhance nociceptor conduction by increasing Na+ currents, resulting in nociceptor activation.