Mechanosensation and Pain

Mechanosensation

Touch:

Stimulus → mechanoreceptor → transduction → Aβ fiber (1st order neuron)→ dorsal column-medial lemniscus → medulla (2nd order neuron) → thalamus (3rd order neuron) → somatosensory cortex

• Mechanoreceptors can be rapidly or slowly adapting

Mechanosensory stimuli are transduced by specific receptors:

Different forms are sensitive to pressure, stretch, vibration, acceleration, and sound

Five types of touch receptors in the skin:

• Pacinian corpuscle

• Meissner’s corpuscle

• Merkel’s disc

• Ruffini’s ending

• Free nerve ending

Free Nerve Endings

Various touch and pressure; pain

Merkel’s Disc

• Steady pressure; texture

• Small, sharp borders

• Slow-adapting

Meissner’s Corpuscle

• Stroking, flutter

• Small, sharp borders

• Fast-adapting

Pacinian/Lamellated Corpuscle

• Vibration; changes in pressure

• Large, vague borders

• Fast-adapting

Ruffini’s Ending

• Stretch

• Large, vague borders

• Slow-adapting

Pacinian Corpuscle: Transduction Mechanism

1. Mechanical stimulus deforms the corpuscle

2. Membrane deformation opens mechanosensitive channels (PIEZO2)

3. A graded depolarization is produced

4. If threshold is reached, and action potential is generated in the A-beta fiber

Fine Touch and Proprioception: Dorsal Column – Medial Lemniscus Pathway

1. Touch receptors detect stimulation of the skin and send action potentials along axons that enter dorsal roots of the spinal cord. This axon is part of a unipolar neuron, the cell body of which resides in the dorsal root ganglion.

2. Once the axon enters the spinal cord dorsal horn, it joins the dorsal column of white matter and ascends to the brain.

3. In the medulla, the axon from the periphery makes its first synapse, innervating a neuron of the dorsal column nuclei. This medullary neuron in turn sends its axon across the midline and up to the thalamus.

4. At this point, the left thalamus will be receiving information about the right side of the body. The thalamus will in turn send this information to the somatosensory cortex.

Pain

• An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage (the International Association for the Study of Pain)

• Primarily a protective mechanism meant to bring a conscious awareness that tissue damage is occurring or is about to occur

• Storage of painful experiences in memory helps us avoid potentially harmful events in future

• Noxious stimulus → nociceptor → Aδ/C (1st order neuron) → dorsal horn (2nd order neuron) → spinothalamic tract → thalamus (3rd order neuron) → somatosensory cortex

Congenital Analgesia

an extremely rare genetic disorder that prevents a person from feeling physical pain from birth

Stimulation of Nociceptors Produces the Perception of Pain

• Nociceptors are generally free nerve endings

• There are three categories of pain receptors:

  • mechanical receptors respond to mechanical damage (cutting, crushing, pinching)

  • thermal receptors respond to temperature extremes

  • polymodal nociceptors respond to damaging stimuli

• Nociceptors show little/no adaptation to sustained noxious stimulation

• They can be sensitized

Nociceptor Signal Transduction

1. Noxious stimulus (mechanical, thermal, or chemical)

2. Activation of nociceptor ion channels

• Noxious stimuli open nonselective cation channels (e.g., TRPV1, TRPA1, ASIC)

3. Generation of action potentials

• If the generator potential reaches threshold, voltage-gated Na+ channels open and action potentials are generated

4. Dorsal root ganglion:

• The cell body is in the dorsal root ganglion

5. Synaptic transmission in spinal cord

• Action potentials trigger NT release (e.g., glutamate, substance P) onto dorsal horn neurons

A-beta Fibres

• Large diameter, heavily myelinated, very fast conduction (30-70 m/s)

• Light touch, proprioception

• Non-painful touch

A-delta Fibres

• Small diameter, thinly myelinated, fast conduction (5-30 m/s)

• noxious mechanical/chemical

• Fast pain (first pain) → sharp and well localized

C Fibres

• Small diameter, unmyelinated, slow conduction (0.5-2 m/s)

• Noxious mechanical/chemical

• Slow pain (second pain) → dull, burning, poorly localized, long-lasting

Nociceptive Transmission in the Dorsal Horn

1. A-delta and C fibres enter the dorsal horn and form synapses with second-order neurons

2. Primary nociceptive afferents release:

• Glutamate: major fast excitatory NT (acts on AMPA receptors)

• Substance P: contributes to prolonged nociceptive signalling

3. Second-order neurons then project to higher brain regions via ascending pain pathways (e.g., spinothalamic tract)

Pain Ascending System: Pain Perception: Spinothalamic Pathway

1. Pain information is carried by rapidly conducting myelinated A-delta fibres and slowly conducting unmyelinated C fibres

2. Axons of dorsal horn neurons cross the midline and ascend to the spinal cord in the anterolateral quadrant

3. Pain information is provided to various brainstem sites, which control pain-related behaviour such as vocalization

4. Pain information is distributed to many thalamic and cortical areas

5. Cingulate cortex is especially activated by pain information

Brown-Séquard Syndrome

A rare incomplete spinal cord injury caused by damage to one lateral half of the spinal cord:

• Segmental loss of pain and temperature (ipsilateral at level of lesion)

• Loss of pain and temperature (contralateral, below lesion)

• Loss of fine touch, vibration, and proprioception (ipsilateral, below lesion)

Chronic Pain and Pain Sensitization

• Chronic pain may persist after an injury or occur without ongoing tissue damage

• Pain pathways can become sensitized → increased responsiveness to sensory input

• Sensitization can occur at both peripheral and central levels

Hyperalgesia

an increased pain response to a stimulus that is normally painful (primary and secondary)

Allodynia

• Pain produced by a stimulus that is normally non-painful

• Normally innocuous (non-painful) touch input gains access to nociceptive circuits, often due to loss of inhibitory control and/or abnormal synaptic connectivity in the dorsal horn

• Often A-beta touch fibres

Peripheral Sensitization

• Increase sensitivity of nociceptors at the site of injury

• A-delta and C fibres

• Lowered threshold, increased excitability

• Tissue injury releases inflammatory mediators (e.g., prostaglandins, bradykinin, histamine, cytokines)

• These mediators act on nociceptor receptors/ion channels (e.g., TRPV1, ASIC, TRPA1)

• Lower activation threshold and increased excitability

• Result: greater input from the periphery

• Contribute to primary hyperalgesia

Central Sensitization

• Increased excitability of neurons in the dorsal horn

• A-delta (± C) fibres

• Glutamate activates AMPA and NMDA receptors, increasing Ca2+ entry and neuronal excitability

• Substance P activates NK1 receptors, producing slower, longer-lasting excitation

• Increased excitability and synaptic strengthening in dorsal horn neurons

• Result: amplified pain signalling within CNS

• Contribute to secondary hyperalgesia and allodynia

Descending Pain Modulation: Endogenous Analgesia

1. The periaqueductal gray (PAG) activates descending inhibitory pathways (endogenous opioids) to the spinal dorsal horn

2. Endogenous opioids act on opioid receptors at presynaptic nociceptive terminals and postsynaptic dorsal-horn neurons

3. These actions reduce NT release and neuronal excitability, resulting in less pain signal transmission (analgesia)

Why does rubbing an injury reduce pain?

Gate control theory of pain modulation:

• Rubbing activates A-beta touch fibres, which recruit inhibitory interneurons in the dorsal horn, reducing the transmission of nociceptive signals to the brain

• Pain input only → “gate open”

  • Pain input to brain (strong)

• Pain input + touch → “gate partially closed”

  • Pain signal to brain (reduced)

  • Inhibitory interneuron (GABA/glycine)

You stopped noticing your clothes:

Many touch receptors adapt to constant stimulation, allowing the nervous system to emphasize change rather than everything touching you continuously.

You have tiny “onions” under your skin:

Pacinian corpuscles have concentric layers and are especially good at detecting vibration and changes in pressure.

One injury can hurt twice:

Fast, thinly myelinated Aδ fibers give you the sharp first pain; slower unmyelinated C fibers produce the delayed burning/aching second pain.

Touch and pain cross at different places:

Fine touch crosses in the medulla, while pain crosses in the spinal cord - which explains the characteristic sensory pattern in Brown-Séquard syndrome.

Your pain system can turn up its own volume:

Peripheral and central sensitization can make painful stimuli hurt more (hyperalgesia) or make normally harmless touch painful (allodynia)

Your brain has its own pain-control system:

Descending pathways can suppress nociceptive transmission in the spinal cord, including through endogenous opioid signalling

Rubbing your elbow really can help:

Touch carried by Aβ fibers can recruit inhibitory circuits in the dorsal horn and partially “close the gate” on pain transmission.