Sensory Physiology

Sensory Physiology

Introduction

The sensory nervous system continuously samples the external and internal environment, converting physical stimuli into electrical signals that the brain processes to generate perception, guide movement, and maintain homeostasis. Understanding the cellular and systems-level mechanisms of sensory physiology is essential for interpreting the neurological examination and for understanding disorders from peripheral neuropathy to central sensitisation.

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Sensory Transduction

Sensory transduction is the conversion of a physical or chemical stimulus into a graded receptor potential. The key steps are:

1. Stimulus → receptor potential: A stimulus deforms a mechanosensitive channel, activates a GPCR, or opens a ligand-gated channel in the sensory receptor cell → local depolarisation (receptor potential)
2. Receptor potential → action potential: If the receptor potential is large enough to depolarise the initial segment of the sensory neuron to threshold → AP generated (all-or-none)
3. Encoding: Stimulus intensity is encoded in AP frequency (rate coding); stimulus duration encoded in the pattern of adaptation; stimulus location encoded by which sensory neuron fires (labelled line)

Adaptation: Tonic (slowly adapting) receptors respond throughout stimulus duration — encode stimulus magnitude and duration (Merkel discs, Ruffini endings). Phasic (rapidly adapting) receptors respond only at stimulus onset and/or offset — detect change and movement (Meissner's, Pacinian).

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Mechanoreceptors of the Skin

Four major mechanoreceptor types in glabrous (hairless) skin, classified by receptive field size and adaptation rate:

Meissner's corpuscles (RA1 — rapidly adapting, small receptive field):

• Location: dermal papillae of fingertips, lips
• Structure: encapsulated end organ; stacked lamellae of Schwann cells around axon terminal
• Function: detection of light touch, texture (fine spatial discrimination), slip detection (critical for grip); flutter vibration ~30 Hz
• Clinical: most densely packed in fingertips (two-point discrimination ~2–3 mm); reduced in ageing

Pacinian corpuscles (RA2 — rapidly adapting, large receptive field):

• Location: deep dermis, periosteum, joints, viscera, genitalia
• Structure: large onion-like concentric lamellae; most complex encapsulation; rapidly transmit then absorb deformation → phasic response
• Function: vibration detection (best 200–300 Hz), deep pressure, high-frequency vibration transmitted via tools
• Large receptive field → poor spatial discrimination but excellent for vibration through objects

Merkel discs (SA1 — slowly adapting, small receptive field):

• Location: basal epidermis, fingertips, lips; associated with Merkel cells (neuroendocrine epithelial cells)
• Function: fine spatial detail, texture, sustained pressure; highest two-point discrimination (fingertip)
• Slowly adapting — continue to fire throughout sustained stimulus

Ruffini endings (SA2 — slowly adapting, large receptive field):

• Location: deep dermis, joint capsules
• Function: skin stretch, joint position sense, hand conformation

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Proprioception

Muscle spindles (Ia and II afferents):

• Structure: intrafusal muscle fibres (nuclear bag — Ia, dynamic; nuclear chain — both Ia and II) within a connective tissue capsule, enclosed within extrafusal muscle
• Ia afferents (primary endings): Annulospiral endings on nuclear bag and chain fibres; large-diameter Aα (Group I) fibres; respond to rate of change of muscle length (velocity) → dynamic stretch reflex
• II afferents (secondary endings): Flower-spray endings on nuclear chain fibres; respond to muscle length (static) → tonic stretch reflex
• Gamma motor neurons (Aγ) set intrafusal fibre tension, maintaining spindle sensitivity across the range of muscle length; essential for gain control
• Clinical: loss of spindle afference → hyporeflexia; spasticity → upregulated stretch reflex (UMN lesion → loss of descending inhibition of stretch reflex arc)

Golgi tendon organs (Ib afferents):

• Located at musculotendinous junction; in series with extrafusal muscle fibres
• Respond to muscle tension (force); large-diameter Ib myelinated fibres
• Inhibit agonist α-motor neurons (Ib inhibitory interneurons — autogenic inhibition) → protective reflex preventing excessive force generation
• At very high force: clasp-knife response (relaxation of spastic limb on sustained stretch)

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Pain Pathways (Nociception)

Nociceptors are free nerve endings that respond to tissue-damaging stimuli. Two afferent types:

• Aδ fibres: Thinly myelinated (conduction velocity 5–30 m/s); respond to sharp, well-localised mechanical and thermal pain (first pain)
• C fibres: Unmyelinated (0.5–2 m/s); respond to burning, dull, aching pain (second pain); also carry temperature (warm) and itch signals; polymodal (mechanical, thermal, chemical)

Spinal cord processing:

• Nociceptive afferents enter the spinal cord via the dorsal root, synapse in the dorsal horn (Rexed laminae I, II)
• Lamina I (marginal layer): receives Aδ and C fibre input; projection neurons
• Lamina II (substantia gelatinosa): primarily interneurons; critical for modulation
• Primary afferents release glutamate (fast) and substance P / CGRP (slow, sustained) onto dorsal horn neurons

Anterolateral system (spinothalamic tract):

• Dorsal horn neurons cross the midline via the anterior white commissure within 1–2 spinal segments → ascend in the contralateral anterolateral funiculus → synapse in the ventral posterior lateral nucleus (VPL) of thalamus → primary somatosensory cortex (SI)
• Also projects to intralaminar thalamic nuclei → anterior cingulate cortex (affective component of pain)

Gate control theory (Melzack and Wall, 1965):

• Large-diameter mechanoreceptive afferents (Aβ) activate inhibitory interneurons in lamina II (substantia gelatinosa) that presynaptically inhibit C fibre transmission → "gate closed" to pain
• Explains why rubbing an injury reduces pain; basis of TENS (transcutaneous electrical nerve stimulation)

Descending inhibition:

• Periaqueductal grey (PAG) receives input from cortex, hypothalamus, limbic system
• PAG neurons project to the rostral ventromedial medulla (RVM, including nucleus raphe magnus) and the noradrenergic locus coeruleus
• RVM releases serotonin (5-HT) onto dorsal horn → inhibits nociceptive transmission (via 5-HT1B/D and interneuron activation)
• Locus coeruleus releases noradrenaline → activates α2 receptors on dorsal horn neurons → inhibition
• Endogenous opioids (enkephalins, β-endorphin, dynorphin) act at μ, δ, κ opioid receptors on presynaptic C fibre terminals and dorsal horn neurons → reduced substance P release and hyperpolarisation
• Clinical: opioids mimic endogenous system; TCA/SNRI drugs enhance NA/5-HT descending inhibition (useful in neuropathic pain)

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Referred Pain

Referred pain is perceived at a site distant from the actual injury, due to convergence of visceral and somatic afferents on the same dorsal horn neurons (convergence-projection theory). The brain misinterprets the visceral input as cutaneous. Examples:

• Cardiac ischaemia → left jaw, shoulder, inner arm (T1-T4 dermatomes)
• Diaphragmatic irritation → shoulder tip (C3-C5; phrenic nerve)
• Appendicitis → periumbilical initially (T10 dermatome), then right iliac fossa when parietal peritoneum involved

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Phantom Limb and Central Sensitisation

Phantom limb: Perception of sensation (often pain) in an amputated limb. Mechanisms include: peripheral ectopic discharge from neuroma, spinal disinhibition, and cortical reorganisation (adjacent cortical areas of somatosensory cortex invade the deafferented limb area). Mirror therapy and graded motor imagery target cortical reorganisation.

Central sensitisation: Persistent nociceptive input leads to long-lasting increase in excitability of dorsal horn neurons (wind-up, LTP-like mechanisms at dorsal horn synapses — NMDA-dependent). Features: allodynia (non-painful stimulus causes pain), hyperalgesia (enhanced response to painful stimulus), spread beyond the injury site. Relevant in chronic pain syndromes (fibromyalgia, CRPS). Treatments targeting central sensitisation: gabapentinoids (block α2δ subunit of voltage-gated Ca2+ channels — reduce presynaptic glutamate release), ketamine (NMDA block), SNRIs.