01 Pain Processing Flashcards
What are the 4 types of mechanoreceptors and how are they distributed in the skin?
- Merkel cells (25%, epidermis, especially rich in finger tips)
- Meissner corpuscles (40%, dermis)
- Ruffini corpuscles (20%, dermis)
- Pacinian corpuscles (10-15%, dermis/subcutaneous layer)
What is the afferent axon type of all mechanoreceptors?
Abeta
What are mechanoreceptors sensitive to?
- sensitive to deformation by vibration at different frequencies
What are the receptors for proprioception and what are their afferent axon types?
- muscle spindles
- afferent axon type: Ia, II
Order the sensory functions proprioception, touch, pain, temperature and itch according to their axons’s conduction velocity! What is the reason for these differences?
- proprioception > touch > pain, temperature > pain, temperature, itch
- better myelination leads to higher conduction velocity
How do the different mechanoreceptors react to stimulation?
- Merkel & Ruffini: slowly adapting, constant stimulus elicits constant response
- Meissner & Pacinian: rapidly adpating, stimulus change elicits response
What is the pathway for proprioceptive and tactile information?
- first-order neurons ascend ipsilaterally through dorsal root ganglia
- second-order neurons are situated in the brainstem
- relay in thalamus to primary somatosensory cortex (S1), S2 and parietal association cortex
Which areas belong to S1?
- Broadmann areas 1, 2, 3a and 3b
- 3b receives bulk / majority of input
What happens in S2 and parietal association cortex?
- integration of tactile object features for recognition by touch (stereognosis)
- binding of tactile with other features (vision, sound)
- higher-order interpretations
What is stereognosis?
ability to perceive and recognize form of an object by using only tactile information
How are body parts mapped onto S1 and S2?
in S1:
- medial: legs, feet, genitalia, trunk neck, head, shoulders
- lateral: face, hands
in S2:
- throat, tongue, teeth, jaw, gums
What body parts are most/least sensible to touch? (receptor density)
mean two-point discrimination threshold
- lowest in hands (2mm) and face (lower part)
- highest in shoulders and calves (45mm)
What is nociception?
perception of potentially harmful stimuli
How is pain encoded? What are pain receptors?
pain not coded in excessive action of somatosensory receptors, but in distinct perception and signaling pathway
- receptors: no specialized corpuscles, but free nerve endings
What are the 2 phases of pain and why do they exist?
- first pain: sharp and clearly localized
- second pain: dull and diffuse
- 2 different fiber types: poorly-myelinated (Adelta) and unmyelinated (C)
What are the 3 stages of pain processing?
- transduction: conversion of nociceptive stimuli into electrial or chemical (neuronal) signal (peripheral nervous system)
- transmission: forwarding of peripheral input through various notes of nociceptive pathway (sensory and postsynaptic neurons) towards the brain
- modulation: remodeling (down-/upregulation) of nociceptive information at all relay points, translation into framework including specific context and memories
Where can pain modulation occur?
at all relay points: sensory neuron, dorsal horn, higher-order brain regions
Where does pain occur?
- pain perception occurs in the brain
- “nociception and pain can each happen without the presence of the other”
Which role does the transient receptor potential (TRP) family play in pain? How do they work?
- large group of pain receptors
- mostly highly-selective Ca2+ channels, either open or closed
- opening (Ca2+ influx) favors nociceptive signal generation (action pot.)
- evidence for variation in width of opening
- some TRP may react to temperature-dependent deformation or binding of chemical agents (such as capsaicin)
- mutations of TRP proteins can lead to complete pain insensitivity or gain of function with chronic pain syndromes
- genetic variants of TRP types associated with migraine
What is the pathway for pain information?
- neural cell bodies of free nerve endings reside in paravertebral ganglia
- second-order neuron are situated in the spinal chord at the level of entry
- second-order axon crosses midline and ascends contralaterally to thalamus
What might unilateral damage to the spinal chord produce?
Brown-Séquard syndrome
- ipsilateral deficits in touch and proprioception (plus ipsilateral paresis)
- contralateral deficits in nociception and thermoception
How can referred pain be explained?
- some second order nociceptive neurons receive pain information from both a dermal segment and an inner organ
- pain arising from the inner organ cannot be distinguished from pain arising from the skin and is perceived as coming from the surface
- typical example: pain perceived in left arm as symptom of cardiac ischemia
How is pain sensitization increased?
- tissue damage
- local cells (derived from blood or resident tissue) release “inflammatory soup” of mediators (e.g. histamine, prostaglandins) causing swelling, increased blood flow and lowered pain threshold
- some TRP channel proteins become unlocked at temperatures > 50°C by permanent conformation changes and will then signal temperatures > 30°C
- effect: protection of area and promotion of healing
What are hyperalgesia and allodynia?
- hyperalgesia: abnormally increased sensitivity to pain
- allodynia: pain caused by stimulus that does not normally elicit pain
How can pain be modulated?
- placebo administration can relieve pain, but effect can be blocked by naloxone (opioid antagonist)
- pain modulating fibers arise predominantly from periaqueductal gray of midbrain and regulate activity of the synapse between first- and second-order neuron
- local collaterals from somatosensory fibers within the spinal chord can modulate pain (e.g., rubbing the site of injury)
- pain relief is mainly promoted by endogenous opioids (endorphins, dynorphins, enkephalins) and endocannabinoids (act on TRP)
- testosteron has pain dampening effect
What does the homunculus show?
receptor density
