7. The somatosensory system Flashcards
What is a modality?
A type of stimulus e.g. hot, cold, touch
What are the specialised receptors for the following:
• Touch
• Proprioception (joint position, muscle tension)
• Temperature
• Pain
- Touch - mechanoreceptor
- Proprioception - mechanoreceptor
- Temperature - thermoreceptor
- Pain - nociceptor
What are the 3 main categories of sensory fibres?
- Mechanoreceptors of the skin (Aβ) - very fast (large, myelinated)
- Pain, temperature (Aδ) - slighly fast (myelinated)
- Pain, temperature, itch (C) - slow transducing (no myelination)
How are nerve endings different in thermoreceptors, nociceptors and mechanoreceptors?
- Thermoreceptors/nociceptors - free nerve endings (C fibres)
- Mechanoreceptors - encapsulated nerve endings (Aβ)
What is the absolute threshold?
Stimulus strength required to produce a positive response of detection 50% of the time
How does a stronger/longer stimulus affect the action potential and neurotransmitter release?
- Larger generator potentials
- Faster and more train of action potentials
- More neurotransmitter released
Describe thermoreceptors
• Free nerve endings with high thermal sensitivity
• Change in temperature activates transient receptor potential (TRP) ion channels
• Have transmembrane portions:
- 4 heat-activated TRP channels (TRPV 1-4): ranging from noxious to tepid heat
- 2 cold-activated TRP channels: TRPM8 + TRPA1
• Combination of different receptor types on nerve endings
Describe the different mechanoreceptor endings
- Meissner’s corpuscle - fine discriminative touch
- Merkel cells - light touch and superficial pressure
- Pacinian corpuscle - deep pressure, vibration and tickling
- Ruffini endings - continuous pressure or touch + stretch
What are adaptations and name 2 types?
- How the skin transmits signals, and how the brain interprets them
- Tonic and phasic receptors
Describe tonic receptors
- Detect continuous stimulus strength
- Adapt slowly/do not adapt
- Continue to transmit impulses as long as the stimulus is present
- Keep brain constantly informed
- e.g. Merkel cells slowly adapt - allows for fine touch to be perceived
Describe phasic receptors
- Detect a change in stimulus strength
- Transmit an impulse at the start and the end of a stimulus
- Also called “movement receptors” or “rate receptors”
- e.g. pacinian receptor
What is a receptive field?
• Region on the skin that causes activation of a single sensory neurone
• Different parts of the body have different sizes of receptive fields
• Smaller field:
- densely packed neurones
- precise perception
- more likely to recognise 2 points of touch
Describe Aδ nociceptors
- Myelinated - quite fast
- Type 1: Aδ-mechano-heat receptors (noxious mechanical and thermal stimuli)
- Type 2: Aδ-mechanoreceptors (purely noxious mechanical stimuli)
Describe C-fibre nociceptors
- Unmyelinated - slow
- Mediate dull, persistent or second pain
- Respond to thermal, mechanical and chemical stimuli (polymodal)
- Chemical stimuli include inflammatory mediators
Where are the cell bodies of afferent neurones?
- Dorsal root ganglia in the body
* Trigeminal ganglia in the face
Where do the 3 fibres enter the dorsal horn of the spinal cord?
- Innocuous mechanical stimuli - Aβ (+Aα) - terminate in lamina III-VI (deep dorsal horn)
- Pain and temperature - Aδ + C-fibres terminate in lamina I-II (superficial dorsal horn)
What is the main excitatory neurotransmitter released from the pre-synaptic neurone within the dorsal horn?
- Glutamate
* Then transmits to the brain
What is the role of interneurones in the dorsal horn?
- Conenct between different laminae and between adjacent peripheral inputs
- Modulate pain and transmit mechanical stimulation through the dorsal horn
What is lateral inhibition?
- Receptive fields can overlap with each other - difficult to distinguish between 2 stimulus locations
- Lateral inhibition prevents this
- Mediated by inhibitory interneurones within dorsal horn of spinal cord
- Also facilitates enhanced sensory perception
What is gate control theory?
- You can modulate a pain response in the dorsal horn by activating an Aβ-fibre
- Aβ-fibre - involved with innocuous mechanical stimulation
- If you hurt yourself, you ‘rub it better’ - assimilates Aβ-fibres - inhibits stimulated pain fibres
What are 3 of the central sensory structures in the brain?
- SI: Primary somatosensory cortex (in postcentral gyrus)
- SII: Secondary somatosensory cortex (in parietal operculum)
- Posterior parietal cortex - spatial awareness
How do sensory inputs get into the brain? (2 pathways)
- Dorsal column system (touch and proprioception)
* Spinothalamic pathway (pain, temperature and crude touch)
Describe how Aβ-fibres enter the dorsal column system?
- Enter via the dorsal horn and enter ascending dorsal column pathways
- Information from lower limbs (below T6) travel ipsilaterally along the gracile tract
- Information from the upper limbs travel ipsilaterally along the cuneate tract
Describe how Aβ-fibres travel through the dorsal column system once entered each tract, with reference to each order
1st order neurones
• Fibres in the Gracile/Cuneate Tract first synapse in the Gracile/Cuneate Nucleus (in the medulla)
2nd order neurones
• Decussate (cross sides) in the caudal medulla
• Forms the contralateral medial lemniscus tract
• Terminate in the thalamus (ventral posterolateral nuclei) - topographic: lower extremities more lateral
3rd order neurones
• Project from the VPL to the somatosensory cortex
• Size of somatotopic areas is proportional to density of sensory receptors in that body region (somatosensory homunculus)
• Pain and temperature localisation not as precise
What are the 2 different pathways within the spinothalamic tract?
- Lateral - pain and temperature
* Anterior - crude touch
Describe how neurones travel through the spinothalamic tract
1st order neurones
• Terminate upon entering the spinal cord - i.e. dorsal horn
2nd order neurones
• Decussate immediately in the spinal cord
• Form the spinothalamic tract
•Terminate in the thalamus (ventral posterolateral nucleus) - topographic
What are the key differences between the dorsal column and spinothalamic tract?
Dorsal column tracts
• Transmits light touch, vibration and 2-point discrimination
• Cross in brainstem
Spinothalamic tracts
• Transmits pain, temperature and coarse touch
• Cross in spinal cord
How does pain reach the limbic system, giving it its emotional aspect?
- Emotional component of pain transmitted from the spinal cord to the parabrachial area - then to the limbic system
- Spino-reticular system
- Sensory component bypasses the parabrachial area and goes to the cortex
What is the cerebral signature for pain in an fMRI?
- Loss of activity in the cortex - SI, SII, Insula, cortex, anterior cingulate cortex, prefrontal cortex
- Amygdala, cerebellum and brainstem have more activity
What is quantitive sensory testing (QST)?
- Use of tools to look into different modalities e.g. temperature thresholds, vibration sensitivity
- Allows us to look at whether or not the sensory system is sensitised/any pathology
What can a blocked anterior spinal artery lead to?
- Ischaemic damage to anterior part of the spinal cord - lesion of spinothalamic tract
- Pain and temperature loss below level of the lesion
- Retained light touch and vibration due to intact dorsal columns
How are electrical perceptual thresholds different to QSTs?
- Like QST, but use a semi-automated method - electrical current passed through the skin
- Ask patient whether or not they can feel it - can then map the whole body
- Spinal cord injury - lose sensation - threshold goes up
What is pain?
An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage
What are 6 types (causes) of pain?
- Nociceptive - tissue damage, typically acute pain
- Muscle - lactic acidosis, ischaemia e.g. stretching
- Somatic - well-localised e.g. inflammation
- Visceral - deep, poorly localised
- Referred - from an internal structure
- Neuropathic - dysfunction of the nervous system
What is neuropathic pain?
- Pain caused by a lesion or disease of the somatosensory nervous system
- Typically sharp, burning “electric shocks”
- Poor response to usual analgesic drugs e.g. opiates
Give examples of neuropathic pain
- Radicular pain (sciatica)
- Diabetic neuropathy
- Post-surgical pain
- Chemotherapy induced neuropathy
What is allodynia?
Pain due to a stimulus that does not normally provoke pain
What is hyperalgesia?
Increased pain from a stimulus that normally provokes pain
What is sensitisation?
• Increased responsiveness of nociceptive neurones to their normal input
What is hypoalgesia?
Diminished pain in response to a normally painful stimulus
What is paraesthesia?
Abnormal sensation, whether spontaneous or evoked
If you repeat a stimulus a number of times, it becomes more painful, what are the underlying mechanisms for this called?
- Central sensitisation
* Happens in the dorsal horn
What can persistant activation of the NMDA receptor lead to?
• Development of chronic pain e.g. arthritis
• NMDA receptors are involved with inducing plasticities in the CNS
- they allow big post-synaptic depolarisation
- Ca2+ mediated synaptic plasticity in dorsal horn neurones
- increased sensitivity
• Inhibitory interneurons can become less influential in chronic conditions
• Persistant activation causes stimuli to become more painful
Describe the neuropathic phenotype profile?
- Sigmoidal graph - stimulus intensity vs pain intensity
- Following injury - graph shifts left - higher pain with lower stimulus
- Allodynia - area where there is pain following injury where the pain intensity was previously 0
- Hyperalgesia - higher pain at low stimulus intensity
What are the 2 main types of neurotransmitters in the brainstem (that inhibit spinal cord excitability)?
- Serotonin (from serotonergic nuclei, medulla)
* NA (from noradrenergic neruones, pons)
What are the 2 types of descending control of nociception?
- The PAM-RVM axis
* The locus cereleus (LC)
What is the role of the PAM-RVM axis
• Contains serotonergic neurones, which project into the dorsal horn releasing serotonin
• Can either inhibit or facilitate pain depending on which receptors are activated:
- 5-HT1a: predominantly inhibitory
- 5HT3: predominantly facilitatory on NT release
What is the role of the locus cereleus?
- Main noradrenergic nuclei involved with descending control of nociception in the dorsal horn
- Predominantly inhibitory
- Dampens response by binding to pre-synaptic α2 receptors on primary afferents and projection neurones
Describe how endogenous opioids work?
• The PAG and RVM contain high concentrations of μ opioid receptors
• Endogenous opioids (enkephalin, dynorphin) enhance descending inhibition from the PAG-RVM axis
• Reduce pain transmission in the dorsal horn
- inhibit glutamate release
- inhibit activation of spinothalamic neurones
What effect does placebo have on pain?
- Placebo induced analgesia is another form of endogenous analgesia
- RAG and RVM show activity
- Assume the spinal cord is involved - either inhibited or facilitated
How can descending control systems be targeted for pain relief (medication)?
• Opioids - work in the PAG and RVM
• Antidepressants treat neuropathic pain (TCA, SNRI, SSRI)
- SSRIs are not very effective - low analgesic efficacy
- amitriptyline (TCA) is widely prescribed for neuropathic pain due to its noradrenergic component
How do SNRIs provide pain relief?
- Damaged primary afferent neurone => increased excitability => central sensitisation in spinal cord
- Antidepressant binds to pre or post-synaptic terminal in the dorsal horn
- NA increases in synaptic cleft - binds to α2 receptors - inhibitory
- Sensory input to the brain is reduced - less pain
What is conditioned pain modulation
• Experimental measure of the endogenous pain inhibitory pathway in humans
- level of descending control
• Good descending control - better efficacy of duloxetine (SNRI)
What is tDCS?
- Transcranial direct current stimulation
- Non-invasive brain stimulation
- Changes in cortical excitability in M1 have been show to reduce chronic pain in fibromyalgia and migraine patients
- Mechanism not understood
How is QST being changed for the future of pain control?
• QST has been expanded - 13 different tests to tease out patient’s phenotype
• 3 different neuropathic phenotypes:
- sensory loss, thermal hyperalgesia and mechanical hyperalgesia
• e.g. opioids feasible for patients with thermal hyperalgesia
