What does the somatosensory system mediate?
Sensations from the whole body surface, including skin and deeper tissue.
What type of skin is found on the palmar surface of the hands and feet?
What is a prominent feature of glabrous skin?
What are the 4 types of mechanoreceptors found in glabrous skin?
- Meissner corpuscles
- Merkel complexes
- Ruffini organs
- Pacinian corpuscles
Which mechanoreceptors are found close to the surface of the skin?
Meissner corpuscles and Merkel complexes
Which mechanoreceptors are found deeperin the skin?
Ruffini organs and Pacinian corpuscles
Where are the somata for skin mechanoreceptors found?
In the dorsal root ganglia
What does transmission of mechanoreceptor information to the brain generate?
The conscious experience of touch
Where in the superficial layers of the skin do the Meissner corpuscles lie?
In the peaks of the dermal waves.
Where in the superficial layers of the skin do the Merkel complexes lie?
In the epidermis border
Which part of the Merkel complex is the transducer?
The nerve ending, not the Merkel cell.
What type of energy do mechanoreceptors sense?
Distortion of skin
What is the structure of the mechanoreceptors?
Various encapsulated nerve endings
What is the range of the mechanoreceptors?
10nm to sub-damaging distortion
What is the sensitivity and dynamic range of mechanoreceptors?
What is the receptive field of the mechanoreceptors?
Ovaloid from 10mm2 to the entire hand.
How does transduction in the mechanosensory afferent occur?
An object touching the skin causes the sodium channels to stretch, opening them and allowing Na+ in, depolarising the cell.
Why won't all stimuli affecting the mechanoreceptor be transduced into action potentials?
Because the receptor potential must reach threshold to generate an AP.
What are the 2 ways the mechanoreceptor can respond to a continuous stimulus?
Slowly- and rapidly-adapting
How does a slowly-adapting mechanoreceptor behave?
There's an initial increased amount of nerve activity, but the frequency will reduce and remain relatively constant for the duration of the stimulus.
What do slowly-adapting mechanoreceptors inform on?
Duration of the event
How does a rapidly-adapting mechanoreceptor behave?
There's an initial increased amount of nerve activity that quickly disappears.
What do rapidly-adapting mechanoreceptors inform on?
The change (not the duration)
True or false: most receptors of the nervous system are slowly adapting.
False: the brain really only cares about changes.
Where do all mechanoreceptors have their cell bodies?
In the dorsal root ganglia of the spinal cord.
Where do all mechanoreceptors that innervate the face have their cell bodies?
In the trigeminal ganglion.
What is the major difference between tactile and nociceptive afferents?
- Tactile afferent sensation is proportional to the stimulus and is only present so long as the stimulus is.
- Nociceptive sensation remains after the stimulus is gone.
- This is desirable because you only want sensation of the stimulus so long as it is there for tactile sensation, whereas nociception informs us on the homeostatic condition of the body.
Which modalities of sensation are considered tactile?
Touch, temperature and proprioception
How do we know so much about mechanoreceptors?
From recording individual nerves using microelectrodes and stimulating the skin with probes.
How is the receptive field of a mechanoreceptor largely determined?
By the depth and structure of the receptor.
What is a common feature of rapidly-adapting mechanoreceptors?
Which of the mechanoreceptors are slowly adapting?
Merkel complexes and Ruffini endings.
Where are Merkel complexes found and what do they respond to?
Found at the tips of the epidermal ridges where they respond to indentation.
Where are Ruffini endings found and what do they respond to?
Found in the upper dermis, have a sustained response to skin movement.
Which of the mechanoreceptors are rapidly adapting?
Meissner receptors and Pacinian receptors.
Where are Meissner receptors found and what do they respond to?
Found near the skin surface and have a transient response to skin movement.
Where are Pacinian receptors found and what do they respond to?
Deep in the dermis and hypodermis
Transient response to vibration.
What are the 3 different dichotomous classifications for mechanoreceptors of the skin?
- Receptive field (big/small)
- Location (superficial/deep)
- Functional properties (rapidly-adapting/slowly-adapting)
Which mechanoreceptor has the smallest receptive field, is located superficially and is slowly adapting?
Which mechanoreceptor comprises 40% of the total mechanoreceptors of the hand?
Which mechanoreceptors have a high density?
Merkel and Meissner
Which mechanoreceptors are located deep in the hand?
Ruffini and Pacinian
Which mechanoreceptors comprise 20% of the mechanoreceptors of the hand?
Which mechanoreceptors have a low density in the hand?
Ruffini and Pacinian
Which mechanoreceptor is the most sensitive?
Which mechanoreceptor senses vibration?
Which mechanoreceptor is proprioceptive?
What does each mechanoreceptor encode for?
- Meissner encode rate of force
- Merkel encode grip force
- Pacinian encode vibrations
- Ruffini encode hand posture
What is the two-point discrimination threshold?
The minimum distance at which two points stimulating the skin can be perceived as two individual points instead of one.
When is the two-point discrimination threshold used clinically?
To understand successful reinnervation after nerve injury.
What does sensory discrimination depend on?
The entire system, peripheral and central mechanisms
Which nerve fibre type is used for touch?
Which nerve fibre type is used for proprioception?
Which nerve fibre type is used for pain, temperature and itch?
Which nerve fibre type has the fastest conduction velocity?
Iα and II - 80-120m/s
Which nerve fibre has the slowest conduction velocity?
Why do C-fibres have the slowest conduction velocity?
Being unmyelinated, this consumes less space, allowing for more axons in the nerve and ultimately a higher resolution
Where are the cell bodies of the mechanoreceptors?
In the dorsal root ganglion.
Where are the cell bodies of the pain and temperature primary afferents?
In the dorsal root ganglion.
In which white matter tract do mechanoreceptor nerve fibres pass to the brain?
In which white matter tract do pain and temperature nerve fibres pass to the brain?
In the spinothalamic tract of the anterolateral system
Where do fibres entering from lower parts of the body (feet and hind limbs) travel in the spine generally?
Where do more rostral fibres entering the spinal cord tend to travel?
Fibres entering from which region travel the most laterally in the spinal cord?
From the cervical level.
What is a fasciculus?
An area within the spinal cord in which branches for local connections communicate.
Where do all pathways up the spinal cord project up to?
Where does the tactile pathway decussate?
In the caudal medulla
What is the end point for the tactile pathway?
Where does the primary afferent of the tactile pathway make synapse?
Onto neurons in the dorsal column nuclei of the medulla
Which two nuclei in the dorsal column of the medulla do tactile afferents synapse onto?
Gracile (medial) and cuneate (lateral) nuclei.
What happens to axons arising from the gracile and cuneate nuclei of the dorsal column in the medulla in the tactile afferent pathway?
Where do the axons from the gracile and cuneate nuclei travel in the tactile afferent pathway?
To the ventral posterolateral thalamus via the internal arcuate fibres and the medial lemniscus.
Where does the tactile afferent pathway decussate?
Between the dorsal column nuclei and the ventral posterolateral thalamus via the internal arcuate fibres.
Where do the axons from the ventral posterolateral thalamus of the tactile afferent pathway travel?
To somatosensory cortex S1 in the post-central gyrus.
Tactile afferents from which parts of the body synapse onto the gracile nucleus?
Axons from the lumbar region and lower limb
Tactile afferents from which part of the body synapse onto the cuneate nucleus?
Axons from the thoracic region and upper limb.
Describe the entire pathway of information from the mechanoreceptor to the cerebrum.
- Action potential conducts along primary afferent from mechanoreceptor.
- Travels up dorsal column and synapses at dorsal column nucleus.
- Secondary afferent decussates from caudal medulla via the internal arcuate fibres to the ventral posterolateral thalamus via the medial lemniscus pathway where it synapses on the VPL nucleus.
- Tertiary afferent projects ipsilaterally from the VPL nucleus to the cerebral cortex in S1 in the postcentral gyrus.
Other than via the posterior column-medial lemniscus pathway, where else does information from the mechanoreceptors synapse?
Locally in the spinal cord and onto the cerebellum.
Which Brodmann area is at the precentral gyrus
Which Brodmann area is at the postcentral gyrus?
How is the somatosensory cortex ordered?
- It's ordered into different regions of the body from medial to lateral
- The size of the region is inconsistent
What determines the amount of somatosensory cortex a particular body region has?
How much somatosensory information is coming from the region.
Which maps of the body surface are somatotopic?
All 4 maps of the body surface, as well as the 4 in S2 and 2 in the posterior parietal cortex.
What are the 4 different areas of the primary somatosensory cortex (S1)?
- Area 1
- Area 2
- Area 3a
- Area 3b
What do neurons in the primary somatosensory cortex form?
Functionally distinct columns
Which afferents in the mechanoreceptor pathway are ipsilateral and which are contralateral?
- Primary afferent is ipsilateral.
- Secondary and tertiary afferents are contralateral.
Are the different types of mechanoreceptor segregated in the somatosensory cortex?
Which map in primary somatosensory cortex receives most of the inputs from the ventral posterior complex of the thalamus?
What is area 1 of the somatosensory cortex supposedly concerned with?
What is area 2 of the somatosensory cortex supposedly concerned with?
Which maps in S1 contribute to cognitive touch in S2 cortex and then further on to the amygdala and hippocampus?
1, 2, 3a and 3b (i.e. all)
Which map in S1 projects to parietal areas 5 and 7 and further on to motor and premotor cortical areas?
What are the 4 different parameters in cortical representations?
- Duplication (multiple maps)
Which is quantitatively the most important region in S1, i.e. a lesion in which S1 map will result in lesions in almost all forms of somatosensation?
Why do all of the maps project into the amygdala and hippocampus?
To facilitate memory and learning, e.g. object recognition
How is the barrel field in mice an example of modularity in the cortex? What is another animal that exhibits this?
Each whisker on the mouse has its own discrete cortical representation, instead of all whiskers having cortical representations spread among themselves. Another example of this is in the fleshy nosed mole.
Which functional changes in the somatic sensory cortex are seen following amputation of a digit?
Neurons from neighbouring cortical digits will spread into that redundant region.
Which functional changes in the somatic sensory cortex are seen following amputation of a digit?
The cortical territories for the respective digits expand whilst adjacent cortex will shrink.
How are lactating rats an example of plasticity in the cortical representation of the skin surface?
The somatosensory cortical representation of nipples in rats is greater when they are lactating (and their offspring suckling). Outside of this period, the cortical representation shrinks.
True or false: erroneous peripheral nerve regeneration produces compensatory central plasticity.
- Erroneous peripheral nerve regeneration does not produce compensatory central plasticity.
- Central plasticity can't rethink what the periphery has done.
True or false: Peripheral and CNS nerves readily regrow
- Peripheral nerves readily regrow, but CNS nerves don't.
What stops CNS neurons regrowing?
They stop growing when they encounter a lesion site.
What is a normal outcome after a limb amputation?
Why does phantom limb occur?
- Just because a peripheral nerve is lost, it doesn't mean the central representation of the body has changed.
- The peripheral nerves are for direct contact with the environment, however the body representation is purely central.
- Somatosensory sensation does not tell you about the structure, rather the environment impacting on it.
- Hence, when a limb is amputated, the ability to perceive environmental stimuli is lost, however the structure (cortically) remains.
Where does the spinal cord finish?
What can be performed below the spinal cord, due to it ending before the spinal column?
Which spinal tract do pain and temperature fibres travel through?
Which spinal tract do tactile and proprioceptive fibres travel through?
What do all axons entering the spinal cord have in common?
They all make local connections in the spinal cord before they project rostrally.
Where do pain and temperature fibres decussate?
Where they enter the spinal cord.
Where do pain (C) and temperature (Aδ) fibres synapse with their second order neuron?
In the dorsal horn, when they enter.
Where do motoneurons of the spinal cord mostly reside?
In the anterior horn
What type of motoneuron are the majority of motoneurons in the spinal cord?
Which class of afferents will often also synapse with α-motoneurons in the spinal cord?
Why are motoneurons the "final common pathway?"
Because only motoneurons can innervate muscle.
How are neurons in the ventral/anterior horns of the spinal cord distributed?
- Into motoneuron pools, with medial motoneurons innervating axial/proximal muscles and lateral motoneurons innervating more distal muscles.
- This is somatotopy.
Why is there more white matter in the spinal cord rostrally?
Because moving from caudal to rostral, more and more information is coming in progressively up the spinal cord and less information leaving the spinal cord (motoneurons) moving more caudally.
What is a motor unit?
The collection of muscle fibres innervated by a single alpha motor neuron.
What is a motoneuron pool?
A cluster of neurons in the spinal cord that all supply the one muscle.
What is a muscle spindle?
- A mechanoreceptor specialised to provide sensory information on the stretch (i.e. length) of a muscle.
- It starts as a muscle fibre, but is then instructed in utero to change by 1A sensory fibres.
- Thus, it is still contractile and has a contractile innervation, but is dominated by the fibres wrapping around it, acting as transducers for muscle stretch.
- The muscle spindle is described as being in parallel with the muscle.
What does the muscle spindle detect?
- The amount of stretch on the muscle (how long the muscle is). This is a sustained, slowly adapting type of mechanoreceptor. These are α-motoneurons, reflecting the fact that these fibres are still contractile.
Change in muscle length – they don’t care how long a muscle is, but will report quickly if there is a change, thus rapidly adapting.
What is a Golgi tendon organ (GTO)?
- Proprioceptive nerve fibres embeded in the collagen matrix of muscle tendons, informing on force within the tendon.
- GTOs are in series with the muscles.
What is the principle difference between muscle spindles and Golgi tendon organs?
Muscle spindles are length/stretch transducers, whereas GTOs are force transducers.
What is the monosynaptic stretch reflex?
- Tendon is stretched, muscle pulled on, muscle spindle stimulated.
- Muscle spindle sends APs to spinal cord and through to motoneurons of same muscle, causing same muscle to contract.
- This pathway involves one synapse: that between the muscle spindle and its own muscle.
What else, other than motoneurons its own muscle, do axons from the muscle spindles synapse onto?
Interneurons which then inhibit antagonist muscles on the other side of the joint, allowing for unopposed muscle contraction.
What would happen if a muscle spindle were to experience an unexpected increase in load on its muscle?
- Disturbance causes muscle and muscle spindle to stretch.
- Muscle spindle sends train of action potential to spinal cord via group I and II afferents.
- Afferents synapse onto motoneuron of same muscle and interneuron. Interneuron synapses onto antagonist muscle.
- Agonist muscle is stimulated to contract via its alpha motoneuron, antagonist muscle is inhibited.
- Unexpected increase in load is adjusted for.
What is the principle difference between the outcome of muscle spindle stimulation and Golgi tendon organ stimulation?
The muscle spindle exists to increase muscle contraction in response to increased stretch, whereas the Golgi tendon organ exists to inhibit muscle activity in response to loads/forces that could potentially damage the tendon/muscle.
What is the difference in circuitry seen in between the muscle spindle and Golgi tendon organ?
- Muscle spindles act primarily to excite via excitatory inputs onto motoneurons.
- GTOs act primarily to inhibit muscle activity by acting via interneurons.
What is the bilateral (cross-extensor) reflex?
- A postural recovery mechanism for when there's a need to flex the limb, e.g. when stepping on something sharp.
- The limb must be withdrawn (flexed) and the other limb stabilised to take the weight of the body through extension.
What mediates coordination of bilateral (cross-extensor) reflexes up and down the spinal cord?
What are pattern-generating circuits?
- Circuits that exist solely within the spinal cord that generate specific pattern-based movements, such as walking or scratching a specific area.
- The brain acts only to activate the circuit.
How does interneuron length differ in the spinal cord?
- Medial interneurons tend to be longer (long propriospinal), because they modulate postural muscles.
- Lateral interneurons tend to be shorter (short propriospinal) because they control very fine movements of dextrous appendages.
What term is given to any neuron that affects the excitability of a lower motor neuron?
Upper motor neuron
What type of neurons does most information coming down the corticospinal tract travel via?
Why is an increase in muscle tone and muscle spasticity seen in spinal cord lesions?
- Because the majority of input from the brain is inhibitory.
- When this is lost in a lesion, inhibition is lost below the area of disruption, leading to increased tone and exaggerated spinal cord reflexes.
How can the location of a spinal cord lesion be identified?
By testing the monosynaptic reflex at different muscles.
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 the 4 steps of pain sensation?
- Transmission (peripheral to central)
- Perception (sensory, discriminative, emotional, aversive)
- Modulation (infer, as nociception does not always lead to pain.
True or false: nociception is the sensation of pain.
What distinguishes nociceptors from other mechanoreceptors or temperature receptors?
They respond only to high levels of stimulation.
What are nociceptors with their somata in the dorsal root ganglion responsible for?
Somatic and visceral pain
What are the nociceptors with their somata in the trigeminal ganglion responsible for?
Migraine, tooth ache and jaw pain
What nerve fibre types are responsible for sharp pain?
What nerve fibre types are responsible for slow/burning pain?
What is first and second pain?
- The sharp pain first felt is the first pain, the slow burning pain is the second pain.
- First pain is conducted by type IIa fibres, whereas second pain is conducted by C-fibres.
- Although both sources of the pain came at the same time, the conduction velocity means that sharp will be felt before slow burning pains.
What type of nociceptors are found on the back of the hand (hairy skin)?
Type IIa and C-fibres
What type of nociceptors are found on the palm of the hand (glabrous skin)?
What is the spinal cord divided into?
Which spinal cord laminae are nociceptor inputs confined to?
1 and 2
What is the pathway of the first and second order neurons for nociception?
Nociceptor enters the dorsal horn at lamina 1 or 2 and synapses onto projection neuron which then decussates and travels through the anterolateral system.
Where do nociceptor axons enter the dorsal root in relation to other sensory fibres?
True or false: spinal nociceptive reflexes = pain.
What percentage of nociceptive neurons project to the brain?
- 90-95% only project within the spinal cord and don't go to the brain.
How do spinal nociceptive reflexes work?
- Nociceptive neurons synapse onto second order neurons in the dorsal horn, which then synapse third order neurons located deeper in the dorsal horn.
- These then make connections with motoneurons projecting out of the spinal cord and back to muscles.
True or false: the spinal nociceptive reflex requires input from the brain.
What are the 3 classes of nociceptive pain?
Thermal, mechanical and chemical.
What is the key difference between inflammatory pain and mechanical pain?
Inflammatory pain is spontaneous pain in the absence of stimulation from noxious sources and there's a change in the encoding of pain, known as pain hypersensitivity.
What is inflammatory soup?
The nociceptor sensitisers released by inflamed or damaged tissue that act to stimulate the nociceptor.
What is TRPV1 the nociceptive transducer for?
What happens when TRPV1 is activated?
Channel opens and lets Ca2+ and Na+ in, depolarising the nerve terminal, generating an AP.
What else can TRPV1 be activated by?
Noxious levels of heat (>42 degrees) or by acidification (H+).
True or false: The TRP channels have many different sub-types and can be activated by different stimuli.
What are the different categories of nociceptors expressing different mixtures of TRP channels?
- Polymodal - peptidergic, non-peptidergic
What is peripheral sensitisation?
The inflammatory soup acting on the transducers can change the sensory property of the nociceptor, changing them in a way that either responds to noxious stimuli or innocuous stimuli.
What is central sensitisation?
- Peripheral sensitisation can have a cascade.
- The change in activity caused by sensitisation can cause neuroplasticity in the CNS, referred to as central sensitisation.
- These two processes are separate, but the net effect is similar.
- They can cause hyperalgaesia or allodynia.
What is hyperalgesia?
An increased response to a normally painful stimulus.
Why is allodynia?
A painful response to a normally innocuous stimulus.
What is secondary hyperalgesia?
- Sensitisation also causes a spatial expansion of pain sensitivity.
- Secondary central sensitisation with the spinal cord can recruit other populations of sensory nociceptors that innervate the surrounding areas and create secondary hyperalgaesia or amplification of pain responses in that area.
What are the 2 major types of maladaptive pain?
Neuropathic and dysfunctional
What is neuropathic pain associated with?
Nerve damage (occuring either in a peripheral nerve or during a CNS injury)
What type of maladaptive pain are myalgia and endometriosis?
What is the difference between maladaptive pain and other types of pain?
There are no neural lesions or inflammation, but there is a change in the way the pain is processed.
What is peripheral neuropathic pain?
- When there's damage to a peripheral nerve (e.g during surgery), nerve terminals can start generating spontaneous (ectopic) pain activity.
- There can also be a pathological neuroplasticity in the spinal cord or brain. All of these things together can interact and the peripheral processes can cause a cascade towards the central processes occurring.
True or false: it is possible to look at an MRI and tell if someone is in pain.
What are the most important cortical areas for pain perception?
Somatosensory cortex, insular cortex and cingulate cortex.
What are the major classes of centrally acting analgesic drugs?
Anticonvulsants (gabapentin, pregabalin)
CAs (tricyclic antidepressents)
α2-adrenergic agonist (clonidine)
SNRIs (Serotonin-noradrenaline reuptake inhibitors)
What is the central pathway for pain?
Anterolateral system → rostroventral medulla (RVM) → Periaqueductal grey (PAG) → Somatosensory/insular/cingulate cortex
True or false: the brain is capable of modulating the transmission of pain-related information from the spinal cord.
- It can interrupt the flow of information from the nociceptor to the ascending pathway.
What does spinal control of pain provide?
- Modulation and negative feedback control by modulating nociceptive transmission in the spinal cord.
- This feedback system is used towards the end of inflammation and other processes as a way of turning off the increased pain sensitivity.
True or false: the anticipation of physical pain is enough to activate the descending pain modulation system?
Which system is activated directly by analgesic drugs?
The descending pain modulation system
Which cortical areas are associated with top-down psychological modulation of pain?