The Somatosensory system and chronic pain

Question 1

Define the somatosensory modalities

Answer 1

type of sensory stimulus - touch, temperature, nociception, proprioception

Question 2

What are the receptors for these modalities

Answer 2

touch - mechanoreceptor, temperature - thermorecpetor

nociception - nociceptor

Question 3

Describe the structure of mechanoreceptors

Answer 3

Merkel disks is for light touch and superficial pressure,
Meissner’s corpuscles is for fine discriminative touch
Ruffini endings is for continuous pressure of touch or stretch
Pacinian corpuscles is for deep sustained pressure vibration and tickling

Question 4

Describe thermoreceptors

Answer 4

specific temperature activate family of transient receptor potential (TRP) channels 
heat -activated : 1,2,3,4, 
cold-activated : TRPM8, TRPA1 
TRPV1 - activated by capsaicin 
TRPM8 activated by cold substances

Question 5

Describe Nociceptors

Answer 5

respond to damaging or potentially damaging stimuli
There are three types
Thermal (extreme temp)
mechanical (intense pressure)
Polymodal (respond to thermal, mechanical and chemical)

Question 6

How are itch stimulated

Answer 6

due to low frequency firing of ncociceptors
specific receptors sensitive to histamine which produce the unpleasant sensation that urges us to scratch and inducing pain

Question 7

How do receptors generate an electrical signal from a physical or chemical stimulus ?

Answer 7

• receptors have specific cation channels on the nerve endings membrane, which open in response to the stimulus and if intensity of stimulus is high enough to reach threshold for activating sodium channels, and lead to depolarisation and any depolarisation above the threshold will induce a train of action potentials. Each action potential causes release of neurotransmitters at the synapse with the second neuron of the afferent pathway

Question 8

What happens when there is a longer and stronger stimulus

Answer 8

1. A stimulus of greater duration and amplitude will induce a larger and longer generator potential.
   
   2. The increased generator potential is shown here as a larger depolarisation.
   3. The frequency of action potentials is proportional to the duration and intensity of the stimulus.
   4. Greater transmission along primary afferent.
   5. Increased release of neurotransmitters at the synapse with the second neuron of the afferent pathway.

Question 9

what is adaptation

Answer 9

• Adaptation - whether there is a decrease in sensitivity in the presence of a constant stimulus
can be phasic or tonic

Question 10

Explain phasic receptors

Answer 10

adapt quickly after detecting a change in stimulus strength
• Strongly when the stimulus begins but soon stop firing
• Only fire again when the stimulus turns off
• Referred as movement receptors / rate receptors and provide dynamic information about a stimulus

Question 11

Explain tonic receptors

Answer 11

do not adapt or adapt very slowly during duration of the stimulus
• Detect continuous stimulus and continue to transmit impulses to the brain as long as the stimulus is present
• Keep brain constantly informed of the status of the body
• Provide information about static qualities of a stimuli
§ Eg. Merkel cells slowly adapt allowing for sustained pressure and fine touch to be perceived.

Question 12

what is receptive field

Answer 12

region on the skin which causes activaion of a single sensory neuron when stimulated

Question 13

how is receptive field being tested

Answer 13

using 2-point discrimination test to test minimum distance at which two points are perceived as separate

Question 14

compare small receptive fields and large receptive fields

Answer 14

small receptive fields allow detection of finer detail and are important in precise perception while larger receptive fields allow detection over a wider area and present in body where precise perception is not important

Question 15

What is saltatory conduction

Answer 15

propagation of action potential along myelinated axons from one node of Ranvier to the next node, increasing conduction velocity of action potential

Question 16

What are the three types of primary afferents

Answer 16

A beta fibres are wide myelinated fibres and transmit fast signal of mechanical information to spinal cord
A delta fibres are medium myelinated fibres that transmit fast signal about pain and temperature
C-fibres are small unmyelinated afferents with slow conduction velocity about temperature, pain and itch information

Question 17

What is the difference between somatosensory system and our special senses (sight, hearing ,smell)

Answer 17

• Somatosensory receptors are located throughout the body instead of densely distributed to a specific site (e.g. eye, ear, nose).

Question 18

Describe the dorsal column pathway

Answer 18

• Carriesfine discriminative touchandvibrationsensations from the large diameter, fast conductingA-betafibres from the spinal cord to the somatosensory cortex.

1. There are some local connections with interneurons in the dorsal horn but the majority of theAβ fibresprimary afferent neurons enter the ascendingdorsal column pathway.

2. Primary afferent neurons make their first synapse with 2nd order neurons in themedulla.
	• 2nd order neuronsdecussate(cross the midline) in the caudal medulla and form the contralateralmedial lemniscuswhich then projects up through the brainstem to thethalamus.

3. These 2nd order axons then terminate in thethalamus.
	• Finally, there are 3rd order neurons from the thalamus which project to thesomatosensory cortexwhere the size of the somatotopic area is proportional to the density of sensory receptors in that body region which is also referred to as the somatosensory homunculus.

Question 19

Describe spinothalamic pathway

Answer 19

• information from smaller diameterA-deltaandunmyelinated C-fibrescarrying information aboutpainandtemperature.

1. Primary afferent axons terminate upon entering thespinal cord, they synapse in thedorsal hornof the grey matter.
2. 2nd order neuronsdecussate immediatelyin the spinal cord and form the contralateralspinothalamic tract. The 2nd order neurons terminate in thethalamus
3. 3rd order neurons from thethalamusproject to thesomatosensory cortexwhere the size of the somatotopic area is proportional to the density of sensory receptors in that body region which is also referred to as the somatosensory homunculus.

Question 20

What fibres are involved in transmitting pain signals

Answer 20

A-delta - medium diameter and myelinated
type 1 - respond to mechanical pain and mediate first acute response to sharp pinprick pain
type 2 - lower heat pain threshold and transmit first acute response to heat pain
only responsive to mechanical stimulation at very high intensities

C fibres - small diameter and unmyelinated
mediate dull, persistant or second pain

Question 21

Explain the signalling when a pain signal is detected

Answer 21

• primary afferent neurons synapse in the dorsal horn, releasing glutamate which binds to post-synaptic glutamate receptors (i.e. AMPA and NMDA receptors).
  * This causes a depolarisation of 2nd order projection neurons, which cross the midline and then enter ascending pathways to the brain, the spinothalamic tract (or antero-lateral system).
  
  • The first synapse in the pain pathway is open to lots of modulation by endogenous analgesic (pain-relieving) systems,

Question 22

explain the pathway to achieve analgesia

Answer 22

1. Myelinated A-beta fibres are activated.
   
   2. These signals flood the pathway and stimulate the substantia gelatinosa in the dorsal horn of the spinal cord.
   3. The gate swings closed.
   4. The C (small, nociceptive) fibre signals are stopped at the gate and the pain signals are not transmitted to the thalamus.
   5. Analgesia is achieved. (inability to feel pain)

Question 23

function of surspinal modulation of pain

Answer 23

• activated in response to a noxious stimulus and release monoamine neurotransmitters – noradrenaline and serotonin
  * regulate the overall amount of pain felt
  * Can contribute to development of chronic pain

Question 24

Describe the ascending pathway in sursprinal modulation of pain

Answer 24

• reaching the thalamus with nociceptive information, also reach the amygdala (and other parts of the limbic system), with the emotional component of pain
  * the unpleasant feeling, anxiety and fear that accompanies a noxious stimulus, including autonomic activation associated with fight-or-flight responses

Question 25

Describe the descending pathway in sursprinal modulation of pain

Answer 25

• show how emotional states (from the amygdala) and the noradrenergic and serotoninergic activation (from the PAG via centres in the pons and medulla) can affect the perception of pain, by modulating neurotransmission at the spinal synapses on pre- and post-synaptic terminals in the dorsal horn of the spinal cord, directly or via interneuronsreleasingendogenous opioids(such as enkephalins and endorphins) can also inhibit transmission at the dorsal horn synapses.

Question 26

What are the causes and example of nociceptive pain and neuropathic pain

Answer 26

nociceptive pain is due to continuous tissue injury causing peripheral sensitisation of * nociceptorsand examples are osteoarthritis, mechanical low back pain, post-operative pain

Neuropathic pain is caused b y a lesion or disease of the somatosensory nervous system.
Exmaple are diabetic neuropathy, radiculopathy (sciatica)

Question 27

What are the sensitization mechanisms

Answer 27

peripheral sensitization - primary hyperalgeisa which describes pain sensitivity that occurs directly in damaged tisues and central sensitization - secondary hyperalgeisa that describes pain sensitivity that occurs in surrounding undamaged tissues

Question 28

What happens during primary hyperalgesia

Answer 28

• increased responsiveness and reduced threshold of nociceptive neurons in the periphery to the stimulation of their receptive fields.
  
  • release of inflammatory mediators around the sensory nerve ending
    
    • results in the development of skin sensitivity
  • Sensitisation of nerve ending by inflammatory mediators reduces the threshold for activation by painful stimuli
    
    • causing increased pain from a stimulus that normally provokes pain.

Question 29

What happens during secondary hyperalgesia

Answer 29

• It is a form of synaptic plasticity which can result in normally innocuous stimuli becoming painful (a phenomenon calledallodynia) and painful stimuli become more painful, often in sites distant to the initial injury (secondary hyperalgesia),
  * Synaptic plasticityis the biological process by which specific patterns of synapticactivity result in changes insynapticstrength, which is thought to contribute to the development of pain hypersensitivity.

Question 30

what can be used to treat nociceptive chronic pain

Answer 30

non-steroidal anti-inflammatory drugs, and opioids

Question 31

what can be used to treat neuropathic chronic pain

Answer 31

antidepresants, and anticonvulsants

Question 32

action of Non-steroidal anti-inflammatory drugs (NSAIDs)

Answer 32

• reduce the peripheral sensitisation of nociceptors, by inhibiting the inflammatory response, specifically cycloxygenase, the enzyme that produces prostaglandins.

Question 33

action of opioids

Answer 33

• Activation of the receptors present both on the presynaptic terminals of primary afferent neurons and postsynaptically on the second order neuron,
  * inhibits nociceptive neurotransmission in spinal cord, and therefore causes analgesia

Question 34

Action of antidepressants and anticonvulsants

Answer 34

• Enhance the monoaminergic descending inhibition of nociceptive signalling in the dorsal horn, by inhibiting the reuptake of noradrenalin and serotonin
  * drugs of choice for neuropathic pain.