The Somatosensory System and Chronic Pain

Question 1

What is pathological pain?

Answer 1

When the somatosensory system, which provides information about the outside world (eg. pain as a warning signal to potentially/actually threatening stimuli), goes wrong, causing pathological and then chronic pain.

Question 2

What are sensory modalities?

Answer 2

Sensory modalities are types of sensory stimuli. Special senses have their own modalities (vision, hearing, olfaction, taste) & visceral sensation has interoceptors. The somatosensory modalities are touch (pressure, vibration, itch, tickle), temp, nociception, proprioception. They are detected by specialised receptors in skin, muscles, tendons that transmit info through specific anatomical pathways to the brain

Question 3

Name the different types of receptors

Answer 3

Mechanoreceptors - Touch, vibration, pressure
Thermoreceptors - Temperature
Nociceptor - Nociception

Question 4

Describe the general structure of a mechanoreceptor

Answer 4

They have nerve endings enclosed within layers of connective tissue called capsules

Question 5

What are proprioception receptors?

Answer 5

Muscle spindles (sense skeletal muscle stretch), Golgi organs (in tendons) and joint receptors

Question 6

What are thermoreceptors?

Answer 6

They are free sensory nerve endings in the skin. Specific temperatures activate a family of transient receptor potential channels.

Question 7

Describe the different types of thermoreceptors

Answer 7

TRPV1/2 are associated with noxious (potentially/actually harmful) heat - thermal nociceptors (>40C and capsaicin). TRPV2 higher than 1. TRPV3/4 are activated by warm (innocuous) temperatures. TPRA1 activated by <15C (painfully cold), TRPM8 is activated by cool temperatures and menthol.

Question 8

Describe the function of nociceptors

Answer 8

They also exist as free nerve endings in the skin. They are high threshold sensory detectors that respond to noxious stimuli.

Question 9

What are the different types of nociceptors?

Answer 9

Thermal (extreme temperature), mechanical (intense pressure), and polymodal (thermal, mechanical, chemical eg pH, immune chemicals, etc).

Question 10

Describe the process of sensory transduction

Answer 10

Cation channels in the membrane open in response to the stimulus. Stretch of membranes, or the force applied to connected extracellular proteins, or intracellular cytoskeletal components, activates mechanoreceptors. The stimulus intensity needs to reach the threshold of the voltage gated Na+ channels. TRP thermoreceptors are activated by temp changes

Question 11

What is sensory transduction?

Answer 11

How the stimulus is turned into an electrical signal

Question 12

How is an increased stimulus intensity able to be perceived as such?

Answer 12

A longer/stronger stimulus -> longer/stronger generator potential -> greater AP frequency -> more neurotransmitter release -> perceived stronger stimulus

Question 13

What is meant by phasic and tonic receptors?

Answer 13

Receptors are classified based on their adaption properties ie. do they decrease on increase in sensitivity in the presence of constant stimulus

Question 14

What is the property of a phasic receptor?

Answer 14

They adapt quickly after detecting a change in stimulus strength. They react strongly to the stimulus, but stop reacting soon after, and begin again when the stimulus is removed. They are movement/rate receptors and provide dynamic info about the stimulus, eg. Pacinian mechanoreceptor is excited by pressure and only transmits a signal again when the pressure is relieved

Question 15

What is the property of a tonic receptor?

Answer 15

They dont/very slowly adapt during the duration of a stimulus. As long as the stimulus is present, the continuously transmit impulses to the brain. They exist to keep the brain constantly informed of the status of the body. They provide info about static qualities of a stimulus eg. Merkel cells slowly adapt, allowing sustained pressure and fine touch to be perceived

Question 16

What is a receptive field?

Answer 16

A region of skin that, when stimulated, causes activation of a single sensory neuron. The two point discrimination test measures the size of a receptive field.

Question 17

How are receptive fields linked to sensitivity of skin?

Answer 17

Sensitive areas of skin have densely packed receptors, with small receptive fields to allow detection of fine detail over a small area eg. densely packed Meissner corpuscles and Merkel cells

Question 18

What are primary afferent fibres?

Answer 18

Sensory neuron fibres carrying info from the periphery to the CNS. They pass through the DRG (soma location) and enter the spinal cord

Question 19

How are primary afferent fibres classified?

Answer 19

AB fibres - wide diameter, myelinated, transmit fast, mainly mechnical info from skin
Adelta - medium diameter, myelinated, fast transmission, about pain and temp
C- small diameter, unmyelinated, slow, about temp, pain, itch

Question 20

What is the difference between the somatosensory system and the special senses?

Answer 20

Somatosensory receptors are located throughout the body, not densely distributed at a specific site.

Question 21

What sensations does the dorsal column pathway carry?

Answer 21

Fine discriminative touch, vibration from the spinal cord to the somatosensory cortex

Question 22

Describe the dorsal column pathway

Answer 22

Majority of AB primary afferents enter ascending dorsal column pathway, synapse with 2nd order neurons in medulla, which decussate here, forming contralateral medial lemniscus which projects through brainstem to thalamus. 2nd order neurons synapse with 3rd order neurons in thalamus and project to somatosensory cortex

Question 23

Which sensations does the spinothalamic pathway carry?

Answer 23

Pain and temperature

Question 24

Describe the spinothalamic pathway

Answer 24

Adelta and C fibres synapse in the dorsal horn grey matter with 2nd order neurons. These decussate immediately in the spinal cord to form the contralateral spinothalamic tract. These then synapse in the thalamus with 3rd order neurons which project to the somatosensory cortex

Question 25

What is pain?

Answer 25

A distressing feeling often caused by intense of damaging stimuli. Highly complex and subjective, involving sensory and emotional components

Question 26

What is nociception?

Answer 26

Nociception is the sensation consequent to potentially/actually damaging stimuli, detected by nociceptors. They send possible threat signals to the brain which it then interprets as pain

Question 27

Which mutation is responsible for congenital insensitivity to pain?

Answer 27

Pain is important in keeping us alive. SCN9A mutation -> insensitivity

Question 28

What is the role of Adelta fibres in the transmission of pain?

Answer 28

They mediate sharp, intense pain. Type I respond to mechanical pain (pinprick), and mediate the first acute response to sharp pain. Activated by sustained temperatures over 50C. Type II have a much lower heat pain threshold and transmit the first acute response to heat pain. They’re only responsive to mechanical stimuli at high intensity

Question 29

What is the role of C fibres in the transmission of pain?

Answer 29

They transmit dull, persistent, second pain. They are polymodal, meaning they respond to noxious thermal, chemical, mechanical stimuli

Question 30

How is pain modulated in the spinal cord?

Answer 30

AB fibres from mechanoreceptors directly and indirectly inhibit C fibres. Stimulation of AB fibres by electricity or rubbing floods the pathway with signals and stimulates the substantia gelatinosa in the dorsal horn. This shuts a gate in the thalamus, which means that the C fibres are stopped, and the signal cannot get to the thalamus. Dampening the pain at the synapse means there’s less overall output to the brain.

Question 31

How is pain modulated supraspinally?

Answer 31

Higher centres in the CNS can modulate pain processing in the spinal cord. The pathways are activated in response to noxious stimuli, and involve the release of monoamine neurotransmitters (noradrenaline and serotonin) in the spinal cord

Question 32

What are the physiological and pathological roles of the supraspinal pain modulation pathways?

Answer 32

Physiologically, the pathways lead to reduced amounts of pain felt. Pathologically, they lead to chronic pain (reduced inhibiton/increased excitation). These pathways are the target of analgesic drugs

Question 33

What is the role of the ascending pathways in supraspinal pain modulation?

Answer 33

They go to the thalamus and also the amygdala and other parts of the limbic system with the emotional component of pain: fear, anxiety, along with autonomic activation associated with fight or flight

Question 34

What is the role of the descending pathways in supraspinal pain modulation?

Answer 34

Modulates neurotransmission directly or indirectly via interneurons releasing endogenous opioids. Activates PAG via serontonins or noradrenaline

Question 35

Which other ways can pain be modulated?

Answer 35

Electrical stimulation of PAG -> profound and selective analgesia, which can be mimicked by electroacupuncture or hyponosis. Hypnosis deactivates the anterior cingulate cortex -> no pain

Question 36

What is chronic pain?

Answer 36

Pain that persists beyond acute pain, typically lasting over 6 months.

Question 37

How can chronic pain be classified?

Answer 37

According to pathophysiology (nociceptive, neuropathic), etiology (post-op, cancer), affected area (lower back, headache).

Question 38

What is nociceptive pain?

Answer 38

Pain due to continuous tissue injury, which leads to peripheral sensitisation of peripheral nociceptors. Aching, tender, localised pain, which gets better over time

Question 39

What is neuropathic pain?

Answer 39

Pain due to a somatosensory lesion/disease. Central sensitisation, stabbing, sharp, pins and needles, can spread (diffuse). Serves no physiological purpose, entirely pathological

Question 40

What is sensitisation?

Answer 40

Following injury, the sensitivity of an area increases greatly. Various mechanisms can increase pain perception

Question 41

Describe the mechanism of peripheral sensitisation

Answer 41

It is increased responsiveness and reduced threshold of nociceptive neurons in the periphery. The release of inflammatory mediators around the sensory nerve endings results in skin sensitivity. This reduces the pain activation threshold, which leads to increased pain. AKA primary hyperalgesia

Question 42

Describe the mechanism of central sensitisation

Answer 42

This is increased responsiveness of nociceptive neurons in the CNS. It is due to a form of synaptic plasticity which leads to normally innocuous stimuli becoming painful (allodynia) or painful stimuli becoming even more painful, often in sites distant to the initial injury (secondary hyperalgesia)

Question 43

What is synaptic plasticity?

Answer 43

When specific patterns of activity lead to changes in synaptic strength

Question 44

How can non-steroidal anti inflammatory drugs be used to treat chronic pain?

Answer 44

Works for nociceptive pain but not neuropathic. Reduces the peripheral sensitisation of nociceptors by inhibiting the inflammatory response, specifically COX (produces prostaglandins). eg. Aspirin, ibuprofen, paracetamol

Question 45

How can opioids be used to treat chronic pain?

Answer 45

Activates opium receptors on presynaptic terminals of primary afferent neurons and post synaptic terminals of 2nd order neurons to inhibit nociceptive neurotransmission in spinal cord. Doesn’t work for neuropathic because nerve injury leads to downregulation of opioid drugs

Question 46

How can antidepressants and anticonvulsants be used to treat chronic pain?

Answer 46

They enhance monoaminergic (noradrenaline and serotonin) descending inhibition of nociceptive signalling in dorsal horn by inhibiting serotoning and noradrenaline reuptake. Used for neuropathic pain