Physiology of pain

Question 1

What are nociceptors?

Answer 1

• somatosensory primary afferents
• their cell body is in the dorsal root ganglion
• its axon makes connections to dorsal horn
• nociceptor axons dont project to brainstem
• peripheral nerve endings are the sensory receptors

Question 2

What are the two classes of nociceptors?

Answer 2

• immediate sharp pain = A-delta fibres

- delayed, aching pain = c-fibres

Question 3

A-delta fibres

Answer 3

• thin, myelinated axon
• respond to mechanical trauma and noxious heat
• synapse onto spinal cord and produce first sharp stab of pain when injured
• NT = glutamate
• signal passes from dorsal horn to anterolateral spinal tract and up to the brain

Question 4

C-fibres

Answer 4

• thin, unmyelinated axons - propagate axons slower
• synapse in dorsal horn
• respond to inflammation, mechanical trauma, noxious heat/cold
• NT = glutamate, Sub P and others

Question 5

How do nociceptors respond to inflammation?

Answer 5

• ruptured cells release K+ and H+ - causes inflammation and release of mediators - depolarise the nerve endings of local C fibres - propagates along rest of fibre
• Use same inflammatory mediators as NTs (e.g. Sub P)
• gives increased sensitivity to future inflammatory mediators - positive feedback

Question 6

How do nociceptors contribute to inflammation?

Answer 6

• signal also spreads along the rest of the network of C fibres nearby it and along the infamed area - produces swelling and redness around it
• more release of histamine and sub P generating inflammation and giving hypersensitised tissue - causes pain from slight pressure around injured area - rim of protection

Question 7

How does pain allow us to live a healthy life?

Answer 7

• protective reflexes (withdrawal reflex)
• learning and avoidance
• remedial actions
• immobilsation after injured joint

Question 8

Main somatosensory pathway

Answer 8

• main axon to dorsal column nuclei
• ascends in medial lemniscus
• secondary afferent coming from synapse in Ventral posterior nucleus
• ascends in internal capsule
• to tertiary afferent which terminates in sensory strip

Question 9

Lateral Pain pathway

Answer 9

• nociceptors terminate in dorsal horn of spinal cord
• secondary afferent crosses midline in spinal cord
• goes straight up to the thalamus from dorsal root bypassing the medulla
• synapses at VP nucleus
• ascends to sensory strip via internal capsule
• localises pain

Question 10

Referred pain

Answer 10

• no area for heart of lungs on homunculus because of referred pain
• afferent come up the spinal cord and go to appropriate parts of homunculus
• If you have a heart attack, it will activate pain afferents from the heart, which will activate the same area of the homunculus as the left arm

Question 11

Medial pain pathway

Answer 11

• nociceptors run up anterolateral tract, terminating in brainstem at modulatory and autonomic control centres
• Here they can activate sympathetic areas
• make connections with non-specifc thalamic nuclei
• go to anterior cingulate cortex tp limbic structures such as hypothalamus and amygdala
• also insular cortex to control homeostasis
• stimulation causes unpleasant feelings that are hard to localise and describe

Question 12

Lateral vs medial

Answer 12

• Lateral lesion - can feel pain, but cannot localise it

- medial lesion - can localise pain, but dont care about it

Question 13

Why can pain sometimes not be in proportion to nociceptor activation?

Answer 13

• stress-induced analgesia = don’t feel the pain because the high stress is stopping you from feeling it
• anxiety-induced hyperalgesia = more likely to find something painful if they are anxious about it beforehand

Question 14

What areas of the brain are involved in analgesia?

Answer 14

• RV medulla - primarily serotonergic cells in Raphe magnus. effects can be facilitatory as well as inhibitory
• pontine tegmentum - especially NAergic cells of locus coeruleus (but also some Ad and ACh)
• morphine acts at Orbitofrontal cortex, PAG and inhibits nociceptors - suppresses pain by activating or mimicking receptive pathways
• CBT aims to tricks these natural analgesics into action

Question 15

pathological pain

Answer 15

• pain can result from pathological activation of nociceptors
• spontaneous pain (spontaneous nociceptor activity)
• Hyperalgesia - increased activity in sensitised nociceptors and pathways
• Allodynia - pain produced by non-noxious stimuli
• PAIN PERSISTS AFTER HEALING

Question 16

Causes of pathological pain

Answer 16

• microinjury to nociceptor itself - enhanced by upregulation of inflammatory signalling mechanisms and alterations to VGNa channels
• abnormal processing
• triggered by injury, but becomes independent of tissue damage (neurogenic)

Question 17

Spinal cord inhibition controls activity in pain pathways

Answer 17

• pain afferents terminate in I,II and V
• Superficial layers only respond to damaging stimuli
• lower layers will respond at low freq. to ordinary touch, but high freq. when they get nociceptor input (interpreted as injury at high freq.)
• transmission is controlled by inhibitory interneurons, which are controlled by descending pathways

Question 18

Long-term potentiation can contribute to chronic pain states

Answer 18

• have C-fibre and its secondary afferent
• activate fibre at regular intervals, then record their activity and the activation of the fibre they synapse on to
• in chronic pain,only need a very brief stimulation to cause doublee the freq of response in the synapsed cell
• triggered by neuropathy and nerve trauma

Question 19

Chronic pain

Answer 19

• often associated with depression and treatment with antidepressants can reduce pain by improving mood and coping ability - also increases transmission of descending anti-nociceptive pathways
• Treatment with BZDs (anxiolytics), also enhance inhibition in the dorsal horn, reducing pain
• treatment with anticonvulsants can block enhanced activity due to abnormal VGNa channels, plus reduce NT release at potentiated synapses