Pain

Question 1

why is pain needed?

Answer 1

• to be aware of minor injuries
• unless carefully managed, injuries could become infected leading to diseases such as leprosy
• people who are congenitally insensitive may be unaware of injuries and could end up causing more damage

pain is essential for survival

Question 2

what illnesses can cause loss of pain sensation?

Answer 2

• leprosy
• diabetes mellitus

due to nerve damage

Question 3

how does pain differ from classical senses such as vision?

Answer 3

• it is both a discriminative sensation and a graded motivation (behavioural drive)

Question 4

what strange symptoms can pain cause?

Answer 4

• allodynia: sensitisation to normally innocuous stimuli
• hyperpathia: hysterical responses to small pain
• temporal augmentation
• after-sensations
• emotional variability

Question 5

what is convergence theory?

Answer 5

• suggests that pain is an integrated, plastic state represented by a pattern of convergent somatosensory activity within a neuromatrix

Question 6

what is specificity theory?

Answer 6

• pain is a distinct sensation, detected and transmitted by specific receptors and pathways to distinct pain areas of the brain

Question 7

what are pain receptors?

Answer 7

free nerve endings called nociceptors

Question 8

how are nociceptors classified?

Answer 8

• according to the activating stimulus, the fibre type and the conduction velocity

Question 9

what are the A-delta nociceptor fibres?

Answer 9

• lightly myelinated
• fast: 20m/s
• mechano-sensitive and mechanothermal-sensitive

Question 10

what are the C nociceptor fibres?

Answer 10

• unmyelinated
• slow: 2m/s
• polymodal: mechanical, thermal and chemical sensitive

Question 11

what are nociceptors?

Answer 11

• a subset of afferents with free nerve endings that respond specifically to pain

Question 12

how can mechanothermal-sensitive nociceptors be identified to specifically respond to pain by heat?

Answer 12

• in heat responses, afferents whose activity correlates with pain perception can be identified
• thermoreceptor activation has already saturated before pain is perceived
• this means pain is not due to the ramping up of normal receptors, and is instead perceived by separate nociceptors

Question 13

what are the two categories of pain fibres?

Answer 13

1. Fast/first pain: sharp and immediate
   - mimicked by stimulation of A-delta fibres
2. Slow/second pain: delayed, diffuse and longer-lasting
   - mimicked by stimulation of C fibres

Question 14

how can specificity of nociceptors be determined compared to other fibres?

Answer 14

• stimulation of A-alpha (proprioceptive) and A-beta (mechanoreceptive) fibres NEVER elicits pain sensation

therefore there is a distinct set of A-delta and C nociceptor fibres that are specifically used in pain detection

Question 15

what are molecular pain receptors?

Answer 15

• specific molecular receptors associated with nociceptor nerve endings are activated by heat
• capsaicin receptor (TRPV1) is activated in nociceptive A-delta and C fibres at 45C, and capsaicin which is the active component in chillies
• other molecular receptors are activated in A-dela fibres at higher thresholds (52C)

these molecular receptors are specifically heat detection machines

Question 16

how can nociceptors also detect chemicals?

Answer 16

• capsaicin from chillies mimics endogenous vanilloids that are released by stressed tissues
• therefore nociceptors can detect the release of chemicals from stressed cells

Question 17

what are the 2 central pain pathways?

Answer 17

1. sensory discriminative pathway
   - signals location, intensity and type of stimulus
   - involves the spinothalamic tract/anterolateral system
2. Affective-motivational pathway
   - signals unpleasantness and enables autonomic activation of fight or flight response

Question 18

how do spinothalamic projections preserve topology?

Answer 18

measuring the activity of the somatosensory cortex indicates:

1. this region responds to painful stimuli which correlates to pain intensity
2. this is spatially mapped

Question 19

how is pain cortically represented?

Answer 19

• MRI of cortical activation of C fibres (pain stimuli) and A-beta fibres (mechanical stimuli) show that pain stimuli activate the same region in the somatosensory cortex as non-painful mechanical stimulation applied to the same area
• pain however has a distinct response that includes other regions

Question 20

what other regions in the cortex does pain activate?

Answer 20

1. insula
2. cingulate cortex

• both regions are connected to the limbic system and are involved in emotional responses
• part of the affective-motivational response to pain

Question 21

what is the affective-motivational pathway?

Answer 21

• no topographic mapping
• neurons in parabrachial nucleus respond to painful stimuli from anywhere on skin
• input into limbic and hypothalamic systems
• activity in cingulate cortex corresponds with unpleasant feeling of pain
• about emotion, not intensity (discriminative pathway)

Question 22

what conclusions have been made that pain perception is aligned with specificity theory?

Answer 22

1. both cellular and molecular receptors that respond specifically to pain
   - A-delta fibres, C fibres and TRPV1
2. there are specific pathways that convey pain messages
   - discriminative and affective-motivational
3. regions in the CNS are specifically activated in response to pain
   - limbic system, insula, cingulate cortex and somatosensory cortex

Question 23

which phenomena of pain do not fit with the specificity theory?

Answer 23

1. pain perceived is not always proportional to stimulus intensity
2. pain is modulated by other stimuli e.g. acupuncture
3. phantom limbs
4. referral of pain from viscera to skin
5. placebo

Question 24

what is hyperalgesia?

Answer 24

increased response to a painful stimulus

• hypersensitivity of damaged skin to a normally tolerable painful stimulus e.g. skin prick
• result of lowered nociceptor thresholds which heightens pain response

Question 25

what is allodynia?

Answer 25

painful response to a normally innocuous stimulus | - painful sensitivity of sunburnt skin to gentle mechanical stimulus or mild temperature

Question 26

what is the inflammatory response?

Answer 26

- tissue damage releases inflammatory substances which affect nerve function, recruit mast cells and neutrophils, and increase blood flow - bradykinin directly affects function of nociceptive molecular receptors (TRPV1) - prostaglandins lower threshold for AP generation

Question 27

how do aspirin and ibuprofen affect the inflammatory response?

Answer 27

- aspirin and ibuprofen are analgesics (painkillers) | - they act on cyclooxygenase (COX), an enzyme important in prostaglandin biosynthesis

Question 28

what is central sensitisation?

Answer 28

- result of activity-dependent local release of prostaglandins from nociceptive dorsal horn neurons - prostaglandins lower thresholds for AP generation for neurons relaying nociceptive info, leading to hyperalgesia - these neurons become sensitive to non-nociceptive inputs, so innocuous stimuli can be perceived as painful - allodynia

Question 29

what is hyperpathia?

Answer 29

- results when there is fibre loss/damage (centrally or peripherally) that causes raising of detective threshold - when the detection threshold is exceeded, the excitability is much greater, causing explosive pain

Question 30

when can central sensitisation also occur (not inflammatory response)?

Answer 30

- when central pathways are damaged - e.g. in diabetes mellitus, shingles, multiple sclerosis or after stroke - neuropathic pain can be experienced after limb amputation

Question 31

what is phantom limb pain?

Answer 31

- patients have illusion that the limb that has been amputated is still present - indicates that central representation of the body persists in the absence of peripheral input - children born without limbs can have phantoms, so the map may be preformed - amputees experience phantoms, suggesting pain may be a representation of what we expect it to be

Question 32

what is referred pain?

Answer 32

- pain due to damage of viscera is perceived as coming from certain locations on skin - e.g. heart attack is preceded by pain in left arm - reflects convergence of visceral afferents onto same pathways as cutaneous afferents in CNS

Question 33

how is pain centrally modulated?

Answer 33

- pain perception varies according to context - mechanisms exist, voluntary or involuntary, to over come severe pain - e.g. soldiers with severe wounds experienced no pain - placebo effect of relieving pain

Question 34

what is the molecular mechanism in modulating pain?

Answer 34

- stimulation of periaqueductal grey activates brainstem nuclei that modulate dorsal horn activity - descending inputs from the dorsal horn activate enkephalin - enkephalin releases interneurons which presynaptically inhibit nociceptive fibres

Question 35

what are enkephalins?

Answer 35

- members of a family of endogenous opioid peptides that include endorphins and dynorphins - they release interneurons which presynaptically inhibit nociceptive fibres

Question 36

how can pain modulation occur locally?

Answer 36

- rubbing on an injury causes A-beta fibres (mechanoreceptors) to inhibit nociceptive C fibre inputs into spinal cord - known as gating of pain - pain perception is the result of integration of convergent sensory info

Question 37

how do we know that pain is not another somatic sense?

Answer 37

Nociceptive information is carried to areas of the limbic system whose activity correlates with the ‘experience’ that pain is unpleasant

Question 38

why does Hyperpathia differ from hyperalgesia and allodynia?

Answer 38

it involves a reduction in sensitivity due to a raising of the pain detection threshold