Lecture 11: Pain

Question 1

What is pain?

Answer 1

an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage

Question 2

What is nociceptive pain?

Answer 2

caused by noxious stimuli (heat, cold, intense mechanical force, chemical irritants)

adaptive, high-threshold pain, early warning system (protective)

“good” pain tells the brain to stop walking on a broken foot

Question 3

What is pathological pain?

Answer 3

neural lesion

positive and negative symptoms

spontaneous pain, pain hypersensitivity

no adaptive benefit to the pain

maladaptive, low-threshold pain

Question 4

What is allodynia?

Answer 4

pain due to a stimulus which normally does not cause pain

Question 5

What is neuropathy?

Answer 5

disturbance in function or pathologic change in a nerve

Question 6

What is central pain?

Answer 6

pain caused by a primary lesion or dysfunction in the CNS

Question 7

What is neuropathic pain?

Answer 7

pain caused by a primary lesion or dysfunction in the NS

Question 8

What is dysesthesia?

Answer 8

unpleasant abnormal sensation

Question 9

What is paresthesia?

Answer 9

abnormal sensation, whether spontaneous or evoked

Question 10

What is hyperesthesia?

Answer 10

increased sensitivity to stimulation

Question 11

What is hypoesthesia?

Answer 11

decreased sensitivity to stimulation

Question 12

What is the specificity theory of pain?

Answer 12

a specific pain system carries messages from pain receptors in the skin to a pian centre in the brain

originally formulated by Descartes in 1664

suggests a direct, invariant relationship between a psychological sensory dimension and a physical stimulus

Question 13

What is the gate control theory of pain?

Answer 13

pain can be modulated

a “gate” within the spinal cord be opened or closed

G cell = gated cell
T cell = transmission cell

TENS machines work on the gate

Question 14

What are the “large light” primary sensory neurons?

Answer 14

A-alpha and A-beta

discriminative touch

proprioception

non-painful things

Question 15

What are the “small dark” primary sensory neurons?

Answer 15

A-delta and C

pain and temperature

nociceptor

C is true pain receptor

Question 16

What are the properties of A-alpha and A-beta fibres?

Answer 16

myelinated
large diameter
proprioception, light touch

Question 17

What are the properties of A-delta fibres?

Answer 17

lightly myelinated
medium diameter
nociception (mechanical, thermal, chemical)

Question 18

What are the properties of C fibres?

Answer 18

unmyelinated
small diameter
innocuous temperature, itch
nociception (mechanical, thermal, chemical)

Question 19

What are the central projections in the primary sensory neurons?

Answer 19

A-beta fibers project to deep lamina (III, IV, V)

A-delta to superficial (1, II) and deep (V)

C nociceptors to superficial

interneurons connect II to WDR (wide dynamic range)

lamina I neurons have projections (crossed) to STT

lamina II interneurons connect with WDR in Lamina V
WDR axons contribute to STT (spinothalamic tract)

Question 20

What is sensitization and plasticity in pain pathways?

Answer 20

pain processing is very dynamic

signals may be “amplified” (hyperalgesia) or responses to previously innocuous stimuli may emerge (allodynia)

can serve a protective function

“sensitization” can occur at a variety of levels; peripherally or centrally

numerous mechanisms are involved

Question 21

What is peripheral sensitization in the pian pathways?

Answer 21

tissue damage triggers inflammatory soup to be released

most mediators in the inflammatory soup don’t bind to a receptor, instead they modify and send secondary messages

second messengers modify ion channels by phosphorylation

ion channel may open at lower voltage or remain open longer

boost excitability/activity

reduced threshold for activation, increased output to a given stimulus

Question 22

What is normal transmission compared to central sensitization?

Answer 22

“normal” EAA release

activation of AMPARs

NMDARs “silent” due to Mg2+ block

Question 23

What does transmission look like in central sensitization?

Answer 23

“enhanced” EAA release, neuropeptides

recruitment of NMDARs

Ca2+ entry: phosphorylation (acute)

Ca2+ entry: gene transcription (long term)

reduced threshold, increased output (more action potentials)

Question 24

What are the three dimensions of pain?

Answer 24

sensory-discriminative

affective-motivational

cognitive-evaluative

Question 25

What is the sensory-discriminative dimension of pain?

Answer 25

location
intensity
duration

Question 26

What is the affective-motivational dimension of pain?

Answer 26

unpleasantness
“quality”
“burning” or “shock-like” pain

Question 27

What is the cognitive-evaluative dimension of pain?

Answer 27

attention
anticipation
memory

Question 28

What is the brain’s response to pain?

Answer 28

seeing pain as something bigger than just stimulus response

brain’s response to pain is dynamic

the context of a situation can dictate how the brain responds to a painful stimulus

“intensity coding” regions vs. “attentional networks” can be engaged differently

activity goes beyond the standard “sensory” centres

pain as a three dimensional, sensory experience

“affective” and cognitive centres are responsive even in the absence of sensory input

Question 29

How do you treat peripheral pain?

Answer 29

local anesthetic block sodium channels and prevent action potentials (Lidocaine)

NSAIDS block PGE2 production, block production of mediators in inflammatory soup

inhibit second messenger pathways to prevent sensitization (opioids, cannabinoids)

Question 30

How do you treat central pain?

Answer 30

prevent signals from PNS, no detection

less impulses to the brain

Question 31

How are antidepressants used to treat pain?

Answer 31

increase levels of serotonin and noradrenaline

antidepressants can elevate 5HT levels

5HT can inhibit spinal neurons

Question 32

What are SNRIs and neuropathic pain?

Answer 32

serotonin-norepinephrine reuptake inhibitors

elevate level of 5HT and NE in the synaptic cleft

duloxetine is approved for neuropathic pain and fibromyalgia

Question 33

How is the processing pain dynamic?

Answer 33

pain signals can be “amplified”

sensitization can occur at the peripheral nerve terminals or within the CNS

peripheral sensitization “inflammatory soup” can trigger intracellular cascades that lead to modification of ion channels

central sensitization - enhanced input can recruit NMDA receptors

overall: decreased threshold for activation, increased output to a stimulus

Question 34

How is pain treated?

Answer 34

block production of inflammatory mediators to prevent the sensitization “cascade”

block ion channels responsible for generating the action potential in nociceptors

enhance “inhibition” within the nociceptor to prevent sensitization