Lecture 9: Pain Flashcards
(52 cards)
1
Q
What are nociceptors?
A
- Pain and temperature afferent fibers
- Come from cell bodies in dorsal root ganglia
- Send one axon to periphery and other to spinal cord
- Identified by axon
- Pseudounipolar with free nerve endings
2
Q
Can thermoreceptors and nociceptors be active at the same time?
A
- Yes
- Thermoreceptors are active, then reach threshold and are stable
- Nociceptors become activated after a heat threshold (43-45C) is reached
3
Q
How does the speed of pain afferents compare to that of cutaneous mechanoreceptors? Why?
A
- Relatively slow
- Lighly myelinated or unmyelinated
4
Q
What are the 2 phases of pain sensation?
A
- First pain
- Second pain
5
Q
Describe first pain. Which nociceptors are activated?
A
- Sharp, initial pain
- Adelta fiber nociceptors
6
Q
Describe second pain. Which nociceptors are activated?
A
- Delayed, duller/burning pain, longer duration
- C fiber nociceptors
7
Q
Describe Type I Adelta nociceptors
A
- Low thresholds for dangerous levels of mechanical (twist/tear) and chemical stimulation
- High heat thresholds
8
Q
Describe Type II Adelta nociceptors
A
- Low heat thresholds
- High mechanical/chemical thresholds
9
Q
Describe C fiber nociceptors
A
- Most are polymodal (responsive to all forms of nociceptive stimuli)
10
Q
What happens when Adelta fibers are blocked?
A
- First pain does not occur
- Second pain still does
11
Q
What happens when C fiber axons are blocked?
A
- First pain occurs
- Second pain does not
12
Q
What is involved in the transduction/transmission of thermal pain stimuli? Is it excitatory or inhibitory?
A
- Excitatory
- Transient Receptor Potential (TRP) Vanilloid Receptor (TRPV1) is a Na+/Ca2+ ion channel which is closed at rest
- Activated by noxious heat (+43C, acid, capsaicin and anandamide)
- Endovanilloids activate these receptors
13
Q
What are endovanilloids?
A
- Produced by peripheral tissues in response to injury
- May contribute to nociceptive response to injury
14
Q
What receptors are responsible for mechanical/chemical pain stimuli?
A
- TRPA1
- Chemical irritants - mustard/garlic/tear gas/vehicle exhaust/cigarretes
- ASIC3
- Muscle/cardiac pain - pH changes associated with ischemia
15
Q
What must occur in order to transmit pain information to the spinal cord? What sodium channels are activated?
A
- AP must be triggered in distal nociceptors
- Nav1.7 sodium channel subtype
- Nav1.8 sodium channel subtype
16
Q
Describe what occurs as a result of a loss of function of the Nav1.7 sodium channel or hyperactivation of this sodium channel.
A
- Loss of function (mutation in SCN9A in humans) = inability to detect noxious stimuli
- Hyperactive = pain disorder causing intense burning sensation
17
Q
Describe the Nav1.8 sodium channel subtype.
A
- Expressed by C-fibers
- Transmission of noxious mechanical/thermal signals
18
Q
What is the difference in pain pathways in comparison to mechanoreceptive pathways?
A
- Pain pathways ascend spinal cord contralaterally
- Mechanoreceptive pathways ascend ipsilaterally and cross over at medulla
- Pain pathways are distinct from mechanosensory pathways
19
Q
How do first order nociceptive afferents travel in the anterolateral system?
A
- Sent from cell bodies in dorsal root ganglia
- Terminate in dorsal horn of spinal cord
- Branch across 1-2 spinal cord segments in Lissauer’s tract
- Penetrate into dorsal horn gray matter
- Connect to 2nd order in dorsal horn
20
Q
How do second order nociceptive afferents travel in the anterolateral system?
A
- Contacted by first order in Rexed’s laminae I, II, and V
- C-fibers terminate in Rexed’s laminae I and II
- Adelta fibers terminate in laminae I and V
- Those in I and V send axons across midline and ascend through anterolateral tract to brainstem/thalamic targets
21
Q
What results from a unilateral lesion in the left side of the spinal cord?
A
- Left: mechanosensory signals cannot ascend so left side experiences deficits in sensations to touch/pressure/proprioception
- Right: pain signals can no longer ascend, so right side experiences deficits in pain/temperature sensations
- DISSOCIATED SENSORY LOSS
22
Q
What is sensory-discriminative pain?
A
- First pain
- Learn that pain exists
- Location/intensity/quality of pain
- Information is relayed through ventral posterior lateral (VPL) nucleus of thalamus to neurons in SI and SII
- Distinct pathways so nociceptive info remains distinct
23
Q
What is affective-motivational pain?
A
- Second pain
- Context/what to do next
- Fear/anxiety
- Autonomic (sympathetic NS) activation (Fight or flight) associated with noxious stimulus
- More complex as axons project to a number of regions (ex. reticular formation, periaqueductal gray, superior colliculus, parabrachial nucleus, medial thalamic nuclei)
- In turn project to other regions (hypothalamus, amygdala, anterior cingulate cortex and insula)
24
Q
What role does the periaqueductal gray play in pain?
A
- Descending regulation of pain processing in midbrain
- Top-down processing
- Endogenous opioids
25
What role does the hypothalamus play in pain?
- Sympathetic NS response
26
What role does the amygdala play in pain?
- Fear processing
| - Learning how to avoid
27
What role does the anterior cingulate cortex play in pain?
- executive regulation of autonomic systems
28
What role does the insula play in pain?
- Integrated body state
29
Where do the pathways for noxious and thermal stimulation of face originate?
- Trigeminal ganglion
| - Ganglia of facial, glossopharyngeal, vagus cranial nerves
30
How do first-order fibers travel in face pain/temperature pathways?
- Enter pons
- Descend to medulla
- Connect with second-order in trigeminal nucleus
31
How do second-order neurons travel in face pain/temperature pathways?
- Cross midline
| - Ascend to project to various regions
32
How are projections grouped in face pain/temperature pathways?
- Based on sensory-discriminative pain and affective-motivational pain
- Reaching many of the same regions
33
What are 4 other things that the anterolateral system mediates?
- Tactile information
- Innocuous temperatures
- Itching
- Laminae layer 1 neurons
34
Describe how the anterolateral system affects tactile information.
- C fibers can maintain crude tactile sensation
- Non-discriminative touch
- Lacks fine spatial resolution that can be provided by dorsal column system
35
Describe how the anterolateral system affects innocuous temperatures.
- Non-painful thermal changes
- TRPV3 and TRPV4 detect warm temperatures
- TRPM8 detects cold temperatures
36
Describe how the anterolateral system affects itching.
- Pruriceptors
- Subset of C-fibers
- Can also respond to pain
37
Describe how the anterolateral system affects laminae layer 1 neurons.
- Sensory input for interoception (largely regulated by insula)
- Represents physiological condition of the body (maintaining homeostasis through hypothalamus)
38
What is sensitization?
Signal received more strongly
39
What is sensitization of pain called? What does it consist of?
- Hyperalgesia
- Following tissue damage, stimuli in that area would normally be perceived as only slightly painful are perceived as significantly more painful
- E.g. sunburn is more sensitive to temperature
40
How does peripheral sensitization occur?
- Interaction b/n nociceptors and other inflammatory substances released after tissue damage
- Nociceptors release certain peptides/neurotransmitters in response to damage
- Other non-neuronal cells (e.g. mast cells, platelets, macrophages) also release various other substances in response to tissue damage, most of which interact with nociceptive fibers augmenting their response, making them more sensitive
41
What is the purpose of peripheral sensitization?
- Helps protect injured area from further damage
- Promotes healing/prevents infection due to increased blood flow in that area, migration of white blood cells to that area, and production of substances that reduce inflammation
42
What is central sensitization?
- Excitability of dorsal horn neurons increases following high activity levels in nociceptive afferents
- Signals previously too weak become sufficient to trigger APs
- Allodynia
- Thought to involve LTP-like enhancement (alter architecture of neurons) of PSPs
43
What is allodynia?
AKA neuropathic pain
- Induction of pain by a normally innocuous stimulus
- Ex. clothing touching your body
44
What will happen to sensitization after healing?
- Normally declines
| - Returns to pre-injury levels
45
What is neuropathic pain?
- Chronic/intense pain experiences frequently seen in chronic conditions (ex. diabetes, AIDS, MS)
- Difficult to treat with analgesics
- Spontaneous occurrence (phantom limb) or by mild stimulus (clothes)
46
What is descending control of pain perception?
- discrepancy b/n objective reality and subjective response to pain sensation
- Perception of pain dependent on the context (ex. soldiers vs. job loss)
- Suggests pain perception is subject to central modulation
47
What is the placebo effect?
- A physiological response following the administration of a pharmacologically inert treatment
- Sensitive to suggestion
- Ex. postoperative pain
- Pain relief after saline
- Blocking opioid receptors blocks placebo effect
48
Stimulation of which region of the midbrain has been found to produce pain relief?
- Periaqueductal gray
49
What is involved in descending control of pain perception?
- Activation of descending pathways that modulate pain, projecting to dorsal horn
- Activation of PAG has been found to produce analgesia and inhibit activity of nociceptive projection neurons
- Other regions include parabrachial nucleus, dorsal raphe, locus coeruleus, reticular formation
- Provide balance b/n facilitatory and inhibitory influences that determines efficacy of nociceptive transmission
50
What is the gate theory of pain modulation?
- Nociceptive information transmission can be modulated by local interactions b/n mechanoreceptive afferents and neural circuits in dorsal horn
- E.g. stub toe and natural reaction is to rub to relieve pain (mechanoreceptors being activated by rubbing project to dorsal horn and activate local circuit neurons that inhibit transmission of nociceptive signals)
51
What role do endogenous opioids play in pain modulation?
- Descending projections release encephalin onto local circuit neurons, inhibiting ntx release from nociceptive afferents
- Reduces second order neuron activity (analgesic effect)
52
What role do endocannabinoids play in pain modulation?
- Can also modulate pain
- Analgesic effect of stimulating periaqueductal gray blocked by adminstering cannabinoid receptor antagonist
- Noxious stimuli exposure increases endocannabinoid levels in periaqueductal gray
