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Pharmacy > 301 Pain > Flashcards

301 Pain Flashcards

1
Q

Describe the pain pathway and relevant neurotransmitters

A

Stimulus: Noxious input activates C-fibers
Releases mediators (e.g., BK, 5-HT, PGs), NGF, and neuropeptides (SP, CGRP)
Excites neurons that carry pain signals to the brain
Enkephalins and GABA further inhibit pain transmission
Key Neurotransmitters: 5-HT, NA, enkephalins, GABA

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2
Q

What do opioids do in the pain pathway?

A

Endogenous/exogenous opioids inhibit pain signals

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3
Q

What happens in descending pain pathway?

A

Serotonin (5-HT) and noradrenaline (NA) reduce pain perception

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4
Q

Nociceptor structure

A

Cell body with cross section of spinal cord including peripheral terminal (somatic, visceral) and central terminals (spinal cord dorsal horn, brainstem)

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5
Q

Types of fibers in the peripheral nerves

A

Aδ Fibers: thin, myelinated fibers; transmit sharp, fast pain (acute pain)
C Fibers: unmyelinated fibers, carry dull, slow pain (chronic pain)
Aβ Fibers: thick, myelinated fibers, transmit touch & pressure, can inhibit pain when stimulated (e.g., rubbing a sore area)

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6
Q

What is the difference between Aδ and C fibers and Aβ fibers?

A

Aδ and C fibers carry pain while Aβ modulates it

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7
Q

What activates nociceptive neurons, and how is pain signal transmitted?
Activation
Release of mediators
Response pathway
Transmission to CNS

A
  1. Heat, cold, pressure, & tissue injury stimulate nociceptive neurons in the periphery
  2. Injured tissues release substances like bradykinin, prostaglandins, ATP & H+ ions
  3. Mast cells or neutrophils release histamine & Substance P
    CGRP & Substance P cause vasodilation in blood vessels
    Nerve Growth Factor (NGF) and serotonin (5-HT) contribute to pain signal
  4. Signals travel to the dorsal root ganglion (DRG), spinal cord & higher brain centres, creating sensation of pain
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8
Q

How is pain transduced from stimulus to action potential in nociceptive fibres?
Overview
Aβ-fiber
Aδ-fiber
C-fiber

A
  1. Stimulus activates mechanoreceptors or channels, creating a generator potential, which leads to an action potential
  2. Mechanoreceptors trigger Na+ influx via voltage-sensitive sodium channel
  3. Responds to histamine & bradykinin (BK) through H1 & K+ channels
  4. Responds to noxious stimuli through VR1 receptors, allowing Ca2+ & Na+ influx
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9
Q

What stimuli trigger each of the peripheral nerve fibers?

A

Aβ - non-noxious mechanical stimuli
Aδ - noxious mechanical stimuli
C - noxious heat and chemical stimuli

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10
Q

What are the main transducers in nociceptors, and how do they relate to pain perception?
Heat (Capsaicin)
Cold (Menthol)
Acidic environments
Mechanical sensitivity (pressure)
Pathway
Result

A
  1. Activates TRPV1 receptors
  2. Activates TRPM8 receptors
  3. Stimulate ASIC & DRASIC receptors
  4. Activates MDEG, DRASIC, TREK-1
  5. Activation of NaV1.7, 1.8, 1.9 channels generates an action potential
  6. Signal travels through the dorsal root ganglion to the spinal cord & brain, leading to pain sensation & withdrawal or emotional reactions
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11
Q

First and second pain: hand on hotplate example

A
  1. Immediate, sharp, localised pain, transmits by A-delta fibers (myelinated), alerts you to move hand preventing further harm
  2. Slower, duller pain, transmits by C fibers (unmyelinated), sensation lingers with prolonged discomfort, reminder of injury to not re-injure whilst healing
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12
Q

What happens when nociception arrives in spinal cord?

A

Dorsal horn of spinal cord receives nociceptive signals
Integration & transmits information to CNS regions

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13
Q

Pain modulation mechanism theory of pain: Cartesian model of pain

A

This does not explain the whole story: things are more complex that this picture shows
Complexity cannot be explained by a simplistic relationship between peripheral and CNS

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14
Q

Pain modulation mechanism theory of pain: gate theory of pain

A

(Attempted to explain some complexity)
C-fibre nociceptor signal are inhibited at spinal cord level by large nerve fibres (A-alpha, A-beta) before they are transmitted to brain & perceived as pain

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15
Q

Gate theory of pain in practise:
TENS (Transcutaneous Electrical Nerve Stimulator)
Physical therapies (principal of counter-stimulation)
Spinal cord stimulators

A
  1. Used for labour or low back pain
  2. Heat, cold massage, manipulation & acupuncture
  3. Patients with chronic pain when other methods fail, same principle as TENS
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16
Q

Descending modulatory system

A

Descending nerve pathways from brainstem, inhibits facilitate nociceptive signals in spine
Implies pain perceived in brain can be decreased or increased
Hence modification of gate theory to include descending nerves

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17
Q

What neurotransmitters are involved in descending modulation?

A

Opioids
Serotonin (5HT)
Noradrenaline
Gamma amino butyric acid (GABA)

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18
Q

Bidirectional pain network

A

Noxious signal being modulated at several levels between spinal cord and brain
1. Cognition
2. Mood
3. Experience
4. Attention

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19
Q

Types of nociceptive pain

A

Somatic - well-localised, pain receptors in soft tissue, skin, skeletal muscle & bone
Visceral - vague, visceral organs
Neuropathic - damaged sensory nerves

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20
Q

What is nociceptive pain?

A

Response to pathophysiological process occurring in tissues (inflammation)
Pain signal originates in primary afferent nerves signalling noxious events

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21
Q

What are nociceptors?

A

Pain activated by agents like prostaglandins, bradykinin, serotonin, adenosine & cytokines

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22
Q

What is neuropathic pain?

A

Signals generated ectopically without ongoing noxious activity from pathologic route in peripheral or CNS

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23
Q

Pain classification

A

Duration, intensity, presumed pathophysiology (visceral, somatic, sympathetic), opioid sensitivity, pragmatic

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24
Q

Practical pain classification

A

Neuropathic - disordered sensation - anticonvulsants & antidepressants
Bone - intense & focal - NSAIDS & bisphosphonates
Muscle spasm - muscle relaxants & antispasmodics
Cerebral irritation - caused by brain injury, sign of anxiety - BZDs

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25
Q

Pain control mechanisms

A

Aspirin and NSAIDS
Morphine and opioids/cannabinoids
TENS
Deep brain stimulation
Placebo
Acupuncture
Hypnosis

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26
Q

Anatomy of pain pathway

A

Primary afferent neuron –> dorsal root ganglion —> second order neurons –> to brainstem and thalamus

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27
Q

WHO pain ladder and analgesics

A

Step 1. non opioid (paracetamol)
Step 2. weak opioid (codeine mild/moderate pain) + non opioid
Step 3. strong opioid (morphine for moderate/severe pain) + non opioid

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28
Q

WHO cancer pain ladder for adults

A
  1. Non opioid +/- adjuvant (paracetamol & NSAIDS)
  2. Opioid for mild to moderate pain +/- non-opioid & +/- adjuvant (codeine, dihydrocodeine & tramadol)
  3. Opioid for moderate to severe pain +/- non-opioid & +/- adjuvant (morphine, diamorphine, buprenorphine, fentanyl & oxycodone)
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29
Q

What is the afferent and efferent neuron?

A

Afferent - sensory
Efferent - motor

30
Q

What can anti-inflammatory medication inhibit in the pain pathway and what does it cause?

A

NSAIDs can inhibit release of mediators like prostaglandins, reducing inflammation & pain

31
Q

What do the ascending and descending pain pathways do?

A

A: transmits pain signals to brain
D: modulate and inhibit signals to manage pain perception

32
Q

What takes place in the ascending pain pathway?

A

Pain signals travel from C and Aδ fibers in spinal cord brain
Signals pass through medulla, pons & midbrain
They reach the thalamic nuclei and forebrain, processing “early pain” (sharp, initial pain) and “late pain” (dull, prolonged pain)
Reticular formation & periaqueductal gray are involved in pain perception

33
Q

What takes place in the descending pain pathway?

A

Pain modulation starts in the frontal cortex, hypothalamus, and periaqueductal gray
These pathways involve locus coeruleus, raphe nuclei, and medulla, releasing inhibitory signals
Signals descend to the spinal cord, reducing pain transmission from skin & other areas

34
Q

Summary of entire pain pathway:
Site of injury
Spinal cord
Brainstem
Cerebrum

A
  1. Pain begins with injury stimulating unmyelinated C-fibers & myelinated Aδ fibers, detect & transmit pain signal
  2. signal travels along afferent nerves to spinal cord, where synapses & ascends via spinothalamic tract
  3. Signal moves through brainstem, including reticular formation & midbrain, where modulated
  4. Signal reaches thalamus & relayed to cerebral cortex for perception, allowing individual to feel & localise pain
35
Q

Definition of pain

A

An unpleasant sensory & emotional experience associated with, or resembling that associated with, actual or potential tissue damage

36
Q

Major features of pain experience

A

Sensory discriminative
Affective (emotional)
Cognitive

37
Q

What is nociception?

A

Nociception is neural process of encoding noxious stimuli, it is triggered when noxious stimuli act on specialised peripheral nerve endings

38
Q

What can occur in nociception?

A

It does not necessarily result in individual perceiving pain
It also possible for an individual to perceive pain when there is no nociception, occurs in some chronic pain states

39
Q

Types of pain

A

Acute, chronic, malignant vs nociceptive, neuropathic

40
Q

What are the 3 basic causes of pain?

A
  1. Acute trauma or injury
  2. Chronic painful conditions for which cures were unknown
  3. Malignant processes (cancer and arthritis)
41
Q

What 2 types of pain are shown in modern research?

A

Nociceptive pain
Neuropathic pain

42
Q

Where is the cell body located in nociceptors

A
  • Dorsal horn of spinal cord
  • Vagus nodose ganglion
  • Trigeminal ganglia
43
Q

What is a nociceptor?

A

Peripheral sensory terminal (part that senses noxious stimulus)
A central termination within spinal cord or brainstem

44
Q

What activates nociceptors?

A
  1. Physical trauma
  2. Chemicals
  3. Excessive heat or cold
  4. Stretching beyond normal range, which can trigger nociception in muscle
  5. Ischaemia (insufficient blood flow) e.g. angina and inflammation also causes pain
45
Q

What is capsaicin?

A

Gives chilli peppers their heat, may help wound healing by reducing inflammation

46
Q

What are A-alpha/A-beta fibres in nociception?
What type of nociception?
What type of structures are they?
What are the terminals associated with? Transmission speed?

A

Mechanical & thermal nociception
Innervate somatic structures
Terminals associated with specialised sensory structures
Proprioceptive (skeletal muscle, tendon organs), mechanosensitive (light touch)
Very fast (30-120 m/s)

47
Q

What are A-delta fibres in nociception?
What type of nociception?
What type of structures are they?
What type of nerve endings?
Transmission speed?

A

Mechanical, thermal & chemical
Innervate somatic & visceral
Specialised or free
Mechanosensitive (stretch & touch skin, viscera)
Thermosensitive
Fast (4-30m/s)

48
Q

What are C fibres in nociception?
What type of nociception?
What type of structures are they?
What type of nerve endings?
Transmission speed?

A

Mechanical, thermal & chemical
Innervate somatic & visceral
Free nerve endings
Mechanosensitive (stretch & touch)
Thermosensitive
Chemically sensitive (itch)
Slower <2.5m/s

49
Q

Natural products and what can they treat?
Capsicum (TRPV1)
Mentha (TRPM8)
Brassica (TRPA1)
Allium (TRPA1)

A
  1. Heat
  2. Cold
  3. Pain
  4. Pain
50
Q

Cross section of peripheral nerve fibres:
Aβ
Aδ
C

A
  1. Large myelinated fibres (response e.g. to light touch, joint movements)
  2. Small myelinated fibres
  3. Unmyelinated fibres: these conduct very slowly & most of them are those that are involved in generating pain message
51
Q

What is the first and second type of pain and what are the signals carried by?

A
  1. Sharp & brief, myelinated Aδ neurons
  2. More delayed & longer lasting, feels more dull, thin & unmyelinated C fibres
52
Q

What are the 2 possible outcomes when nociception arrives in the spinal cord?

A
  1. Can trigger reflex activity like hotplate example - occurs within spinal cord
  2. Convey information to brain regarding location & intensity of stimulus
53
Q

Function & contribution to pain perception:
Somatosensory cortex
Limbic system
Prefrontal cortex

A
  1. Sensory discrimination & localises site, quality and intensity of stimulus
  2. Affective-motivational function & emotional aspects of pain, attention to & memory of pain
  3. Cognitive evaluation of pain & executive control of purposeful behaviour, emotion, memory and decision making
54
Q

What is somatosensation?

A

Sense of touch, or the ability to perceive stimuli related to temperature, pressure, pain, body position, and balance

55
Q

What is proprioception?

A

Sense of body position and movement

56
Q

What is nociception?

A

Process by which the central and peripheral nervous systems (CNS and PNS) process harmful stimuli, such as tissue damage or extreme temperatures

57
Q

What is acute pain?

A

Sudden, sharp pain that’s usually caused by an injury, illness, or other environmental stress

58
Q

What is chronic pain?

A

Pain that lasts longer than the typical recovery period or occurs along with a chronic health condition

59
Q

What is neuropathic pain?

A

Nerve pain that can happen if your nervous system malfunctions or gets damaged

60
Q

What is allodynia?

A

A condition where a stimulus that normally wouldn’t cause pain results in pain

61
Q

What is noxious stimulus?

A

Physical change that can be internal or external and is strong enough to potentially damage tissue or threaten the body’s integrity

62
Q

What is sensitisation?

A

Process that occurs in the nervous system and a type of non-associative learning

63
Q

What is central sensitisation?

A

Condition where the central nervous system (CNS) becomes hypersensitive to pain and other sensory stimuli

64
Q

What is hyperalgesia?

A

An increased sensitivity to pain or an extreme response to pain

65
Q

What is the dorsal root ganglion?

A

Neural structure in the spinal column that plays a key role in processing and developing chronic pain

66
Q

What are projection neurons?

A

Neurons in the central nervous system (CNS) that send axons from their cell bodies to other regions of the CNS

67
Q

What is the spinothalamic tract?

A

Sensory pathway in the nervous system that carries information about pain, temperature, touch, and pressure from the skin to the brain

68
Q

What are the spinobulbar tracts?

A

Pathways that carry information up and down the spinal cord between brain and body

69
Q

What is the somatosensory cortex?

A

The part of the brain that receives and processes sensory information from the body, such as touch, temperature, and pain

70
Q

What is analgesia?

A

Pain relief or absence of pain

Pharmacy (11 decks)

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