Lecture 41: Pain Flashcards
1
Q
Define “Pain”
A
Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. (International Association for the Study of Pain, 1979)
2
Q
What are the components of pain?
A
-
Sensory
- Here where the point actually feels pain (sharp, achy, heavy etc.)
-
Affective
- Mood, emotion: Anxiety, distress
-
Autonomic
- ↑HR, ↑RR, ↑BP, sweating,
-
Motor
- Withdrawal, lying still, Vocalizing (protection of body)
3
Q
What are the different physiological responses to pain? (autonomic)
A
- ↑HR, ↑RR, ↑BP
- ↓gastric motility
- ↓blood flow to viscera, kidney and skin
- ↑blood sugar
- Nausea
- Pallor
- Diaphoresis
- Dilated pupils
4
Q
Define “Pain Threshold”
A
Pain threshold is the point at which a stimulus is perceived as pain.
Factors affecting threshold include stress, anxiety, culture, previous experience, exercise, activity level, mood, behaviour, emotion, personality, etc.
5
Q
Define Pain Tolerance
A
Pain tolerance is the duration or intensity of pain that an individual will tolerate before i_nitiation of overt pain responses_
- ↓tolerance to pain: repeated exposure to pain; fatigue, anger, boredom, apprehension; sleep deprivation
- ↑tolerance to pain: alcohol consumption; medication, hypnosis; warmth, distracting activities; strong beliefs or faith
6
Q
What increases and decreases your pain tolerance
A
↓tolerance to pain: repeated exposure to pain; fatigue, anger, boredom, apprehension; sleep deprivation
↑tolerance to pain: alcohol consumption; medication, hypnosis; warmth, distracting activities; strong beliefs or faith
7
Q
Describe the relationship between Age and Perception of Pain
A
Age And Perception Of Pain
- Newborns are less sensitive to pain (or they simply lack the ability to verbalise the pain experience).
- Children (15-18 years) have lower pain threshold than adults (feel more pain)
- Adults’ pain threshold tends to increase with ageing (probably caused by peripheral neuropathies and changes in the thickness of the skin)
8
Q
Define Analgesia
A
Analgesia (alg = pain, e.g. myalgia = muscle pain) is absence of pain in response to stimulation that would normally be painful
9
Q
Define Anaesthesia
A
Anaesthesia (esthesia = sensation) is absence of all sensory modalities
10
Q
Define Hyperalgesia
A
Hyperalgesia is an increased response to a stimulus that is normally painful
11
Q
Define Allodynia
A
Allodynia (other pain) is pain due to a stimulus that is not normally painful
12
Q
Define Paresthesia
A
Paresthesia is abnormal sensation of burning, numbness, tingling, itching, prickling (usually caused by nerve compression or damage).
13
Q
Define Causalgia
A
Causalgia is a syndrome of sustained burning pain, and allodynia after a traumatic nerve lesion.
14
Q
Define Central Pain
A
Central Pain is pain associated with a lesion of the central nervous system.
15
Q
Define Nociception
A
Nociception is the sensory process of detecting tissue damage.
16
Q
Noiceptors are….
A
Nociceptors are free nerve endings of primary afferent Aδ (myelinated) and C (unmyelinated) fibers.
- Distributed throughout the body (skin, viscera, muscles, joints, meninges)
- Stimulated by noxious mechanical, thermal or chemical stimuli.
17
Q
Define Noxious Stimuli
A
Noxious Stimulus is a noxious stimulus is one that is due to an event potentially or actually damaging to body tissue.
18
Q
What are the Four Basic Processes Involved In Nociception
A
Four Basic Processes Involved In Nociception (The Sensory Process Of Detecting Tissue Damage)
Four basic processes involved in nociception are
- transduction,
- transmission,
- perception,
- modulation.
- When you have tissue injury, there are mediators that are released
- These stimulate the pain receptors in the skin.
- This external painful stimulus will be converted to an Electrical signal. This process is called Transduction.
- This is followed by transmission of pain (from the skin to the brain where it can be perceived)
- Then we will try to modulate the pain. Inhibitory impulses may come from higher centres to the spinal cord to minimize the pain sensations.
19
Q
What are three categories of noxious stimuli?
A
Three categories of noxious stimuli:
- mechanical (pressure, swelling, tumour growth)
- thermal (burn, scald)
- chemical (excitatory neurotransmitter, toxic substances, ischaemia, infection)
20
Q
Describe the 2 types of pain fibres
1) Characteristics
2) Receptor Type
3) Pain quality
A
C fibres (most numerous 4:1)
Characteristics
- Primary afferent fibres
- Small diameter
- Unmyelinated
- Slow conducting (0.5-2m/sec)
Receptor Type
- Polymodal
- Respond to more than 1 type of noxious stimuli
- Mechanical
- Thermal
- Chemical
- Respond to more than 1 type of noxious stimuli
Pain Quality
- Diffuse, dull
- Burning, aching
- Referred to as ‘slow’ or second’ pain (continuous pain following initial injury)
A-delta fibres
Characteristics
- Primary afferent fibres
- Medium diameter
- Myelinated
- Fast conducting (4-30m/s)
Receptor Type
- Respond to noxious mechano-thermal stimuli over a certain intensity
Pain Quality
- Well-localised, sharp
- Stinging, pricking
- Referred to as ‘fast’ or ‘first’ pain (initial injury)
21
Q
What is transduction?
A
Sensory cells convert external painful stimuli to Electrical signals (action potential)
22
Q
Describe the Transmission process
A
Nociceptor excitation is conducted to the sensory cortex via a combination of:
- Electrical (action potentials)
- Chemical (neurotransmitters (at synapses)
Opioids (narcotics) are effective analgesics because they block release of neurotransmitters
23
Q
Describe the 2nd Order neurons in the Dorsal Horn
A
2nd Order Neurons In DH
Two main classes of dorsal horn cells:
- Nociceptive specific (NS) in lamina I&II activated only by noxious stimuli (A delta and C fibres)
- Wide dynamic range (WDR) in lamina V (or ‘convergent’ neurones) activated by both noxious and innocuous (cutaneous and/or visceral) stimuli (A delta, A beta and C fibres)
24
Q
Describe the pathway of pain from the body
A
Pain From Body
Primary afferents -> DH -> Brain stem -> Thalamus -> Sensory cortex
2nd order neurons from dorsal horn decussates to the other side of the cord and ascends through spinothalamic tract to the thalamus, then to the brain.
25
Describe the pathway of pain from head & face
Pain From Head & Face
* TG sensory nerves
* Trigeminal ganglion (first order)
* Trigeminal spinal nucleus (second order) in brain stem (lower pons & medulla), decussates to join trigeminal lemniscus
* Thalamus
* Sensory cortex.
26
Describe the 2 Divisions of Spinothalamic tract for pain
***Two Divisions Of Spinothalamic Tract (For Pain)***
*_1) N_**_eo-Spinothalamic Tract (Pain Localization Aspect)_*
Aδ fibres, fast pain, starts from _lamina I_ (Posteromarginal nucleus/lamina marginalis), it decussates through anterior commissure and carries information to _midbrain, thalamus and post central gyrus_ (where pain is perceived). It runs laterally.
*_2) Paleo-Spinothalamic Tract (Emotional Aspect Of Pain)_*
C fibres, slow pain, relay with interneurons in _lamina II & III_ (SGR), it then decussates through anterior commissure and carries information to _reticular formation (arousal)_ in _pons & midbrain & limbic system (emotion)._ It runs medially.
27
Describe how pain is perceived multi-dimentionally
Multi-dimentional (perceived in various areas of the brain)
1. **Reticular system** is _autonomic and motor response_ to pain (automatically withdrawing a hand when touching a hot surface)
2. **Limbic system** (lies on both sides of the thalamus) is _emotional and behavioural_ responses
3. **Somatosensory cortex** (postcentral gyrus) is _perception and interpretation_ of sensations
28
Describe the moduation of pain
It is well known that there are individual differences between _objective reality and subjective response_ to a painful stimulus.
This implies that there is a _mechanism in the body that modulates pain perception._
The transmitted pain signal is liable to _**dampening** (down-regulation)_ and _**amplification** (up-regulation_).
Most of _modulations occur in dorsal horn!_
29
Describe the ***Segmental Inhibition***
_**Gate control theory** (modulation of pain)_ is based on the premise that a gate, located in _dorsal horn_ of spinal cord, modulates _afferent nerve impulses_.
This implies that a _non-painful stimulus_ can block transmission of a noxious stimulus.
**_Three input variables affect this gate:_**
1. A **delta** and **C** fibres (blue) _opens_ the _gate_
2. **A-beta** fibres carry messages of light touch **_close_**s the gate
3. Messages from the brain _open or close_ the gate
**_Mechanism:_**
* There are _special inhibitory inter-neurons in the spinal cord_, i.e. they keep the gate closed.
* These _special neurons_ make a pain blocking endogenous opioid called **_enkephalin_**. This is opiate-like _which blocks neurotransmitters release_ from _C and A-delta fibres_ and this keeps gate closed.
30
What are the 2 systems of the the Pain Dampening theory?
Pain dampening include
(1) **segmental inhibition** (gate control theory);
(2) **descending inhibitory** nerve system.
31
Describe the ***Descending Inhibitory Nerve System (Descending Modulatory Pain Pathway DMPP)***
***Descending Inhibitory Nerve System (Descending Modulatory Pain Pathway DMPP)***
Descending axons transmit impulses from the brain stem to the spinal cord (lamina) to reduce pain:
① Stimulation of _periaqueductal gray area_ (PAG) in midbrain by ascending pathways of pain signal, activates neurons that project to
* _locus ceruleus (LC) in pons,_
* _nucleus raphe magnus (NRM) in medulla_
② Descending neurons (yellow) from _LC and NRM_ release _noradrenaline_ and _5-HT_ respectively, _stimulate inhibitory interneuron_s in DH that release **_enkephalin_**.
32
What are some conditions that open and close the gate?
1) Physical condition
2) Emotional conditions
3) Metnal conditions
(see pic)
33
Give some examples of Gate Control theory
* _Bumping the head (_the initial trauma activates A-delta and eventually, C fibers; **rubbing** traumatized area stimulates A-beta fibers, which activate DH to close the spinal gate, thus inhibiting transmission of the painful stimulus)
* Transcutaneous electrical nerve stimulation (TENS)
* Acupuncture
34
Describe **Pain Amplification (Up-Regulation):** **Windup** **(Hypersensitivity Or Hyperexcitability)**
**Pain Amplification (Up-Regulation):** **Windup** **(Hypersensitivity Or Hyperexcitability)**
***Definition***
Windup is the process of _increased action potential output from dorsal horn cells_ in response to _sustained low frequency input_ from nociceptive afferents via _C fibres to DH neurones_ (i.e. central sensitization of pain)
***Mechanism of Windup***
Receptors (AMPA, NMDA & NK1) on DH neurons are stimulated by _↑glutamate and ↑substance P_ production from _C fibres_ terminals due to their continuous stimulation for an _extended period_ from peripheral receptors.
This leads to _increased calcium influx_ in the DH neurons. Consequently:
* Excessive activation of NMDA receptors and more calcium influx lead to pathophysiologic changes in DH neurons by _lowering of receptors’ threshold_, thus becoming _more responsive_ to all its inputs.
* This results in central sensitization (sensation of pain is heightened), thus _2o Hyperalgesia, allodynia_
*NMDA receptor inhibitors ketamine and methadone prevent 'windup' and may play a central role in managing chronic pain.*
35
Define Pain amplification
_Windup_ is the process of i_ncreased action potential output_ from dorsal horn cells in response to _sustained low frequency input from nociceptive afferents_ via C fibres to DH neurones (i.e. central sensitization of pain)
36
Describe the Mechanism of Windup
***Mechanism of Windup***
Receptors (AMPA, NMDA & NK1) on Dorsal Horn neurons are stimulated by _**↑glutamate** and **↑substance P**_ production from _C fibres_ terminals due to their continuous stimulation for an _extended period_ from peripheral receptors.
This leads to _increased calcium influx_ in the DH neurons.
Consequently:
* _Excessive activation of NMDA_ receptors and m_ore calcium influx_ lead to pathophysiologic changes in DH neurons by _lowering of receptors’ threshold_, thus becoming _more responsive_ to all its inputs.
* This results in central sensitization (sensation of pain is heightened), thus _2o Hyperalgesia, allodynia_
*NMDA receptor inhibitors ketamine and methadone prevent 'windup' and may play a central role in managing chronic pain.*
37
Define Nociceptive pain
**Nociceptive Pain**
Nociceptive pain is due to stimuli from _somatic and visceral_ structures after _tissue damage_:
1. chemical (decreased PH),
2. intense heat (above 42C),
3. mechanical forces.
This is usually _opioid sensitive_.
38
What are the different types of pain?
1) Nociceptive Pain
* Pain due to destruction of tissues
2) Neuropathic Pain
* Pain due to damage to the nerves
3) Inflammatory Pain
* Pain due to inflammation (inflammatory cells release mediators that cause pain)
4) Referred Pain
39
What is neuropathic Pain and what is it sensitive to?
Neuropathic pain is due to _damaged neuronal_ structure. This is usually _opioid resistant_, but sensitive to:
* _Membrane stabilizers_ (gabapentin, carbamazepine)
* _Tricyclics_ (amitriptyline) (antidepressants)
* _Spinal cord stimulato_r (electrical pulses) (gate control theory)
Neuropathic pain frequently coexists with nociceptive pain.
40
Describe the Nociceptive Pain Pathway
* Tissue damage happen. the mediators are released (e.g. K+, PG, serotonin)
* These stimulate the noiceptors (Transduction occurs)
* The electrical signal goes to the 2nd order neurons and then into the brain
* The release of neurotransmission from the first order neurons to the second order neurons occurs.
41
What are algestic substances?
Substances that can cause pain
e.g. K+, serotonin, bradykinin, histamine, PGs, leurkotriene, substance P
42
What are the types of neuropathic pain?
***Types Of Neuropathic Pain***
***_1) Peripheral (Outside CNS)_***
* Burning, tingling, shooting, stinging, or "pins and needles" sensation.
* This include _diabetic neuropathy, trigeminal neuralgia, postherpetic zoster pain_.
***_2. Central_***
* This include _thalamic pain syndrome_ (Dejerine-Roussy disease) (after a stroke when it affects the thalamic sensory relay nuclei), and
* _damage to spinal cord_ (e.g. compression of tumour).
***_3. Complex Regional Pain Syndrome (CRPS)*_ _*(_****Different names: Reflex Sympathetic Dystrophy (RSD), Causalgia, Sympathetically Maintained Pain)*
* This is _caused_ by major injury or relatively minor trauma.
* _Symptoms_ include severe debilitating pain.
* _Signs_ in affected limb are:
* Abnormal circulation, temperature, sweating (related to sympathetic nervous system, hence also named reflex sympathetic dystrophy)
* Loss of function
* Atrophy of muscles
* Changes in the hair and skin
Management include _physical therapy,_ _sympathetic nervous system blocks_, _medication_.
43
Can neuropathic pain coexist with nociceptive pain?
Yes.
44
Describe the 2 entities of Inflammation
Inflammation may be divided into two entities: (1) **_non-neurogenic inflammation_**; (2) **_neurogenic inflammatio_**n
* **_Non-neurogenic inflammation_** involves _release of inflammatory substances_ (e.g. histamines, prostaglandins, cytokines, leukotrienes, bradykinin, etc) from the _blood vessels and connective tissue_.
* **_Neurogenic inflammation_** includes _release of neuropeptides_ (e.g. substance P, calcitonin gene related peptide [CGRP], noradrenaline, etc.) from _C-fibers terminals._
* __SP, CGRP, NKA will act on Mast cells and Blood vessels to release Histamine, 5HT, GP, Bradykinin
* These will act on the blood vessels to cause _vasodilation_ and _oedema_ (wheal and flare response)
* NKA (neuropeptides) will also act on the inflammatory cells in this area to produce even more inflammatory mediators to affect the receptors to make them more responsive to pain _Peripheral sensitization_)
* If this happens for a long time without treatment, this results in (in 2nd order dorsal neuron) you get _Central Sensitization (windups)_
* Spontaneous pain, pain hypersensitivity, allodynia and _II Hyperalgesia_
Both processes lead to _lowering receptors’ threshold thus hyperalgesia_.
45
What is Inflammatory Pain?
What are the 2 types of hypersensitivity to noiceptors?
It is a post-traumatic pain which includes: (1) tissue damage (trauma, heat, chemicals, radiation, infection, immunological reaction); (2) inflammatory mediators (peripheral sensitisation)
A feature of inflammatory pain is the development of _hypersensitivity_ to nociceptors (decreased threshold) so that stimuli, which normally would not produce pain, begin to do so.
This is the result of the production of a broad range of _inflammatory mediators_ that act on the high-threshold primary-sensory neurons and change their properties.
There are 2 major features underlying inflammatory pain:
1. Peripheral sensitization of high-threshold nociceptors, leading to _primary hyperalgesia_ (e.g. sunburn inflammation)
2. Increase in excitability or responsiveness of neurons within CNS, thus increasing gain of system (windup), hence central sensitization, leading to _secondary hyperalgesia / allodynia_.
* Primary hyperalgesia is when injurious area decrease pain threshold.*
* Secondary hyperalgesia is when non-injurious area decrease pain* threshold.
46
What are the 2 types of hyperalgesia?
**_1) Primary hyperalgesia_**
* *Primary hyperalgesia is when injurious area decrease pain threshold.*
**_2) Secondary hyperalgesia_**
* *Secondary hyperalgesia is when non-injurious area decrease pain* threshold.
* This is because the touch in this area will be now sensed as pain by the 2nd order neurons (because the threshold has reduced)
47
A feature of inflammatory pain is \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
A feature of inflammatory pain is the development of _hypersensitivity to nociceptors_ (decreased threshold) so that stimuli, which normally would not produce pain, begin to do so.
48
What is referred pain?
Referred pain is when _body interpret visceral pain_ of internal structures on a _cutaneous level of body surface_ (dermatome) due to sharing of some _2nd order neuron._
e.g. apendicitis
49
What is the difference between Acute and Chronic Pain?
**_Acute Pain_**
* Has biologic function
* Acts as warning system indicating tissue injury
* Recent onset
* Finite duration (days to weeks)
* Remits when underlying pathology resolves
**_Chronic Pain_**
* No biologic value
* Detrimental effects
* Persists beyond usual course of acute illness or injury (longer than 3 months)
* Chronic pathologic process; can recur at intervals
50
Describe the Transition from acute to chronic pain
1) Injury associated inflammation occurs
2) Transient activation of noiceptive fibres
3) Sustained stimulation results in Sesnsitization of the noiceptive fibres (hyperalgsia I and II)
4) If this occurs for a longer time, there is CNS neuroplastiticity (structural modelling) = **Chronic Pain (V. difficult to treat)**
51
Describe the Chronic Pain Mechanism of Chronic Pain
* The source of pain (red) is continuously producing impulses and these impulses will sensitize the 2nd order neuron (result in primary and secondary hyeralgesia)
* The neurotransmitter release at the C-fibres are going to affect _Glial Cells_.
* The Glial cells will produce _cytokines_ which will stimulate the C-fibres to release even more transmitters (viscious circle)
* So the Pain is now generated in the dorsal horn (not at the periphery)
* So even if the source of the pain is treated, the _patient still feels pain_.
This is the basis from Chronic Pain. (Ignoring of the pains source)
52
What is central sensitization (windup)
Spontaneous Pain
Pain hypersensitivity
Allodynia
II hyperalgesia
Chronic pain
53
How do you assess pain?
1) Verbal scale
2) Visual Analogue scale
3) Numerical Rating Scale
4) Wong-Baker FACES scale
This uses McGill pain questionnaire (multi-dimensional), including sensory and affective.
**Pain Intensity Categorisation**
It is common to use a numeric scale to rate pain intensity where 0 = no pain and 10 is the worst pain imaginable:
* Mild: \<4/10
* Moderate: 5/10 to 6/10
* Severe: \>7/10
