Lecture 41: Pain Flashcards
Define “Pain”
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)
What are the components of pain?
-
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)
What are the different physiological responses to pain? (autonomic)
- ↑HR, ↑RR, ↑BP
- ↓gastric motility
- ↓blood flow to viscera, kidney and skin
- ↑blood sugar
- Nausea
- Pallor
- Diaphoresis
- Dilated pupils
Define “Pain Threshold”
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.
Define Pain Tolerance
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
What increases and decreases your pain tolerance
↓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
Describe the relationship between Age and Perception of Pain
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)
Define Analgesia
Analgesia (alg = pain, e.g. myalgia = muscle pain) is absence of pain in response to stimulation that would normally be painful
Define Anaesthesia
Anaesthesia (esthesia = sensation) is absence of all sensory modalities
Define Hyperalgesia
Hyperalgesia is an increased response to a stimulus that is normally painful
Define Allodynia
Allodynia (other pain) is pain due to a stimulus that is not normally painful
Define Paresthesia
Paresthesia is abnormal sensation of burning, numbness, tingling, itching, prickling (usually caused by nerve compression or damage).
Define Causalgia
Causalgia is a syndrome of sustained burning pain, and allodynia after a traumatic nerve lesion.
Define Central Pain
Central Pain is pain associated with a lesion of the central nervous system.
Define Nociception
Nociception is the sensory process of detecting tissue damage.
Noiceptors are….
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.
Define Noxious Stimuli
Noxious Stimulus is a noxious stimulus is one that is due to an event potentially or actually damaging to body tissue.
What are the Four Basic Processes Involved In Nociception
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.
What are three categories of noxious stimuli?
Three categories of noxious stimuli:
- mechanical (pressure, swelling, tumour growth)
- thermal (burn, scald)
- chemical (excitatory neurotransmitter, toxic substances, ischaemia, infection)
Describe the 2 types of pain fibres
1) Characteristics
2) Receptor Type
3) Pain quality
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)
What is transduction?
Sensory cells convert external painful stimuli to Electrical signals (action potential)
Describe the Transmission process
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
Describe the 2nd Order neurons in the Dorsal Horn
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)
Describe the pathway of pain from the body
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.
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.
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.
Describe how pain is perceived multi-dimentionally
Multi-dimentional (perceived in various areas of the brain)
- Reticular system is autonomic and motor response to pain (automatically withdrawing a hand when touching a hot surface)
- Limbic system (lies on both sides of the thalamus) is emotional and behavioural responses
- Somatosensory cortex (postcentral gyrus) is perception and interpretation of sensations
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!
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:
- A delta and C fibres (blue) opens the gate
- A-beta fibres carry messages of light touch closes the gate
- 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.
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.
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.
What are some conditions that open and close the gate?
1) Physical condition
2) Emotional conditions
3) Metnal conditions
(see pic)
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
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.
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)
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.
Define Nociceptive pain
Nociceptive Pain
Nociceptive pain is due to stimuli from somatic and visceral structures after tissue damage:
- chemical (decreased PH),
- intense heat (above 42C),
- mechanical forces.
This is usually opioid sensitive.
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
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.
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.
What are algestic substances?
Substances that can cause pain
e.g. K+, serotonin, bradykinin, histamine, PGs, leurkotriene, substance P
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.
Can neuropathic pain coexist with nociceptive pain?
Yes.
Describe the 2 entities of Inflammation
Inflammation may be divided into two entities: (1) non-neurogenic inflammation; (2) neurogenic inflammation
- 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
- If this happens for a long time without treatment, this results in (in 2nd order dorsal neuron) you get Central Sensitization (windups)
- __SP, CGRP, NKA will act on Mast cells and Blood vessels to release Histamine, 5HT, GP, Bradykinin
Both processes lead to lowering receptors’ threshold thus hyperalgesia.
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:
- Peripheral sensitization of high-threshold nociceptors, leading to primary hyperalgesia (e.g. sunburn inflammation)
- 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.
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)
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.
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
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
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)
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)
What is central sensitization (windup)
Spontaneous Pain
Pain hypersensitivity
Allodynia
II hyperalgesia
Chronic pain
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
