Lecture 44: Pain physiology Flashcards
What is the difference between pain and nociception
Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage.
Nociception is the sensory process of detecting tissue damage in somatic and visceral structures : (drop in pH, heat >42, mechanical forces)
1.Transduction, 2.Transmission, 3.Perception, 4.Modulation,
What are the 4 components of pain
- Sensory: sharp, achy, heavy
- Affective: Mood, emotion
- Autonomic : mainly sympathetic
- Motor: withdrawal from the pain source, immobilisation, vocalisation
What are the physiological responses to pain
Mainly sympathetic effects: Increased HR, BP, RR and Blood sugar.
Decreased gastric motility, blood flow to viscera.
Pallor, dilated pupils. diaphoresis (excessive sweating), nausea
What is the pain threshold
The point at which a stimulus is perceived as pain
What is pain tolerance and the factors that affect it
- Duration or intensity of pain that an individual will tolerate before initiation of overt pain response.
- Decreased tolerance: repeated exposure to pain, fatigue, boredom, apprehension, sleep deprivation
-Increased tolerance:
alcohol consumption, medication, hypnosis, warmth, distracting, strong beliefs/faith
How does pain threshold change with age and why
Newborns: less sensitive to pain- or can’t say so
Children (5-18): lower pain threshold than adults
Adults: pain threshold increases with aging as skin becomes more thick so will not be sensitive to pain + peripheral neuropathies
Define hyperalgesia, allodynia, causalgia
Hyperalgesia: An increased response to stimulus that is normally painful (heightening pain) whereas
Allodynia: pain due to stimulus that is not normally painful.
Causalgia: a syndrome of sustained burning pain + allodynia after a traumatic nerve lesion
Define anaesthesia vs analgesia, Paraesthesia vs central pain
Anaesthesia: absence of all sensory modalities whereas Analgesia: absence of pain in response to stimulation that would usually be painful.
Paresthesia: Abnormal sensation of burning, itching, numbness, tingling usually caused by nerve compression or damage
Central pain is pain associated with lesion of the CNS
What is a noxious stimulus
Stimulus that can is potentially or actually damaging to tissue (drop in pH, heat >42, mechanical forces)
Compare the two fibres that transmit pain and their two nociceptor types- what characteristic of pain, speed
Receptors:
A delta: First pain: fast- sharp, localised, sting:
- Respond to noxious Mechano-thermal stimuli over a certain intensity
C fibres: 2nd pain: slow- dull, diffuse ache:
-Respond to more than one type of noxious stimuli: Mechanical, Thermal, Chemical
Fibres:
A delta: fast- myelinated, medium diameter,
C fibres: slow-unmyelinated, small diameter
Describe what happens at the Transduction step and where
At Level of tissues
- Noxious stimuli cause release of chemicals- SubP, PG, 5HT, ACh
- Activating nociceptors
- Leading to AP
Describe what happens at the Transmission step and where
Nociceptor excitation is conducted via a combo of Electrical AP and chemical neurotransmitters at the synapses.
- 1st order neuron enters SC through Dorsal root where it synapses with 2nd order neuron in Dorsal horn
- 2nd order neuron decussates through ventral white commisure, travels up through brainstem and then synapses with thalamus
- 3rd order neuron goes to then to sensory cortex
What are the two main classes of dorsal horn cells that the 1st order neuron synapses with, which lamina, stimuli and the fibres that innervate them
- Nociceptive specific cells: in rexed lamina 1 and 2 activated only by noxious- high intensity stimulation
(a- delta or c fibres) - Wide dynamic range: rexed lamina 5. Activated by both noxious and innocuous cutaneous or visceral stimuli (eg. touch)
(A delta, C and A beta fibres)
What are 3 examples of excitatory neurotransmitters and 3 inhibitory
Excitatory:
- ACh,
- monoamines (NE, dopamine, Histamine),
- neuropeptides (sub P)
Inhibitory:
- GABA in brain
- Glycine in spinal cord
- Endogenous opioids (enkephalin, endorphin, dysnorphin)
What is the pathway of pain transmission from the head and face to sensory cortex
- 1st order neuron: TG sensory nerves-> trigeminal ganglion
- 2nd order Go to Trigeminal spinal nuc. in the Brainstem ( lower pons+ medulla)
- Decussates to join the Trigeminal lemniscus. goes to the Thalamus
- 3rd order: Thalamus-> cortex
What is the Neo-spinothalamic tract and Paleospinothalamic divisions of the spinothalamic tract for pain
- Neo: for A-delta (lateral). Starts from lam 1 then decussates through ant commissure carrying info through midbrain, thalamus to Post Central Gyrus.
- Paleo: C fibres (medial)
relay with interneurons in lam 2&3 then decussates through ant commissure carrying info to Reticular formation in pons/midbrain and to the Limbic system for emotion
Where is Perception of pain processed and what response/sensation does it control
Done in
1. Reticular system: autonomic and motor response to pain
- Limbic system: emotional and behavioural response
- Somatosensory cortex: perception and interpretation of sensation (localisation)
What is Modulation of pain and what are the ways it occurs
Modulation of pain: where there is a difference between the objective reality and subjective response to a painful stimulus
Pain signal
- Dampening: Gate control
a) segmental inhibition:
b) descending inhibitory nerve from higher systems - Amplification
a) Windup in dorsal horn
Explain Gate control theory and how it helps to dampen pain signals-
a non painful stimulus can block the transmission of noxious stimulation
At the segmental level
- A-delta and C fibres synapse with 2nd order neuron to the cortex at the segmental level
- However inhibitory interneurons synapse on the 2nd order neuron as well.
- They produce enkephalin (opioid) which bocks neurotransmitter release from A-delta + C fibres, therefore stopping pain transmission to the brain.
- The inhibitory interneuron is stimulated by A beta fibres (carrying light touch information)
What path does descending inhibitory nerve take to stimulate the inhibitory interneuron in the spinal segment
- in the Midbrain, periaqueductal grey is stimulated by ascending pain signal
- This activates neurons to
a) Locus ceru leus in Pons
b) Nucleus Raphe magnus in medulla - Descending neurons from LC and NRM go to inhibitory interneuron in spinal segment and release Noradrenaline and 5HT respectively
- Leads to enkephalin production
What are the physical, emotional and mental conditions that will open gate to pain or close it
Physical
- O: Injury is super bad.
- C: Medications like opioids can block the gate.
Emotional:
- O: Anxiety, worry tension
- C: Positive emotions, relaxation
Mental :
- O: focusing on pain + boredom-
- C: Intense concentration or distraction. life activities
What does Wind up (Pain amplification) mean and what two conditions does it cause
Process of increased AP output from the 2nd order dorsal horn cells in response to sustained low frequency input from nociceptive afferents via C fibres.
(when pain isn’t treated properly)
leading to formation of
2ndary hyperalgesia and allodynia
What is the mechanism of Windup
- Extended source of pain stimulates C fibres, leading to increased glutamate and Substance P release.
- This stimulates
receptors on the 2nd order neuron in the dorsal horn (AMPA, NMDA, NK1) which leads to increased calcium influx in the 2nd order neurons - This causes pathophysiological changes in 2nd order neurons = lowering of receptors threshold
- Thus becoming more responsive to all its inputs - even touch stimulus
- This would cause central sensitization - heightened sensation of pain and 2ndary hyperalgesia and allodynia
What algesic substances are released from damaged cells, platelets, plasma, mast cells, and 1’ nerve afferents that triggers nociceptors
Damaged cells: leukotriene, PGs, K
Platelet: 5HT
Plasma: bradykinin
Mast cells: histamine
1’nerve afferents: Substance P
What are the 3 types of Neuropathic pain and what is it sensitive to (not opioids)
- Peripheral neuropathic pain- nerves damaged themselves eg. trigeminal neuralgia: a-delta type pain or pins and needles
- Central:
Thalamic pain syndrome after stroke in thalamic sensory relay or damage of the spinal cord - Complex regional pain syndrome/aka reflex sympathetic dystrophy/causalgia
Treatments: membrane stabilisers, tricyclics, spinal cord stimulator.
What are the causes, symptoms and treatment of Complex regional pain syndrome
Due to major injury/trauma there is severe debilitating pain.
In the affected limb there is abnormal circulation, temperature, sweating, loss of function, atrophy, change in hair and skin.
Management is through physical therapy, symp NS blocks and other medications
What are the two types of Inflammation (after tissue damage) and which type of hyperalgesia does it cause
(Inflammatory mediators cause changes in pain receptors - lowering their threshold so more sensitive to touch stimulus )
- Non-neurogenic: Initial pain: 1’ hyperalgesia due to release of algesic substances from bv and CT
- Neurogenic: 2nd pain: 2’ hyperalgesia due to the release of neuropeptides (SubP, CGRP, NA) from C fibres which act on Mast cells and BV to release more inflam mediators to cause oedema and vasodilation and enter + feedback loop= windup
What is the mechanism of referred pain
Neurons supplying the internal organ enter the spine at the same level as cutaneous sensory nerves so brain interprets it as coming in from the dermatome of the cutaneous nerve.
Compare acute vs chronic pain: duration, function, onset
Acute has a biological function - warning of tissue injury with a finite duration - recent onset and remits when underlying pathology is resolved.
However Chronic pain has no biological value and persists beyond usual course of acute injury and can recur at intervals
Describe the process of transition from acute to chronic pain starting at inflammation from surgery/injury
- First there is transient activation of nociceptive fibres
- However, after sustained stimulation they get sensitization of nociceptors: 1’ or 2’ hyperalgesia
- If there is untreated extended source of pain, the C terminal molecules stimulate glial cells in the dorsal horn to make Cytokines.
- These will stimulate the afferent c fibres coming in, starting automatic pain signal generation in DH, making a loop,
Even if the source of pain isn’t there-
What are the 5 behavioural and psychological changes in Chronic pain
Depression, anxiety, unease, unpleasantness, fear, sleeping disorders.
How is pain assessed
-Verbal scale,
-Visual analogue scale (line)
-Numerical rating: 1-10.
Mild: less than 4
Moderate: 5-6.
Severe: 7+
-Wong baker faces scale for kids.
