Pain Flashcards
Pain
An unpleasant sensory and emotional experience associated with or resembling that associated with actual or potential tissue damage
Purpose of immediate pain
Warns of imminent tissue damage —>withdraw from the source of injury
Purpose of persisting pain
Encourages us to immobilise the injured area, giving damaged tissue the best chance to heal
Nociception
Describes the neural processes involved in producing the sensation of pain
Nociceptive pathways
Transduction in the periphery, through transmission to the dorsal horn of the spinal cord, then on to the brain
Acute pain
Pain <12 weeks duration
Chronic pain
Continuous pain lasting >12 weeks
Pain that persists beyond Tissue healing time
2 types of chronic pain
Non-cancer
Cancer
Nociceptive pain
Pain that arises from actual or threatened damage to non-neural tissue and is due to activation of nociceptors
Neuropathic pain
Pain caused by a lesion or diseases of the somatosensory nervous system
Nociplastic pain
Pain that arises from altered nociception despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors, or evidence for disease or lesion of the somatosensory system causing pain
Examples of neuropathic pain
Trigeminal Neuralgia
Glossopharyngeal Neuralgia
Post Herpetic Neuralgia
Painful Diabetic Neuropathy
Complex Regional Pain Syndrome
Phantom limb pain
Pain due to spinal cord damage / stroke / brachial plexus avulsions
Allodynia
Pain due to a stimulus that does not normally provoke pain
Dyesthesia
An unpleasant abnormal sensation, whether spontaneous or evoked
Hyperalgesia
Increased pain from a stimulus that normally provokes pain
Hypoalgesia
Dismissed pain in response to a normally painful stimulus
Pain pathways
Peripheral receptor
1st order neurons
2nd order neuron
3rd order neuron
1st order neuron
From the periphery to ipsilateral spinal cord
2nd order neuron
Crosses to the contralateral cord and ascends to the thalamus, the system’s integrative ‘relay section’
3rd order neuron
From thalamus to midbrain and higher cortical centres
Nociceptors
Transduction
Physical stimulus —> Action potential
Most are poly-modal (thermal/chemical/mechanical)
Primary Afferent neurones
Nociceptors are the free nerve endings of primary afferent neurons
AΔ fibres
C fibres
found in any area of the body that can sense pain either externally or internally
External: skin / cornea / mucosa
Internal: viscera / joints / muscles / connective tissue
The cell bodies of these neurons reside in either
Dorsal root ganglion (body)
Trigeminal ganglion (face / head / neck)
Cell bodies of primary Afferent neurones are found in either
Dorsal root ganglion (body)
Trigeminal ganglion (face/head/neck)
Dorsal root ganglion
Present on the dorsal root (sensory)
Composed of cell bodies of nerve fibres that are sensory (afferent)
First order neurons
Pseudo-unipolar neurons
Can be the source of pain pathology
Trigeminal ganglion is the equivalent for the face / head
A-Alpha nerve fibre carries what kind of information
Proprioception
A-beta nerve fibre carries what kind of information
Touch
A-delta nerve fibre carries what kind of information
Pain (mechanical and thermal)
C nerve fibre carries what kind of information
Pain (mechanical, thermal and chemical)
Which nerve fibres are myelinated
A-Alpha
A-beta
A-delta
Which nerve fibre is unmyelinated
C
A-Alpha nerve fibre diameter
13-20 um
A-beta nerve fibre diameter
6-12 um
A-delta nerve fibre diameter
1-5 um
C nerve fibre diameter
0.2-1.5 um
A-Alpha nerve conduction speed m/s
80-120
A-beta nerve conduction speed m/s
35-90
A-delta nerve conduction speed m/s
5-40
C nerve conduction speed m/s
0.5-2
Dorsal horn
On the posterior aspect of the SC the grey matter forms two horns called the dorsal horns. (the ones at the front are called the ventral horns)
Contains distal nerve endings from primary afferents, cell bodies of second order neurones as well as a complex network of other nerves such as excitatory and inhibitory interneurons (and projection neurones) that transmit somatosensory info from the SC to the brain
2 dimensions of pain experience
- Sensory/discriminative- allowing us to locate tissue damage
- Affective/aversive- ‘unpleasant’ and ‘emotional’ in the IASP definition
his is reflected in the anatomy of the different components of the pain pathway:
The affective component travels centrally along ancient spinal cord pathways to ‘old brain’ centres in the midbrain
The discriminative part of the sensation is carried along newer tracts to the evolutionary modern sensory cortex
Polymodal nociceptors
A-delta and C - respond to a variety of stimuli, mechanical, thermal and chemical.
A-delta nociceptors
thought to mediate the initial, ‘fast’ pain on injury, e.g. on touching a red-hot surface. This ‘fast pain’ initiates the protective withdrawal reflex.
C nociceptors
responsible for the dull, throbbing pain that accompanies inflammation following injury. This ‘slow pain’ promotes immobilization of the injured body part, which can encourage healing
Visceral nociceptors
similar to Aδ and C nociceptors found in the periphery. The main difference being that they respond to distension and ischaemia rather than cutting and thermal damage. Visceral pain signals are carried by Aδ and C fibres, which travel with autonomic efferents
Activation thresholds
Activation thresholds for mechanical and thermal stimulation are high compared to mechanoreceptors and thermoreceptors. In other words, it is extremes of pressure and temperature that activate nociceptors.
How do A-delta afferents synapse
Aδ primary afferents synapse directly withsecondary afferentsthat will eventually carry the pain signal to the thalamus.
How do C fibre afferents synapse
C fibres do not synapse directly with secondary afferents, but connect instead withinterneuronsthat carry the signal on to secondary afferents in laminae I or V. These interneurons are important in modulation of the pain signal
Visceral input
differs in that fewer primary afferents activate a larger number of second order neurons, resulting in poorer localisation of pain. Visceral afferents also converge with somatic inputs, which may account for the phenomenon of referred pain
Spinothalamic tract
Sensory pathway that carries pain, temperature and crude touch information from the body
2nd order neurons
Originate in the spinal cord (substantia gelatinosa and nucleus proprius)
Axons decussate at / few levels above the site of entry / spinal segment
Cross the midline in the anterior commissure
Then form the anterolateral tract
lateral STT (pain & temperature) and
anterior STT (crude touch)
Terminate in the thalamus
(ventral posterior lateral nucleus)
Some axons terminate in the reticular
formation and midbrain
Where does the Spinothalamic tract originate
Spinal cord- Substantia gelatinosa and nucleus proprius
Where do fibres of the Spinothalamic tract terminate
Thalamus (ventral posterior lateral nucleus)
Lateral Spinothalamic tract
Pain and temperature
Anterior Spinothalamic tract
Crude touch
Where do axons of the Spinothalamic tract decussate
at / few levels above the site of entry / spinal segment
Ventral Spinothalamic tract
Light touch
Dorsal columns
Fine touch
Proprioception
Vibration
Medial Spinothalamic tract
ascends deeper in the cord, sending collaterals to the reticular activating system, periaqueductal grey and hypothalamus, before terminating in the medial nucleus. It serves the general arousal and aversive component of the pain experience.
Lateral Spinothalamic tract
originates from secondary afferents in laminae I and V of the dorsal horn, and runs superficially in the anterolateral white matter cord, ascending directly to the lateral thalamus. As the name suggests, it is the newer of the two spinothalamic tracts and carries the sensory, discriminative part of the pain signal
Thalamus
Midline, paired symmetrical structure in the brain
Approx 6 X 3 cms long
All sensations (except olfactory) relay / pass through
Multiple nuclei
VPL
Medial group
Reciprocal connections to all parts of the cortex
Thalamic nuclei
The main thalamic nuclei involved in pain processing are:
Lateral ventral posterolateral (VPL) nuclei
Medial midline group of nuclei
The thalamic nuclei contain cell bodies of third order neurons, the projections of which make up the final part of the nociceptive pathway.
Lateral Thalamic nuclei
Sensory component
Medial Thalamic nuclei
Emotional component
Sensory cortex
Broadmann area 3, 1, 2
Every area on the body is represented in a spatial fashion Sensory homonculus
Insula
where the degree of pain (experienced or imagined) is judged
Contributes to the subjective aspect of pain perception
Plays a role in perception, motor control, self awareness and interpersonal experience
May also play a part in addiction
Amygdala
plays a key role in learned emotional responses (fear, anxiety, depression)
important brain center for the emotional-affective dimension of pain and for pain modulation
hyperactivity in the central nucleus of the amygdala accounts for pain-related emotional responses and anxiety-like behavior
Cingulate cortex
Located on the medial aspect of the cerebral hemispheres
Intricately linked with the limbic system which is associated with emotion formation and processing, learning and memory
Maintains reciprocal connections with other pain processing areas
Has recently been shown to be one of the areas activated by acupuncture
Where is the peri-aqueductal gray
In brainstem
Peri-aqueductal gray
Grey matter located around the cerebral aqueduct
Receives input from cortical and sub-cortical areas
Projects onto neurons in the dorsal horn
Modulate afferent noxious transmission
Neurons bear opioid receptors
Pathways also include noradrenergic and serotonergic neurones
Stimulus of the PAG can result in profound analgesia
Pain treatment
Stimulate descending inhibitory pathway
Gate control
Pharmacotherapy
Gate control theory
concept that onwards transmission of a nociceptive signal depends on the balance between inhibitory and excitatory inputs at points of integration along the path from transduction to perception.
Pain management
MDT approach
Biological target
Physio therapy / occupational therapy
Psychology
Drugs commonly used in pain medicine
NSAID’S
Paracetamol
Opioids
LA’s
⍺2 agonists
NMDA receptor antagonists
TCA’s
gabapentinoids
SNRI’s
Opioids use
Treat acute pain
Problems with long term use of opioids
Tolerance (challenge in acute pain settings)
Immunosuppression
Deranged HPAxis
Opioid Induced Hyperalgesia (OIH)
Causes of cancer pain
- Pain associated with direct tumor (tumor infiltration, bone metastases)
- Pain associated with cancer therapy (chemo, surgery or radiation)
- Pain unrelated to cancer (RA, OA, headache or herpes zoster)
Anterior cingulate cortex
number of functions, including attention and response selection.
Activation studies suggest the ACC plays an important role in processing information related to the unpleasantness of pain
Rexed divisions
1952 Rexed subdivided the grey matter of the spinal cord into 10 laminae. Lamina 1–> 5/6 correspond to the dorsal horn
Some of these rexed laminae have special names e.g. lamina II (2) is called substantia gelatinosa
Total pain
Bio-psych-social model +spirtual
Used for palliative care
Overview of first order neurons
Enters the spinal cord through a spinal nerve or the brainstem through the trigeminal nerve
Enters ipsilateral to the peripheral receptor
Remains ipsilateral and synapses with a second order neuron
Overview of second order neuron
Cell body located in the spinal cord/brainstem
It decussates and ascends to the thalamus
Overview of third order neurons
Cell body located within thalamus
Axons project to the somatosensory cortex
What reduces the Nociceptive action potential threshold- hyperalgesia
Bradykinin
Prostaglandin E2
What do the terminals of alpha-delta fibres release
Glutamate
What do the terminals of C fibres release
Glutamate
Substance P
Substance P
Peptide neurotransmitter and vasodilator
Remains bound to receptors for a longer time- causing long-lasting pain
Which channels respond to hot stimuli
TRP channel
Which channels respond to cold stimuli
TRPM8 channels
Mechanical UMN
Respond to excess pressure or mechanical deformation
Respond to incisions that break the skin
Have polymodal characteristics
Chemical UMN
Respond to noxious chemicals
TRP channels modulate the response
Eg capsaicin —> taste spicy foods
Sleeping UMN
Silent type
Only activate if injury has occurred
Response comes with onset of inflammation to the surrounding tissue
Polymodal UMN
Respond to thermal, mechanical and chemical stimuli
Majority found in skin
Analgesia
Selective suppression of pain without effects on consciousness
Anaesthesia
Uniform suppression of pain - no pain felt at all, can cause loss of consciousness
Melzack-Wall pain gate
States that non-painful inputs closes the ‘gate’ to painful inputs, thereby preventing pain sensation from being perceived and felt
A 21 year old student volunteers to take part in a research study investigating the neuropsychology of pain. Awareness of pain is associated with activity in which region of the brain?
Prefrontal cortex
