Pain Mechanisms Flashcards
What is defined as chronic pain?
Pain/discomfort persisting continuously/intermittently for >3/12
Describe how pain fibres travel through the dorsal horn.
The nociceptive fibres enter the horn and relay with secondary neurones in either lamina I, II or V
BUT
Lamina II a.k.a. Substantia Gelatinosa (SG)
Is best thought of as a volume control, or regulator
It synapses with lamina I and V to regulate them
Spinothalamic pathways only come out of Lamina I and V
NOT OUT OF LAMINA II
Describe the physiology of the gate control in pain.
Normal route of pain fibres (C and A-delta)
They come into dorsal horn then they synapse with a second order neurone that travels to the thalamus
BUT
There is also the SG that has inhibitory fibres on that synapse, it tonically inhibits it
And SG is regulated by three ways:
- C and A-delta fibres inhibit it
- Mechanoreceptors (A-beta) excite it (So when you rub
or heat an area up this activates these receptors which
increase the SG effect on the synapse and reduce pain)
- Descending inhibitory control from the brain inhibits SG
(Descending inhibitory control also inhibits the synapse directly)
Define hyperalgesia.
Increased pain at normal threshold stimulation
- Thermal or touch
- Results from peripheral and central sensitisation
Define Allodynia.
It means “other pain”
It refers to:
Pain from stimuli which are not normally painful
Pain which occurs other than in the area stimulated
It is not synonymous with referred pain
Describe what is meant by wind up in terms of the pathophysiology of pain.
Tissue injury (nociceptive pain) and nerve damage (neuropathic pain) may cause persistent activation.
Excess Glutamate release, excess NMDA receptor activation, excess 2nd order firing or wind up
Result: long term changes in nociceptive neurones which become hyperexcitable (respond at lower stimulus intensity) … hyperalgesia
Wind up can lead to receptive field expansion at the peripheral site or allodynia
How can chronic pain be classified?
Nociceptive
Mixed
Neuropathic
(visceral)
There are lots of different ways of classification
What is the main point to take away from pain management?
Treat pain well, hard and soon to stop it from progressing to chronic
What is neuropathic pain?
Pain of neuronal origin - very difficult to treat
Cannot be explained by a single disease process or a single specific location of damage
Neuropathy, cancer, trigeminal neuralgia…
Brain/cord/peripheral nerves
Burning
Electric
Tingling - pins and needles
Shooting
(Hyperalgesia and allodynia common)
What can sensitisation after a peripheral nerve injury lead to?
Decreased threshold of the nociceptor to activation
Increased receptive field of nociceptors
Allodynia
Hyperalgesia
Prolonged post stimulus sensations (hyperpathia)
- Sensation outlives actual damage
Emergence of spontaneous activity
Describe some of the pathophysiology of neuropathic pain. (Ectopic)
After damage in the afferent nerve, the part of the nerve beyond the injury upregulates sodium channels and due to inflammation around it starts firing ectopically
Describe some of the pathophysiology of neuropathic pain. (field expansion)
Activation of one damaged nerve makes bundles near also fire
Ephaptic activity.
Describe some of the pathophysiology of neuropathic pain.
Ectopic firing
Field expansion/Ephaptic firing
Along with sensitisation damaged peripheral nerves develop abnormal sodium channels which fire off dysfunctionally and demonstrate different depolarisation properties
After peripheral nerve injury, large afferent sprout dorsally from lamina 3 to lamina 1+2, which gain access to spinal regions involved in transmitting high intensity, noxious signals instead of dealing with low level stimuli.
How can phantom pain present?
Sensation - Non painful - Common Limb pain - Painful neuropathy - Common - Pain in the missing limb
What is CRPS?
Complex Regional Pain Syndrome
Type 1 - no identifiable lesion - after illness
Type 2 - identifiable nerve lesion (Causalgia)
Sympathetically mediated pain or independent
It is a disorder of the extremities
Usually involves a single limb in the early stages
What are some of the causes of CRPS?
CRPS can be triggered by a variety of noxious stimuli Minor trauma Bone fracture Surgery Stroke Myocardial infarct
Idiopathic
What are the signs and symptoms of CRPS?
Sensory
Severe continuous burning pain, hyperalgesia, allodynia
Vasomotor
Temperature asymmetry, skin colour changes, skin colour asymmetry
Sudomotor/Oedema
Oedema, sweating changes or asymmetry
Motor/Trophic
Decreased range of motion, motor dysfunction (weakness, tremor, dystonia), tropic changes (hair, nail, skin)
Describe the mechanism for CRPS.
Original injury initiates a pain impulse carried by sensory nerves to the central nervous system
The pain impulse in turn triggers an impulse in the sympathetic nervous system which returns to the original site of injury
The sympathetic impulse triggers the inflammatory response causing the vessels to spasm leading to swelling and increased pain
The pain triggers another response, establishing a cycle of pain and swelling
What are the stages of CRPS?
Bonica described three stages for CRPS: Stage I - Acute stage Stage II - Dystrophic stage Stage II - Atrophic stage
Describe in detail stage I of CRPS.
Pain in a limb following an event or without apparent cause
Burning or throbbing pain, diffuse aching, sensitivity to touch or cold, localized oedema
The distribution is not compatible with a single peripheral nerve, trunk or root lesion
Vasomotor disturbances occur, producing altered colour and temperature
X-rays are usually normal but may show patchy demineralization of the involved bones
Describe in detail stage II of CRPS.
Stage II is characterized by
Progression of soft tissue oedema
Thickening of the skin and articular soft tissues
Muscle wasting
Development of trophic changes (e.g. skin, nails bone, muscle)
Symptoms typically last for 3-6 months
Describe in detail stage III of CRPS.
Stage III is characterized by: Limitation of movement Contractures of digits Waxy trophic skin changes Brittle ridged nails
X-rays may reveal marked bone demineralization
What are the two causes of cancer pain?
The disease (invasion - neuropathic. visceral, nociceptive, inflammatory) The treatment
What are the treatments available for pain?
Opiates (opium)
NSAIDs, NOADs
What are the effects of opioids?
Analgesia Respiratory depression Nausea and vomiting Antitussive (Stops you coughing) Constipation Itching Euphoria Tolerance and dependence
Tell me a little about opioid receptors.
Three primary subtypes:
- MOP (μ (mu))
- DOP (δ (delta))
- KOP (κ (kappa))
All are G-protein coupled receptors
MOP
Opens K+ channels to hyperpolarise
DOP
Inhibits cAMP
KOP
Close voltage sensitive Ca2+ channels
They all work to inhibit neurotransmitter release
What are the different types of endogenous opioids?
Endomorphins (MOP)
Enkephalins (DOP)
Dynorphins (KOP)
What are some of the sites of opioid action in the pain pathway?
On PAG which is affected by the thalamus and hypothalamus which leads to inhibition of the dorsal horn synapses
On NRPG which leads to inhibition at the dorsal horn synapse via NRM
And directly on the dorsal horn synapse
(And at the periphery)
Not an exhaustive list
Name some weak opioids.
Codeine
Dihydrocodeine
Tramadol
Name some strong opioids.
Morphine Fentanyl Diamorphine Oxycodone Hydromorphone
What is opioid insensitive pain?
Defined as pain that does not respond progressively to increasing opioid dose
Most common causes of this type of pain are
- Nerve compression
- Nerve destruction
The usual pharmacological solutions for neuropathic pain:
- Oral antidepressants
- Anticonvulsants
- Local anaesthetics
With spinal infusions of local anaesthetic and opioid mixtures as the last resort
What are adjuvant analgesics?
An adjuvant is “A pharmacological agent added to a drug to increase or aid its effect”
Adjuvant analgesics are not analgesics in the true sense
But may contribute significantly to pain relief when used either alone or in combination
They are of particular use for opioid-insensitive pain, particularly neuropathic pain
Name some adjuvant analgesics.
NSAIDS Paracetamol Capsaicin Local anaesthetics Cannabinoids ketamine Tricyclics Anticonvulsants and Gabapentin
