Physiology of pain 2 Flashcards
Acute vs chronic pain length
Acute = < 3 months
Chronic = > or equal to 3 months
Acute pain
- Causes
- Mechansim
Causes: after surgery, MSK injury, burns
Mechanism
- Inflammatory and nocireceptive due to tissue damage and inflammation
- Peripheral sensitisation
Peripheral sensitisation in acute pain
Leads to hyperalgesia
Reduction in channel threshold at nociceptor ends
- TRPV1
- Na+ channels
Lidocaine
- Type
- Mechanism
Local anaesthetic-
- Sodium channel blockers
- Prevent nociceptor firing
Topical capsaicin treatment
- Mechanism + action
TRPV1 channel agonist
- Repeated use reduces nociceptor firing
Mechanism of action:
- ?Depletes substance P
- Causes peripheral terminals to die back
NSAIDs
- Examples
- Mechanism of action
Aspirin, Ibuprofen
Reduces the inflammatory response by Inhibiting prostaglandin synthesis
- By blocking COX
- Prevents peripheral sensitisation by preventing a decrease in Na+ channel threshold
Paracetamol/acetominophen
- Action
Not NSAID
Inhibits cyclooxygenase (COX) enzymes - But does not reduce inflammation
- Acts on descending serotonergic pathways
Opioids
- Examples
- Mechanism
Examples:
- Morphine
- Codeine
- Tramadol
Mechanism
- Agonists of the endogenous opioid system
- Brainstem = Disinhibition
- Spinal cord
- Peripheral = inhibit channels on nociceptors
Gate control theory
Pain stimulated by nociceptors can be reduced by simultaneous activation of low threshold mechanoreceptors
- Modulates pain at spinal cord level
- Rubbing/ blowing pain can reduce pain sensation
A-beta fibres are stimulates near injury site
- Actives interneurones in dorsal horn [closes gated]
- Inhibits spinothalamic neurones
Chronic pain causes
Inflammatory
- Persistent tissue inflammation
Neuropathic
- Injury to the NS
Neuropathic pain peripheral mechanisms
Peripheral sensitisation
Spontaneous firing of nociceptors
Spontaneous firing of nociceptors
Peripheral mechanism of neuropathic pain.
- Peripheral nerve injury = accumulation of ion channels at regenerating tip of axon
- Increased axonal firing at injury site
Neuropathic pain central mechanisms
Central sensitization
– within spinal cord
Changes in activation patterns/cortical remapping
- within brain
Central sensitization
Increase in the responsiveness of nociceptive neurons within the central nervous system
- Due to reduced threshold of activation for second order neurones
Mechanism for reduced threshold activation in central sensitisation
Similar to LTP:
- Constant firing of axons from the periphery (following injury )= Sustained release of glutamate
- Prolonged depolarisation of the
postsynaptic membrane
= Massive influx of Ca2+ through NMDA receptors - Activation of kinases
= Phosphorylation of NMDA/AMPA receptors - Channel protein synthesis
Central hyperalgesia
After central sensitisation:
- Activation of nociceptors results in amplified spinal cord activation
Central allodynia mechanism
+ Other central sensitisation mechanism
After central sensitisation:
- Non-noxious A-beta fibres sensitised 2nd order neurons [normally the synapse between the fibres are non-functional]
Other mechanisms:
- A-beta fibres form new sprouts that synapse with spinothalamic neurones
- Loss of inhibitory interneurones
Chronic pain treatment
Acute pain treatments could work
Individual patient management is important
Associated symptoms should be treated:
- Depression
- Sleep disturbance
- Fatigue
Tricyclic antidepressants
- Example
- Mechanism
Example: Amitriptyline
Mechanism:
- Acts on descending inhibitory pathways
- Inhibits serotonin and NADR re-uptake.
Anticonvulsant
- Examples
- Mechanism
Examples:
- Gabapentin
- Carbamazepine
Mechanism:
- Reduces spinal cord excitability
- Gabapentin = blocks presynaptic voltage-gated calcium channels
- Prevents glutamate release in nociceptors
- Carbamazepine = blocks Na+ channels
Ketamine
- Type
- Action
- Side effects
Anaesthetic
Mechanism
- NMDA antagonist = reduces glutamate influx
- Prevents second order neurone depolarisation
Side effects:
- Hallucinations
- Nightmares
NICE guideline for treating neuropathic pain
- Amitriptyline or pregabalin/gabapentin
- Switch options in first step or combine the two
- Referral to specialist pain service
- Consider oral tramadol
OR
- Topical lidocaine in combination with second line treatment
Placebo for treating chronic pain
Has be demonstrated to be successful for treating neuropathic pain
Due to activation of descending inhibitory pathways
Complementary alternative therapies for treating chronic pain [5]
Acupuncture
Massage therapy
Homeopathy
Herbal medicine
Hypnosis
