Pain Flashcards
Define pain
An unpleasant sensory or emotional experience associated with actual or potential tissue damage - is subjective and personal
How is pain defined?
- Source - somatic, neurogenic, psychological
- Severity - assessed by clinician
- Quality - sharp, dull, aching
- Extent - localised or diffuse
- Duration - intermittent, acute, persistent, chronic
What is the function of pain?
To signal injury/inflammation to promote guarding/resting or learned avoidance
When can pain be pathological?
When it relates to an underlying malignancy and so has no utility
How is peripheral pain detected?
Through noicireceptors which have many subtypes e.g thermal, mechanical and ‘silent’ (only responsive after inflammation!) - DISTINCT NEURON TYPE
Describe the process of pain signalling due to damage of the skin
- Noicireceptor firing projects through spinal cord to cortex
- Inflammatory release of H+, K+, ATP, leukokines and prostoglandins causing sensitization
- Release of substance P and histamine from mast cells cause further sensitization
- Retrograde transport furthers sensitization
What are the fibres that transmit pain?
A delta fibres - sharp, shooting pain (first pain)
C fibres - dull, aching, burning pain (secondary pain)
What is the stucture of the A delta fibers?
- Lightly myelinated
- Small axons
- Conduction of 5-30ms
What is the structure of the C fibers?
- No myelination
- Small diameter
- slow conduction of 0.5-2ms
How can pain perception change following the initial pain?
- Noicireceptors can fire more easily
- “hyperalgesia” where pain becomes more painful
- Allondynia- non-painful stimulus becomes painful
- “silent” nocireceptors become actibe
What is the organisation of the spinal cord?
- Dorsal and ventral roots
- Sensory input goes to dorsal root
- White matter are axon projections, grey matter are cell bodies
- Divided into laminae 1-10 where 1 is dorsal
Where do noicireceptors project into the spinal cord?
- A delta project to laminae 2-3
- C fibres to laminae 1-2
- Laminae 2 is important as it is where first and second pain converges (substantia gelatinosa)
How does the transmission of noicireceptor information differ to other sensory transmission?
- Sends short projections rostrally and caudally in the zone of lissar ipsilaterally
- Then synapse on to zone 2 (substantia gelatinosa) on to second order projection neurons which cross beneath the central canal and ascend contralaterally up the spinal cord (SPINOTHALAMIC TRACT)
Describe the neurochemistry of nocireceptors?
- Release substance P early after injury and glutamate for a fast response at the dorsal horn peripheral laminae (shown with antibodies raised against it)
- Substance P binds to post-synaptic tachykinin receptors (most importantly tachykinin1)
What is the ultrastructure of noiceptor neurons?
2 types of synaptic vesicle
- Large dense core vesicles (LDCV) contain peptides, require more Ca to be released and therefore more action potentials
- Small synaptic vesicles (SSV) contain glutamate
Therefore there is a co-release of substance P and glutamate
How does noiciceptive synapse release change?
- Neurokinin A only released after sensitization
- NOS and NO are also upregulated during pain
What is ‘wind up’ dorsal pain?
- Persistent repetitive activation of C-fibres causes response of dorsal horn to increase progressively
- Dependent however on NMDA activation by glutamate
- CENTRAL SENSITIZATION
What is gate control?
- Mechanosensory stimulation can decrease sensation of pain
- C fibres share tract with A alpha and A beta mechanosensory neurons which activate their own projection neurons and also inhibitory interneurons to the C fibres
What are the different classes of second order neurons within the spinothalamic tract?
Class I - thermal and mechanical stimuli
Class II - have a wide dynamic range
Class III - noiciceptive specific
What is endogenous pain control?
- Mitigates conflict between pain sensation and ability to escape
- Done through PAG located in the midbrain which is activated during excessive pain and sends activation through raphe nuclei to dorsal horn
- Releases enkephalin and endorphins which bind presyaptically to noiciceptors inhibiting Ca2+ and reducing AP length, and post synaptically to dorsal projection neurons to induce hyperpolarisation
What are drugs that control pain referred to as?
Analgesics
What are the classes of analgesics?
- Non-steroidal anti-inflammatory (aspirin)
- Morphine-like drugs (opiods)
- Local anaesthetics (lidocaine/benzocaine)
- Centrally acting non-opiod drugs e.g antidepressants and cannabinoids
note: 95% constitute first 2 categories
How was aspirin discovered?
- Chewing on bark of salix alba had pain relieving properties - contains salicylic acid
- Then synthesis in pure form of acetylsalicyclic acid called aspirin
How does aspirin work?
Targets inflammatory components
- Derived from arachidonic acid which is broken down by COX-1 constantly to produce housekeeping prostoglandins and COX-2 to produce inflammatory prostoglandins
- Aspirin blocks COX-2 (but also a bit of COX-1 and reduces platelet aggregation)
