Pain And Nociception Flashcards
What is pain?
- an unpleasant sensory and emotional experience associated with actual or potential tissue damage
- it’s subjective and doesn’t need an actual tissue damage
What is pain for? (5)
- alert to tissue damages
- protect injured area
- immobilise
- seek shelter
- promote catabolism (break down energy so can sustain while healing)
What is nociception?
- detection of a stimulus which is potentially tissue damaging
- nociception CAN BE pleasant whereas pain is always unpleasant
- can have pain without nociception or have nociception without pain
- pain is part of nociceptive stimulus
What are the nociceptive primary afferents?
- A delta fibres: characterises first pain= fast onset; C fibres: second pain= slower onset
- C fibres: burning and freezing sensation; A delta fibres: shooting and lancinating
- most nociceptors in sensory ganglion have small cell bodies and contain peptide transmitters
What are the types of cutaneous nociceptors?
- high threshold mechanoceptors, thermal nociceptors, polymodal nociceptors, silent nociceptors
- all above can be innervates by C/ A delta fibres but silent nociceptors mostly for C fibres
What is polymodal nociceptors?
- respond to multiple modalities: Heat and mechanical
What is a capsaicin receptor? (TRPV1)
- found in C fibre terminals, a non selective cation channel
- forms an ion channels can be activated by noxious heat, pH, capsaicin substances
- activation can be further enhanced by inflammatory targets( I.e. The receptor can be activated at a lower threshold to prevent further damages)
- TRPV1 antagonists block noxious heat detection
Why does a burn continue to hurt at room temperature?
- tissue damage results in release of inflammatory mediators and acidification so the threshold to heat is reduced.
- the inflammatory mediators sensitises TRPV1 so it’s now active at a lower temp (ie normal body temp)
What are the changes occurred in the surrounding environment when nociceptors are activated?
- when the nociceptors are activated, axon reflex release CGRP and substance P into blood vessels. = causes flare and oedema.
- In turns, it attract leukocytes (eg mast cell, neutrophils) and release inflammatory mediators e.g. Histamine, 5HT, adenosine, ATP bradykinin, interleukins, substance P
- so increases sensitivity of receptors
Sites of first synapses in nociceptive pathway
- lamina 1,5= both A delta and C fibres; lamina 2= mainly C fibres input
What are the neurotransmitters for nociception?
1- glutamate: binds to AMPA receptor where it has fast excitatory post-synaptic potential (EPSP) effect on 2nd order cell = main synaptic dribe
OR binds to NMDA receptor where it has slow EPSP = summation and potentiation
2-Substance P: binds to Neurokinin 1 receptor where it has slow depolarisation and enhances NMDA receptor activity
= modulatory role and enhance excitation
3- CGRP: binds to CGRP receptor for slow depolartisation = modulatory role and enhance excitation
What are the substances involved in central sensitisation?
- NMDA and substance P
- ie. repeated application of modest stimulus can become enlarge due to increase in sensitisation in central.
- ketamine is a NMDA receptor antagonist so it is an effective analgesic but have side effects= addiction
- substance P antagonists are ineffective as pain therapy management in men
- CGRP antagonists have side effects too
How is nociceptive pathway differ to others’ activity?
- Activation in nociceptive pathways lead to sensitisation, unlike other non-nociceptive pathways where tends to lead to a reduction in their activity.
What is hyperalgesia?
-Increased pain from noxious ( ie normally painful) stimulus, i.e. bigger response than expected
What is allodynia?
- pain evoked by low intensity (usually non-painful stimuli)i.e. sunburnt individuals. Either due to abnormal activity in primary afferents or lowered thresholds in CNS circuits = a neuropathic pain.
Comparison of high and low threshold primary afferents
1) size of cell body: small in high threshold nociceptors; large in low threshold mechanoreceptors
2) fibre class: C fibres in high threshold nociceptors; A-alpha and beta fibres in low threshold mechanoreceptors
3) peptide content: substance P and CGRP in high threshold nociceptors; No substance P and very little CGRP in low threshold mechanoreceptors
4) Only neurogenic inflammation in nociceptors
5) Synapses in lamina: only 1,2 and 5 in nociceptors; 3,4,6 and deeper in low threshold mechanreceptors
What is the gate control theory?
-The gate control theory of pain asserts that non-painful input closes the “gates” to painful input, which prevents pain sensation from traveling to the central nervous system. Therefore, stimulation by non-noxious input is able to suppress pain.
What is the core ascending pathway for nociception?
- Spinothalamic tract
What area of cortex is activated in pain?
- contralateral primary sensory cortex and bilateral association cortex
- Also insular cortex where a person can associate pain by looking at painful events and can activate an autonomic response
- lastly, anterior cingulate cortex where it could potentially code for unpleasantness of the pain.
What are the sub-cortical areas involved in pain?
- hypothalamus, medulla/pons, per-aqueductal gray, parabrachial and amydala
What do the medial nociceptive and lateral nociceptive systems do?
- Medial: affect, attention, cognition, memory response selection
- Lateral: sensory, discriminative, motor coordination
What are the neurotransmitters used in descending control of nociception?
- opioid peptides, serotonin, Na
Where are the major sites of analgesic opioid actions?
1) presynaptic terminals of primary afferent nociceptors: can depress release of glutamate and so reduces synaptic excitation
2) postsynaptically in spinal cord projection neurones: inhibit activity of spinothalamic tract by potassium channel activation and hyperpolarisation
3) periquaductal grey: opioid receptor activation causes activation of PAG projection neurones by inhibiting the tonic synaptic inhibition.
* placebo effect in man is greatly reduced by clockers of opioid recptors
What is projected pain?
- pain arises in a peripheral region due to the affected nerve supplying the region, i.e. sciatic pain in posterior and lateral leg.
- a neuropathic pain
What are de-afferentation pains?
- it is a pain results from interruption of sensory conduction due to damage to touch and pressure fibres= increases sensitivity and irritability of neurones
- phantom limb pain, anaesthesia dolorosa, brachial plexus avulsion injury
- NSAIDS wont help with this kind of pain as it is not caused by inflammation
- characterise with burning, cramping and shooting pain
What is visceral pain?
- usually dull and diffused. Very hard to localised as only C-gibres present in the viscera
- pain can result from stretching of hollow organs (eg. bladder); impaired perfusion and spasm of smooth muscle
- some viscera don’t have nociceptor,e.g. lung, liver, brain, but pain can generate from capsule, peritoneum or meninges
- peritoneum & pleura: visceral layer= innervation from visceral afferent while parietal layer is innervated by somatic afferents
What is referred pain?
- pain perceived at a location other than the site of the painful stimulus, eg. angina pectoralis
- usually there is a convergence between somatic sensory and visceral nerve output, in order to produce a misleading signal
Referred pain in Appendicitis
- pain usually initiated at midline around umbilicus= colon referral
- moves to right in iliac fossa as inflammation of parietal peritoneum (somatic afferents)
- may then generalise again across abdomen with perforation/ peritonitis
