Pain Flashcards
What is pain? Why is it important?
An unpleasant sensory or emotional experience, associated with actual or potential tissue damage.
It is important because it promotes avoidance of threatening situations and promotes resting behaviour to enable recovery after injury.
Describe which neurons detect pain
Pain is detected by nociceptors, which are sensory neurons specific to pain. They are everywhere in the body, including the skin and internal organs, and respond to incoming pain stimuli.
They have free nerve endings and synapse in the spinal cord onto ascending neurons projecting up to the brain, where the information is integrated.
Internal and External Pathways Coincide
When we hurt ourselves on our skin, the brain knows exactly where the pain is coming from; however internal nociceptor pathways coincide with external pathways, so the pain is felt externally (on the skin).
Describe the spinal reflex associated with withdrawal from a painful stimulus
Information from nociceptor carried up to spinal cord, where the afferent neuron synapses onto an interneuron, which synapses onto an efferent neuron that causes muscle contraction to pull the body away from the painful stimulus.
What nociceptor receptor is activated when there is intense pressure, stretching, striking or pinching? What does it do?
High threshold mechanoreceptors.
When there is mechanical change, will open ion channels and flux sodium, causing depolarisation and generating an action potential down the nociceptor.
What nociceptor receptor is activated when there is heat, acid or capsaicin? What does it do?
Vanilloid receptors
When activated, open temperature-gated channels (flux sodium, cause action potential down the nociceptor)
What nociceptor receptor is activated when there is tissue damage? What does it do?
Purinergic receptors.
Detect the release of ATP, thus opens channels, causes action potential.
Describe the dual projection into the spinal cord (fast vs slow)
(+ first sensation)
First signal (sensation)
* Activates proprioceptors, which are myelinated and have a large diameter (=very fast)
* Send information about location of sensation
First pain (sharp)
* Activates A delta fibres, which are lightly myelinated and have a medium diameter (=fast; 6-25m/sec)
* Fast localisation of painful stimulus
Second pain (dull)
* Activation of C fibres, which are unmyelinated and have a small diameter (=slow, 1m/sec)
* Stay activated for longer
* Dull, throbbing, continuous ache
* Poorly localised
Describe the dual projection of pain information into the forebrain (sensory information vs emotion)
To the somatosensory cortex via the thalamus
* spinal cord neurons project up to the thalamus, where they synapse and send signals into the somatosensory cortex
* somatosensory cortex is somatotopically organised, so pain is localised
* signals the information about the pain
To the insula and cingulate (‘emotional’ cortex) via the thalamus
* insula and cingulate encode the emotional components of pain (unpleasantness and negative affect)
* signals to stop the pain and protect the body
What are the 2 pain sensitisation processes and the 2 different types of sensitisation?
What kind of sensitisation vs where does the sensitisation happen
- hyperalgesia; noxious stimuli produce exaggerated pain sensation
- allodynia; non-noxious stimuli produce pain sensation
- peripheral sensitisation; inflammatory response in annd around injured tissue
- central sensitisation; neuroplastic changes at synapses in the spinal cord
Describe the process of peripheral sensitisation
(nociceptors becoming hypersensitive to stimulation)
When tissue is damaged, chemicals are released.
In the inflammatory response, neuropeptides (substance P and CGRP) are released from nociceptors and trigger
* vasodilation
* plasma extravasation (leakage of proteins/fluid from capillaries)
* activation of Mast cells and neutrophils
The inflammatory soup:
* histamine
* nerve growth factor
* serotonin
* proteases - cleave extracellular peptide to bradykinin (acts on mechanoreceptors)
* COX enzymes - convert arachidonic acid to prostaglandin (acts on mechanoreceptors)
All these substances cause sensitisation of the nociceptors.
* physphorylation of VR1 receptor lowers its temperature threshold so it opens at a lower temperature
* phosphorylation of sensory nerve specific (SNS) sodium channels lowers its voltage threshold, so the nociceptor is more excitable
Why do we want to increase pain sensitivity?
- act as a reminder that we have hurt ourselves
- so protect injured area to allow recovery without further damage
Some congenital disorders result in no pain perception; these individuals have a lower life expectancy as there are no signals to avoid painful stimuli
Describe the process of central sensitisation
strengthening synapse in the spinal cord due to repeat firing (LTP)
- nociceptor afferents release glutamate and substance P in the spinal cord
- these activate the spinothalamic neurons
- repetitive firing results in neuroplastic changes strengthing the synapse (less stimulation creates larger signal):
- NMDA activation = calcium influx, phosphorylation of AMPA etc. (usual LTP processes)
- substance P activates NK1 receptor; the downstream signalling pathway results in phosphorylation of NMDA and AMPA receptors
- substance P diffuses to other synapses = wind up pain, generalised sensitivity to painful stimuli
Gate Control Theory
or: why it makes sense to hop up and down after stepping on lego
When hopping up and down, rubbing or blowing…..
Stimulation of A alpha/beta fibres (non-nociceptive mechanoreceptors) in the injury region activates the interneuron in the dorsal horn, which inhibits spinothalamic neuron from firing.
Competition between excitation from nociceptor (c fibres) and inhibition from proprioceptor (a fibres)
Prevents pain signals from reaching brain
Distraction; treatment of burns patients
Changing burns dressings can be very painful; opioid treatments can be used but there are issues with dosing and tolerance, addiction etc.
Instead, during the procedure, children are shown a virtual reality environment (snow world) which distracts from the pain.
Reported to reduce pain ratings by 30-50% and less time spent thinking about pain, intensity and unpleasantness.
Hoffman et al. (2004) - evidence of reduced activity in pain processing areas (SSC, anterior cingulate and insula, thalamus) when treatment with VR
Name two internal mechanisms to decrease pain
- distraction
- stress-induced analgesia
Describe the process of stress induced analgesia
Stress induced analgesia is an adaptive response to down-regulate pain.
The central mechanism triggers descending regulation of pain circuitry to inhibit pain signals arriving in the brain
e.g. Endogenous opioid system in the brain that can be activated under stressful circumstances; release of endogenous opioids activates opioid receptors, producing an analgesic (pain-relieving) effect
* evidence: naloxone challenge (opioid antagonist) blocks the analgesic effect
* opioids can inhibit inhibitory neurons in the PAG
Describe how the descending modulatory pain pathway stops pain information from being carried up to the brain
- Glutaminergic projection fires onto opioidergic interneuron in PAG, which releases opioids onto the GABA interneuron, which is inhibited.
- Thus, the serotenergic projection onto the dorsal horn is disinhibited and fires, releasing serotonin into the dorsal horn and activating opioid interneurons
- which inhibit the upstream spinothalamic neuron, so pain information is not carried to the brain.
Can be activated endogenously (stress induced analgesia) or by administering morphine (acts on the opioidergic receptors in different places; same effect)
Describe drugs used to treat acute pain and how they work
Lidocaine (local anaesthetic) - blocks sodium ion channels so no depolarisation
NSAIDs - blocks synthesis of prostaglandin in the inflammatory response, so mechanoreceptors that initiate phosphorylation not activated
Opiate/cannabinoids - activate opioid/cannabinoid receptors leading to inhibition of adenylyl cyclase
Describe how capsaicin can be used to desensitise to pain
e.g. heat pads containing capsaicin
- desensitises receptors so they stop fluxing ions
- causes a massive release of substance P in the spinal cord, resulting in a depletion of substance P which blocks central sensitisation
Describe 4 other methods of activating the endogenous opioid system
- electrical stimulation of PAG; causes clinically significant pain relief, as it stimulates the release of opioids
- acupuncture; similar to gate control theory, some evidence that its effects can be blocked by naloxone, which implicates the opioid system
- placebo; effects can be blocked with naloxone, implicating the opioid system
- non-opioid mechanisms; some stress induced analgesia not blocked by naloxone, implicates other substances - endocannabinoids?
What is neurogenic/neuropathic pain? Give examples
Pain caused by damage to the nerves themselves; from spontaneously discharging nociceptors or lack of inhibitory mechanisms
* shingles
* phantom limb pain
* fibromyalgia
* trigeminal neuralgia
Describe possible mechanisms (peripheral and central) leading to chronic pain
Peripheral
* sensitisation of peripheral neurons
* increased activity of damaged axons and abnormal sprouting
Centrally
* hyperexcitability of central neurons
* reorganisation of synaptic connectivity in spinal cord
* disinhibition (removal of tonic descending inhibitory control)
Management of chronic pain
Chronic pain managment is difficult as it is typically comorbid with a primary disease or mental health condition
80% of depressed people present at the clinic with physical symptoms
Drugs include tricyclic antidepressants, anticonvulsants, NMDA antagonists and cannabinoids
