Lecture 23 - Pain Flashcards
Three different types of pain
1) Nociceptive - a response to a noxious stimulus
2) Inflammatory - hyperalgesia during inflammation
3) Neuropathic
Acute nociceptive pain
1)
2)
3)
1) Immediate, short duration, localised
2) Activates nervous system
3) Reflex withdrawal response
Example of a nociceptor
Transient potential receptor subunit (An ion channel pore, TPRV1)
Activated by acid, capsaicin, temperature
Inflammatory mediator that is particularly good at inducing hyperalgesia
Prostaglandins
Substances that can lead to hyperalgesia
Histamine, bradykinin, prostaglandin, ATP, 5-HT, H+
Peripheral sensitisation
1)
2)
3)
1) Process of site of injury becoming more sensitive to pain
2) Early inflammation - Amplification of pain by reduction in receptor threshold and reduction in latency
3) Long-term changes - cytokine-, transcription factor-mediated. Leads to increase in number of receptors, neurotransmitters.
Allodynia
Pathological response to a light touch (pain when touched with a feather)
Nerve fibres that transmit pain signals
1)
2)
1) A delta
2) C
A delta-transmitted pain
Fast, sharp, acute, prickling pain.
Mechanical, thermal pain
C-transmitted pain
Slow, aching, throbbing, burning pain.
Chemical pain.
Synaptic receptors most implicated in pain
NMDA, AMPA
Excitatory neurotrasmitters
Glutamate, aspartate
Pain-associated synaptic receptor that has a low threshold
AMPA
Pain-associated synaptic receptor that has a high threshold
NMDA
How is NMDA activated?
Needs enough of a stimulus to remove Mg2+ cap from within ion channel
Effect of opioids
Act presynaptically to decrease neurotransmitter release
Act post-synaptically to hyperpolarise dorsal root neurons
Pain-associated fibres in the spinal cord, descending column
Noradrenergic, 5HT3
Spinal cord target for neuropathic pain
N-type voltage-gated calcium channel receptor.
Definition of chronic pain
Pain that continuous to be present more than three months after surgery or injury
Mutations in which protein can lead to chronic pain?
Sodium channel NaV1.7
Human gene associated with chronic pain
CACNG2 (stargazer gene)
Way to reduce risk of opioid dependence
Multimodal pain management.
Use smaller doses of opioids with other non-opioid analgesic drugs.
Target several parts of the pain pathway
Why can’t opioids be used in pregnant women?
Foetal respiratory depression
Epidural
Inject analgesics into epidural space in spine