FINISH Pharmacology of pain Flashcards
Pain-definition
An unpleasant sensory & emotional experience associated with actual or potential tissue damage, or described in terms of such damage
Nociception
The neural process of encoding noxious stimuli.
Nociceptor
Definition?
Structure?
Location of cell bodies?
A high threshold sensory receptor, capable of transducing & encoding noxious stimuli
Thinly myelinated Aδ fibres or unmyelinated C fibres. Have ‘free endings’- not specialised.
Activation of a nociceptor is sufficient, but not necessary, for the experience of pain.
Cell bodies located in dorsal root ganglia, trigeminal ganglia for the head.
External stimuli: thermal, mechanical or chemical
Internal stimuli: ATP, bradykinin, acid
Noxious heat- ion channels activated?
Threshold?
TRPV1, TRPM3, anoctamin-1, TRPV2.
Heat sensitive DRG neurones are activated >42 degrees.
Noxious cold- ion channels activated?
TRPM8, TRPA1
Protons- - ion channels activated?
ASICs, TRPV1, TASKS
ATP- ion channels activated?
P2X3
Mechanical stimuli- ion channels activated?
Piezo 1/2, TRPV4?, ASICs?
Sensitization
Characteristic of nociceptors
When a stimulus is great enough to cause tissue damage, response to subsequent stimuli increases.
- hyperalgesia
- allodynia
Hyperalgesia
Increased response to stimuli
Allodynia
Decreased threshold for response
Sensitising agents
Do not directly excite nociceptive nerve terminals but enhance response to excitatory agents
- prostaglandins
- NGF
Agents that both excite & sensitize:
- bradykinin
- ATP
- H+
Neurogenic inflammation
When stimulated, nociceptive nerve terminals release factors that cause vasodilation & increased permeability of blood vessels:
- CGRP
- Substance P
Resulting inflammation or ‘flare’
Neuropathic pain
Peripheral nerve damage can result in pain that often outlasts the initial nerve injury, sometimes indefinitely.
- phantom limb pain
- HIV-associated distal sensory polyneuropathy
- Diabetic neuropathy
- Trigeminal neuralgia
- Postherpetic neuralgia
Opiods
An opiod is a substance producing morphine-like effects that are reversed by antagonists e.g naloxone.
An opiate is a substance found in the opium poppy.
Act by binding to 1 of 4 receptors: μ, κ, δ or ORL1.
Free hydroxyl on the benzene ring & nitrogen atom linked by 2 carbon atoms to the benzene ring are important for activity; bulky substitution of the nitrogen atom introduces antagonist activity.
