Pharmacology
Analgesics
1. Pain
Subjective experience
Direct response to untoward event associated with tissue damage
Nociception – perception of noxious stimuli (damage)
Analgesics - ↓ distress associated with pain, not just antinociceptive
Types:
- Acute – excessive noxious stimulus → intense & unpleasant sensation
- Chronic – aberrations of the normal physiological pathway →
Hyperalgesia - ↑ pain but mild noxious stimulus
Allodyria – pain evoked by non-noxious stimulus
Spontaneous pain – no stimulus
2. Nociceptive afferent pathway
Pain – impulse activity in small diameter primary afferent fibres of peripheral nerves
- C and Aδ fibres each one have sensory endings
C fibres (unmyelinated) – polymodal nociceptive endings
- Convey dull diffuse burning pain
Aδ (myelinated) – convey sharp, well localised pain
3. Activation of nociceptive neurons
Tissue injury causes the release of factors from our tissues (5-
HT, ATP, etc) which bind their respective receptors in the
nerve termini of neurons. These endogenous chemicals either
act directly or enhance the sensitivity to other stimuli (ATP),
generally they act directly. There is a generation of action
potentials which will make their way up the sensor afferent
neuron to the dorsal horn in the spinal cord where it will
synapse and release glutamate which can bind NMDA or
AMPA receptors, both ligand gated ion channels, AMPA have
quicker kinetics but not as permeable to calcium as NMDA
Summary: through the dorsal horn and goes up the spinothalamic tract (ascending pathway) and then it
will reach the brain synapsing in the sensory cortex.
SP, CGRP and ATP increase the sensitivity of the ascending neuron to glutamate
Analgesics
1. Pain
Subjective experience
Direct response to untoward event associated with tissue damage
Nociception – perception of noxious stimuli (damage)
Analgesics - ↓ distress associated with pain, not just antinociceptive
Types:
- Acute – excessive noxious stimulus → intense & unpleasant sensation
- Chronic – aberrations of the normal physiological pathway →
Hyperalgesia - ↑ pain but mild noxious stimulus
Allodyria – pain evoked by non-noxious stimulus
Spontaneous pain – no stimulus
2. Nociceptive afferent pathway
Pain – impulse activity in small diameter primary afferent fibres of peripheral nerves
- C and Aδ fibres each one have sensory endings
C fibres (unmyelinated) – polymodal nociceptive endings
- Convey dull diffuse burning pain
Aδ (myelinated) – convey sharp, well localised pain
3. Activation of nociceptive neurons
Tissue injury causes the release of factors from our tissues (5-
HT, ATP, etc) which bind their respective receptors in the
nerve termini of neurons. These endogenous chemicals either
act directly or enhance the sensitivity to other stimuli (ATP),
generally they act directly. There is a generation of action
potentials which will make their way up the sensor afferent
neuron to the dorsal horn in the spinal cord where it will
synapse and release glutamate which can bind NMDA or
AMPA receptors, both ligand gated ion channels, AMPA have
quicker kinetics but not as permeable to calcium as NMDA
Summary: through the dorsal horn and goes up the spinothalamic tract (ascending pathway) and then it
will reach the brain synapsing in the sensory cortex.
SP, CGRP and ATP increase the sensitivity of the ascending neuron to glutamate
