The pharmacology of analgesics: pain can be extremely debilitating and can cause long
term morbidity.
Analgesics are a group comprised of various classes of medications which provide relief
from pain and are some of the most commonly prescribed medications worldwide.
In this tutorial we will be concerned with the pharmacology of the following analgesics:
Non-steroidal Anti-Inflammatory drugs or NSAIDS, Paracetamol and opioids.
To begin with let’s take a look at a representation of the anatomy and physiology involved in
pain transmission.
Relevant anatomy includes peripheral nerve fibres, the dorsal root ganglion, the spinal
cord, spinothalamic tract, medulla, periaqueductal gray of the midbrain, the thalamus and the
primary somatosensory area of the cerebral cortex.
When trauma occurs at a peripheral site, peripheral nerve fibres are stimulated and an action
potential is stimulated transmitting information about tissue damage along the nerve to the
dorsal root ganglion, eventually synapsing with a second order neuron within the dorsal
horn of the spinal cord in a region called the substantia gelatinosa.
This second order neuron decussates or crosses the spinal cord at this level before entering
the spinothalamic tract and rising through the medulla, periaqueductal gray of the midbrain
and then synapses with a third order neuron within the thalamus.
This third order neuron then continues on, ending at the primary somatosensory region
of the cerebral cortex.
Let’s look at the mechanism by which trauma in peripheral tissues causes this sequence
of events to occur.
Trauma stimulates the enzyme phospholipase A2 to act on phospholipids in the tissue,
metabolizing these to arachidonic acid.
Arachidonic acid is acted on by a number of enzymes, including Cyclo-oxygenase-2 or COX-2
which produces endoperoxides, which are in turn converted in a number of prostaglandins.
These prostaglandins, and other chemical mediators produced due to trauma, cause inflammation
and stimulation of free nerve endings resulting in pain transmission.
However, this process can be interrupted by the use of non-steroidal anti-inflammatory
drugs , or NSAIDs, such as ibuprofen, or by paracetamol which act to block the action
of cyclo-oxygenase-2, providing relief for pain of mild to medium severity.
Another group of medications which block the transmission of pain are opioids.
Opioids, such as morphine, act at opioid receptors at a number of sites to block the transmission
of even severe pain by reducing the amount of neuropeptides and neurotransmitters, such
as Substance P and glutamate, available to continue pain transmission.
Opioid receptors are g protein-coupled receptors, and there are 3 subtypes: delta, kappa and
mew.
When opioids bind to Mew 1 receptors they cause analgesia and are responsible for physical
dependence.
Opioids binding to mew 2 receptors cause many of the side effects associated with opioid
use including respiratory depression, meiosis, euphoria and reduced gastrointestinal motility.
Opioids act at opioid receptors to reduce pain transmission within the substantia gelatinosa
of the dorsal horn of the spinal cord, in the medulla, the thalamus and at the primary
somatosensory region of the cerebral cortex.
In addition to this affect, the binding of opioids to opioid receptors in the periaqueductal
gray of the midbrain causes stimulation of descending inhibitory pathways which acts
to further reduce pain transmission and plays an important part in the analgesic effect
of opioids