Drugs for the Suppression of Pain, Analgesics

Pain Mechanisms and Pathways
Pain is a designation for a spectrum of
sensations of highly divergent character
and intensity ranging from unpleasant
to intolerable. Pain stimuli are detected
by physiological receptors (sensors,
nociceptors) least differentiated morphologically,
viz., free nerve endings.
The body of the bipolar afferent first-order
neuron lies in a dorsal root ganglion.
Nociceptive impulses are conducted via
unmyelinated (C-fibers, conduction velocity
0.2–2.0 m/s) and myelinated axons
(A!-fibers, 5–30 m/s). The free endings
of A! fibers respond to intense
pressure or heat, those of C-fibers respond
to chemical stimuli (H+, K+, histamine,
bradykinin, etc.) arising from tissue
trauma. Irrespective of whether
chemical, mechanical, or thermal stimuli
are involved, they become significantly
more effective in the presence of
prostaglandins.
Chemical stimuli also underlie pain
secondary to inflammation or ischemia
(angina pectoris, myocardial infarction),
or the intense pain that occurs during
overdistention or spasmodic contraction
of smooth muscle abdominal organs,
and that may be maintained by local
anoxemia developing in the area of
spasm (visceral pain).
A! and C-fibers enter the spinal
cord via the dorsal root, ascend in the
dorsolateral funiculus, and then synapse
on second-order neurons in the
dorsal horn. The axons of the second-order
neurons cross the midline and ascend
to the brain as the anterolateral
pathway or spinothalamic tract. Based
on phylogenetic age, neo- and paleospinothalamic
tracts are distinguished.
Thalamic nuclei receiving neospinothalamic
input project to circumscribed areas
of the postcentral gyrus. Stimuli
conveyed via this path are experienced
as sharp, clearly localizable pain. The
nuclear regions receiving paleospinothalamic
input project to the postcentral
gyrus as well as the frontal, limbic
cortex and most likely represent the
pathway subserving pain of a dull, aching,
or burning character, i.e., pain that
can be localized only poorly.
Impulse traffic in the neo- and paleospinothalamic
pathways is subject to
modulation by descending projections
that originate from the reticular formation
and terminate at second-order neurons,
at their synapses with first-order
neurons, or at spinal segmental interneurons
(descending antinociceptive
system). This system can inhibit impulse
transmission from first- to second-
order neurons via release of opiopeptides
(enkephalins) or monoamines
(norepinephrine, serotonin).
Pain sensation can be influenced
or modified as follows:
elimination of the cause of pain
lowering of the sensitivity of nociceptors
(antipyretic analgesics, local
anesthetics)
interrupting nociceptive conduction
in sensory nerves (local anesthetics)
suppression of transmission of nociceptive
impulses in the spinal medulla
(opioids)
inhibition of pain perception (opioids,
general anesthetics)
! altering emotional responses to
pain, i.e., pain behavior (antidepressants
as “co-analgesics,”).