mandrake, henbane, and hemlock, among others.
Today’s pharmacopoeia recognizes these sub-
stances as dangerous poisons that have no thera-
peutic applications. Other approaches to pain
relief before the 20th century included ALCOHOL
and the literal “bite the bullet.”
The first pharmaceutical preparation for pain
relief was aspirin, which came into use at the end
of the 19th century. Pharmaceutical preparations
of OPIATESand other pain relievers soon followed.
Dozens of ANALGESIC MEDICATIONSare now available
that can effectively treat and often prevent pain
along the full spectrum of severity.
Breakthrough Research and Treatment Advances
Research in the 1990s provided breakthroughs in
knowledge and understanding of pain mecha-
nisms and, accordingly, for new ways to provide
pain relief. Researchers know, for example, that
women and men experience pain differently, rais-
ing the probability that hormones play a key role
in pain perception and tolerance. There are
genetic factors that come into play as well, such as
the function or dysfunction of the genes that reg-
ulate the production and activity of cytochrome
enzymes. The LIVERproduces these enzymes, such
as CYTOCHROMEP450 (CYP450) ENZYMES, that are
integral to how the body metabolizes numerous
medications, including analgesics. Understanding
pain pathways has helped doctors understand
how analgesics interfere with those pathways,
allowing clinicians to select the analgesics with the
highest likelihood for relieving the pain.
Researchers know, too, that the body releases
numerous biochemicals after injury (traumatic or
surgical) that influence how nociceptors perceive
stimuli. The body also releases biochemicals such
as endorphins and enkephalins that act at the lev-
els of both peripheral nociceptors and central
(spinal cord and brain) neuroreceptors. Research
is under way to develop medications that stimu-
late release of endorphins and enkephalins as well
as to target other mechanisms of the pain pathway
to relieve pain with lowered risk of side effects.362 Pain and Pain Management