C H A P T E R 15
Pharmacotherapy of acute orofacial pain
Introduction 349
Modes of Action of NSAIDs 351
Adverse Effects of NSAIDs 351
Efficacy of NSAIDs 356
Paracetamol (Acetaminophen) 363
1. Introduction
The aim of drug therapy for acute orofacial pain is to
relieve pain with maximum efficacy and minimum side
effects. Ideally an analgesic drug provides significant
relief across all pain severities, has minimal side effects,
has few drug interactions and is convenient to administer
(e.g. single daily oral dose, pleasant tasting and rapid
absorption). However, ideal drugs do not exist and when
administering an analgesic consideration should be given
to pain severity, the patient’s medical background,
susceptibility to the various side effects (e.g. gastrointesti-
nal, cardiac, renal) and the fact that patients may differ
genetically in their response to analgesics (Lotsch and
Geisslinger 2006). The orofacial pain practitioner needs
to thoroughly understand the different classes of analge-
sics and their mechanisms of actions and appreciate that
drug actions and interactions change with the patient’s
age and medical status (Kim et al 2004). Analgesics also
have gender-specific adverse events and complex phar-
macological interactions with other medications that the
patient may be taking. This chapter reviews the clinical
pharmacology of drugs usually employed in the treat-
ment of acute orofacial pain. Since long-term nonsteroidal
anti-inflammatory drugs (NSAIDs) and opioids are some-
times employed in the management of persistent or recur-
ring orofacial pain conditions, relevant ‘chronic’ adverse
effects are also discussed.
The pathogenesis of acute and chronic pain involves
peripheral as well as central mechanisms of sensitization
that are associated with plasticity in primary sensory
and dorsal horn neurons (Woolf and Salter 2000). The
local inflammatory response leads to heightened sen-
sitivity and activity of local nociceptors and to distant
effects at the level of the central nervous system (CNS).
A mechanism-based strategy for pain control with
Yair Sharav and Rafael Benoliel
Dipyrone 365
Omega-3 Fatty Acids 365
Opioids 365
Analgesic Drug Combinations 367
Strategy of Pharmacotherapy of Acute Orofacial Pain 370
analgesics should have, at least, three major aims (Camu
et al 2003):
a. Prevention of sensitization of peripheral nociceptors;
b. Interruption of the neuronal transmission of
nociceptive signals; and
c. Attenuation of the nociceptive message in the spinal
cord and other parts of the CNS.
Acute pain is usually activated by an inflammatory
process, so the initial strategy to attain analgesia normally
involves the use of anti-inflammatory drugs. However,
the sole inhibition of inflammation may not be sufficient
to obtain adequate analgesia. NSAIDs, including selective
cyclo-oxygenase enzyme (COX)-2 inhibitors, combine
anti-inflammatory effects with analgesic actions on periph-
eral and central neural targets (Cashman 1996). The clinical
success of NSAIDs has resulted in their widespread use,
and it is estimated that over 30 million patients ingest these
for the treatment of pain and inflammation on a daily basis
(Singh and Triadafilopoulos 1999).
1.1. The Inflammatory ‘Soup’
The ‘inflammatory soup’ is a mixture of bioactive mole-
cules (bradykinin, histamine, prostaglandins, neurotro-
phins and interleukins) produced in response to a variety
of stimuli and tissue injury. These molecules may act per-
ipherally on primary afferents by direct and/or indirect
effects. Direct effects include activation of primary afferent
nociceptors and sensitization of nociceptors that result in
increasing responses to various stimuli. Indirect effects
are mediated by leukocytes and the sympathetic nervous
system. These effects may involve increased excitability
of dorsal horn neurons (DHNs), leading to altered des-
cending pain control mechanisms and adaptive changes
in the thalamus, cortex and higher centres (Millan 1999).