Peripheral nerve blocks provide many benefits for patients, including
superior pain control and reduction in general anesthesia-related side
effects. In order to optimize pain relief while reducing the total dose of
local anesthetic it would be of use to add a drug that both speeds onset and
prolongs sensory blockade or analgesic effect. Improvements in our knowledge
of peripheral nervous system pain mechanisms allow us to develop methods of
prolonging analgesia while reducing central and peripherally mediated
In the last 20 years a number of drugs have been tested, and several
have proven clinically useful when added to local anesthetic for peripheral
nerve block or when used for local infiltration or intraarticular analgesia.
These drugs are known as analgesic adjuvants.
This chapter examines the rationale and current evidence base for use of
analgesic adjuvants and summarizes the best strategies for optimizing pain
control and reducing adverse effects after surgery under peripheral nerve
block, local infiltration, or injection of drugs in the intraarticular
Pain transmission in the central and peripheral nervous systems
involves a complex array of neurotransmitters and pathways that are not
easily blocked by one drug type or technique alone. Involvement of several
classes of neurotransmitter at the injury site, peripheral nerve, dorsal
horn of the spinal cord, and supraspinal sites are responsible for the
transmission of nociception. Use of agonists at inhibitory receptors and
antagonists at excitatory receptors allows a “multimodal” approach with
optimization of pain control and reduction of adverse
In 1645 Descartes proposed a mechanism for pain transmission, suggesting
that a peripheral pain impulse was transmitted directly from the periphery
to the brain by a “hard-wired” system without any intermediate modulation
(Figure 9–1). This theory of pain transmission was widely held as
true until as recently as 40 years ago.
Descartes model of pain transmission in the
peripheral nervous system.
In 1965 Melzack and Wall proposed their groundbreaking gate-control theory
of pain that suggested that pain could be modulated or “gated” at a number
of points in the pain pathway. Subsequent research identified the dorsal
horn (lamina II) of the spinal cord as an important site of potential
modulation, and subsequent treatments for acute and chronic pain have
utilized this knowledge to good effect. Treatments such as the use of spinal
opioids and transcutaneous electrical nerve stimulation (TENS) have both
been developed in the light of this knowledge. The gate theory also changed
many (often unsuccessful) pain management strategies from techniques where
we tried to ablate pain pathways either chemically or surgically to more
recent modulation techniques where we attempt to inhibit excitatory
influences and enhance inhibitory influences within the pain pathway.
In the last few decades important advances have also occurred in our
knowledge of how pain is generated ...