Page 379 Guide to Pain Management in Low-Resource Settings

Appendix: Glossary 367

Noxious stimulus particular compound is mostly based on economical
A noxious stimulus is one that is damaging to normal and pharmacokinetic considerations (route of admin-
tissues. istration, desired onset or duration, and lipophilicity)
and on side eff ects associated with the respective route
Opioids
of drug delivery. Dosages can vary widely depending on
Opioids act on heptahelical G-protein-coupled recep- patient characteristics, type of pain, and route of admin-
tors. Th ree types of opioid receptors have been cloned istration. Systemically as well as spinally administered
(mu, kappa, and delta). Additional subtypes have been opioids can produce similar side eff ects, depending on
proposed but are not universally accepted. Opioid re- the dosage, with some nuances due to the varying ros-
ceptors are localized and can be activated along all lev- tral (to the brain) or systemic redistribution of diff erent
els of the neuraxis including peripheral and central pro- compounds. Small, systemically inactive doses are used
cesses of primary sensory neurons (nociceptors), spinal in the periphery and are therefore devoid of side eff ects.
cord (interneurons, projection neurons), brainstem, Opioids remain the most eff ective drugs for the treat-
midbrain, and cortex. All opioid receptors couple to G- ment of severe acute and cancer-related chronic pain,
proteins (mainly G /G ) and subsequently inhibit adeny-
i o while they are only a second choice in neuropathic pain
lyl-cyclase, decrease the conductance of voltage-gated and have only a limited indication in chronic noncancer
2+
+
Ca channels and/or open rectifying K channels. Th ese pain that is not neuropathic or infl ammatory. Detrimen-
eff ects ultimately result in decreased neuronal activity. tal side eff ects are usually preventable by careful dose ti-
Opioid peptides are expressed throughout the central tration and close patient monitoring, or they are treated
and peripheral nervous system, in neuroendocrine tis- by comedication (e.g., laxatives) or naloxone. Current
sues, and in immune cells. research aims at the development of opioids with re-
Th e commonly available opioids (e.g., morphine, stricted access to the brain.
codeine, methadone, fentanyl, and their derivatives) are
pure mu-agonists. Naloxone is a nonselective antago- Osteomyelitis pain
nist at all three receptors. Partial agonists must occupy a Infl ammation of the bone due to infection, for ex-
greater fraction of the available pool of functional recep- ample by the bacteria Salmonella or Staphylococcus.
tors than full agonists to induce a response (e.g., analge- Osteomyelitis is sometimes a complication of surgery
sia) of equivalent magnitude. Mixed agonist/antagonists or injury, although infection can also reach bone tis-
(e.g., buprenorphine, butorphanol, nalbuphine, and pen- sue through the bloodstream. Both the bone and the
tazocine) may act as agonists at low doses and as antago- bone marrow may be infected. Symptoms include deep
nists (at the same or a diff erent receptor) at higher doses. pain and muscle spasms in the area of infl ammation,
Such compounds typically exhibit ceiling eff ects for anal- and fever. Especially if the history reveals previous
gesia, and they may elicit an acute withdrawal syndrome surgery in the painful area and pain does not decrease
when administered together with a pure agonist. All opi- with rest in the night, osteomyelitis—especially spon-
oid receptors mediate analgesia but with diff ering side dylodiscitis—should be suspected. Treatment is by bed
eff ects. Mu-receptors mediate respiratory depression, rest, antibiotics, and sometimes surgery to remove in-
sedation, reward/euphoria, nausea, urinary retention, fected bone tissue.
biliary spasm, and constipation. Kappa-receptors medi-
Osteoporosis
ate dysphoric, aversive, sedative, and diuretic eff ects, but
do not mediate constipation. Tolerance and physical de- Th inning of the bones with reduction in bone mass due
pendence occur with prolonged—and eventually short— to depletion of calcium and bone protein. Osteoporosis
administration of all pure agonists. Th us, the abrupt dis- predisposes a person to fractures. Osteoporosis is more
continuation or antagonist administration can result in a common in older adults, particularly postmenopausal
withdrawal syndrome. women, and in patients on steroids. Osteoporosis can
Opioids are eff ective in the periphery (e.g., lead to changes in posture (particularly in the form of a
topical or intra-articular administration, particularly in hunched back known colloquially as “dowager’s hump”)
infl amed tissue), at the spinal cord (intrathecal or epi- and decreased mobility. Often the vertebral body is af-
dural administration), and systemically (e.g., intrave- fected. Pain is usually not constant but temporary and a
nous or oral administration). Th e clinical choice of a symptom of pathological fractures.