Page 45 Guide to Pain Management in Low-Resource Settings

Chapter 6

Pharmacology of Analgesics (Excluding Opioids)

Kay Brune

Th e classes of analgesic drugs mentioned below are How does diclofenac, a member of the class
available worldwide and are constantly replaced by of COX inhibitors, work?
new compounds that are often too costly to be sold in COX inhibitors inhibit peripheral and central hyperal-
all countries. However, pain therapy need not suff er gesia. Like all commonly used analgesic compounds, in-
from this limitation because the essential drugs includ- cluding morphine (an opioid), pregabalin (an antiepilep-
ing cyclooxygenase inhibitors, antiepileptic drugs, opi- tic), ziconotide (an N-type calcium channel blocker), and
ates and opioids, and ketamine are available in almost ketamine (a blocker of the NMDA-receptor-attached
all countries, and the value of the novel compounds re- sodium channel), COX inhibitors exert a major eff ect
mains unclear. in the dorsal horn of the spinal cord (and therefore it
is incorrect to call them “peripheral analgesics”). Com-
Case report 1: Choosing pared to the above drug classes, COX inhibitors have a
the right analgesic distinctly diff erent mode of action. A peripheral trauma
will initiate peripheral hyperalgesia, which results from a
Recently, a good friend of mine drove home on his bi- prostaglandin-induced increase in nociceptor sensitivity.
cycle. He was hit by a car and fell to the ground. Th ere- Also, central hyperalgesia is initiated from the blockade
after, he suff ered from chest pain and asked his doctor of the activity of interneurons due to the production of
for help. He received 10 mg morphine s.c. He called me prostaglandin E (PGE ). Following a peripheral trauma,
2 2
in the middle of the night and told me that the pain was the enzyme COX-2 is expressed in the dorsal horn cells
still devastating, but in addition he felt awful, was nause- by means of hormonal cytokines and neuronal messages.
ated and had vomited. I suggested taking 75 mg diclof- PGE activates protein kinase A (pKA). Th e activation
2
enac resinate. He called the next morning telling me that results in phosphorylation of the glycine-receptor-asso-
he had fallen asleep shortly after having taken diclofenac. ciated chloride channel. Th is, in turn, reduces the prob-
Th is example demonstrates that so-called ability of chloride channel opening. Th e blockade of the
“strong analgesics,” such as morphine and other opioids, chloride channel reduces the hyperpolarization of the
are not always eff ective. In acute musculoskeletal or second neuron and therefore makes it more excitable to
traumatic pain, cyclooxygenase (COX) inhibitors may glutamate-transmitted stimuli. In other words, trauma,
be preferable. A drug like diclofenac (an aspirin-like infl ammation, and tissue damage activate the production
drug) often does a better job. A detailed commentary of COX-2 enzyme in the dorsal horn cells of the spinal
on this case report follows later. cord, which reduces the hyperpolarization of the second
Guide to Pain Management in Low-Resource Settings, edited by Andreas Kopf and Nilesh B. Patel. IASP, Seattle, © 2010. No responsibility is assumed by IASP 33
for any injury and/or damage to persons or property as a matter of product liability, negligence, or from any use of any methods, products, instruction, or
ideas contained in the material herein. Because of the rapid advances in the medical sciences, the publisher recommends that there should be independent
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recommendation by the editors, authors, or IASP in favor of other medical products or procedures that are not covered in the text.