NEW YORKBecause it is so well known that opioids are most
effective for nociceptive pain, they are often ignored when patients
present with neuropathic pain. But opioids are at least as effective
as current agents used for neuropathic pain, Richard Payne, MD, of
Memorial Sloan-Kettering Cancer Center, said at the Third Conference
on Pain Management and Chemical Dependency.
Dr. Payne said that classic teaching tells us that opioids are
more effective against somatic and visceral, or nociceptive pain, and
less so against neuropathic pain, but a neuropathic pain mechanism
does not mean that a patient cannot achieve pain relief with an
opioid. The dose-response curve will be shifted to the right,
merely indicating that higher doses are needed, he observed.
A recent study, Dr. Payne pointed out, showed that patients with pure
neuropathic syndromes such as in diabetic neuropathy and herpetic
neuralgia, experienced equally effective relief from both opioids and
the typically used drugs, eg, gabapentin (Neurontin), tricyclic
antidepressants, and dextromethorphan.
He said that opioids are thought to work by mimicking the action of
endogenous opioid substances like endorphins, dynorphins, and
enkephalins. The drugs bind to receptors found in both the central
and peripheral nervous systems.
The fact that opioids can be administered in a wide variety of doses
and formulationsincluding pills, liquids, capsules,
transmucosal lozenges, suppositories, and subcutaneous, intravenous,
spinal, and intraventricular injectionsincreases their clinical
utility, he said.
The WHO Ladder
Dosing and prescription are dictated by the three-step WHO (World
Health Organization) ladder divided into the categories of mild,
moderate, or severe pain. We are really reliant on the
patients self-report of pain intensity and pain quality,
Dr. Payne noted.
While non-opioid analgesics can reduce mild pain quite well, moderate
or severe pain usually requires an opioid drug in combination with
non-opioid and adjuvant analgesic drug therapy, he said.
The three-step ladder splits opioids into weak and strong drugs. The
weak opioids include codeine, dihydrocodone, hydrocodone, meperidine,
and oxycodone in combination with acetaminophen, aspirin, and/or
caffeine. Although effective in managing mild pain, these weak
opioids are toxic at high doses. As one begins to escalate the
dose to deal with more severe pain, one runs into aspirin,
acetaminophen, and caffeine toxicity as well, he said.
Stronger opioids include hydromor-phone, methadone, morphine,
fentanyl, and oxycodone in its sustained-release form. Because these
agents can be administered at very high doses without concern for
organ toxicity (and with no ceiling to their efficacy), they are
appropriate for moderate or severe pain, Dr. Payne said.
IM Morphine vs Oral Ketoprofen
He cited a clinical trial in which patients with chronic cancer pain
were given oral preparations of ketoprofen, a non-opioid analgesic,
at a dose of 225 mg, or intramuscular morphine at 5 or 10 mg.
Analysis showed mean pain relief over time to be the same for both.
When the dose of the ketoprofen was increased threefold, the patients
failed to show a proportional increase in pain relief. However, 10 mg
of morphine (far from its highest doses) and further dose increases
offered significant pain relief. Doses of morphine ranged from 5 mg
to 35,000 mg, with the majority of patients getting doses from 5 mg
to 699 mg. There is a wide variability in the response to
opioids, but there is no intrinsic ceiling, Dr. Payne said.
The strong opioids are not formulated with acetaminophen, aspirin, or
caffeine. Thus, side effects are limited to those commonly seen with
opioid use, including constipation, nausea, sedation, respiratory
depression, and mental clouding. While 100% of patients will suffer
from constipation, only some will present with the other side
effects, Dr. Payne said.
Constipation can be handled with aggressive and prophylactic
treatment, such as laxatives and stool softeners. Nausea, which
usually subsides on its own, can be eased by changing the opioid or,
as a last resort, by giving an antiemetic. In cases in which optimum
pain relief has been achieved but sedation is a problem, caffeine or
amphetamines can be prescribed.
Because opioids are incompletely cross tolerated and cause adverse
effects with varying severity in different patients, experienced
physicians will change opioids as needed. The presence of
nausea with one drug does not necessarily predict its presence in a
second drug given to the same patient, Dr. Payne said. At
least 80% of chronic pain patients switch opioid treatment once, 44%
at least twice, and 20% switch three or more times.
While tolerance to opioids does occur, side effects typically start
showing before the efficient management of pain diminishes, he said.
For example, respiratory depression, a clinically significant adverse
effect, occurs much faster than tolerance to analgesic effects.
Chronic pain and acute pain require different management techniques.
For chronic pain, Dr. Payne said, transdermal fentanyl (Duragesic)
has become quite popular. It is released across a rate-controlled
membrane for 72 hours, offering noninvasive, continuous, passive
diffusion of the drug across the skin.
However, when a chronic pain patient is faced with breakthrough pain,
there is an acute need for increased analgesia. This is best
dealt with through IV morphine or the new fentanyl lozenges [Actiq],
which when mixed with saliva, penetrate the oral mucosa and reach
therapeutic levels as fast as IV morphine, Dr. Payne said. The
transdermal/lozenge approach to pain management is superior to doses
of morphine administered at intervals, he noted, because the latter
allows blood levels to oscillate in and out of the therapeutic window.
Addiction Fears Unfounded
Unfounded fears that opioid use will lead to tolerance or addiction
continue to impede their efficient use in pain management.
Tolerance and physical dependence do not equate to the
behavioral syndrome we call addiction, he said.
Reduced pain relief with a specific opioid dose, tolerance to opioid
side effects, and physical dependence after withdrawing prolonged
treatment do occur. However, addiction is defined by use without
control, despite harm to the individual, and by compulsive use.
Patients take opioids to treat pain, and in the absence of
pain, we can taper their use, he said.
In the absence of a pre-existing substance abuse disorder, iatrogenic
addiction occurs very rarely when patients are treated with opioids
for pain management. He underscored that although opioid
prescriptions have increased, there has been no evidence of increased abuse.
An ideal analgesic, Dr. Payne said, would provide
pain relief in the absence of anesthesia, provide profound analgesia
that isnt permanent, be easy to administer, be effective
against a variety of types of pain, and have no side effects. Among
the analgesics that are available to physicians today, opiates
fulfill most of these requirements.