Editor's Memo
by Forest A. Tennant, MD, DrPH
 Despite significant, positive
advances in opioid formulations ranging from long-acting tablets to lollipops, the most
potent way to administer opioids is by the intrathecal route. Practical Pain
Management has recently collected and published opioid blood levels from chronic pain
patients throughout the country. One of the striking findings in this survey was that some
patients demonstrated low opioid blood levels even though they were treated with high,
oral dosages of opioids. No wonder. Opioids given by all non-intrathecal routes have a
long, torturous road to reach the endogenous opioid receptors in the central nervous
system. The saliva and gastric juices have the ability to knock out an oral opioid
molecule in the opening round. If an opioid molecule makes it to the small intestine, all
kinds of intraluminal enzymes and gut-wall opioid receptors are well equipped to finish
off an oral opioid—Round 2. If an opioid molecule is lucky enough to reach Round 3,
lots of blood enzymes and and the liver just can’t wait to floor opioid molecules and
send them floating out the bile or urine. Just in case some molecule makes it past the
liver, the goalie of the body, known as the “blood brain barrier,” will deflect
would-be brain seekers “en masse.” All these barriers give credence to estimates
that only one opioid molecule out of a few hundred given orally will reach the innards of
the brain. That is why opioids, to be effective, have to be prescribed in large amounts.
Also, this is the obvious rationale for intrathecal therapy in which essentially 100% of
opioid molecules administered will reach brain targets.
Given that intrathecal administration has the best ability to relieve pain, why
isn’t it more widely utilized? Cost is an obstacle, but so is bias and lack of
knowledge. While no one likes the idea of an implant or its attendant, potential
complications, the effectiveness of intrathecal administration must be recognized and
recommended by all physicians.
From this editor’s position, the underutilization of intrathecal treatment,
including the resistance of third party payors to foot the bill, is the current lack of a
scientific, objective indication for intrathecal therapy. To date, about the only criteria
to implant “the pump” has been a poor response to standard opioid
therapy—whatever that is. It’s time to not only put an end to nebulous clinical
indications, but also to any misdirected claims of unethical, financial gain.
As with all medical advances, science is paving the way. Since the 1950’s,
research on severe pain relative to biologic markers, cardiovascular impacts, and adrenal
hormone abnormalities show that a number of objective biologic assessments are available
to physicians to identify patients who are legitimate, needy candidates for intrathecal
administration. A beginning is to identify patients who state their pain is constant,
unremitting, interferes with sleep and eating, and functionally impairs them without oral
opioid therapy. Then see if the patient has what this editor calls the
“cardiac-adrenal syndrome.” Severe pain is a potent stressor that stimulates the
hypothalamic-pituitary-adrenal axis to increase output of catecholamines and the
glucocorticoids, cortisol, and pregnenolone. These patients demonstrate high resting pulse
rates, often over 100, and abnormal serum adrenal hormone levels which are easily and
inexpensively demonstrated on a single, early morning blood specimen. Serum cortisol may
be high due to the stress of pain but the adrenal gland may exhaust over time and later
show low serum cortisol or low pregnenolone. While excess catecholamine excretion may
cause hypertension, severe pain likely also triggers some central mechanism which raises
blood pressure. Put another way, a simple measure of blood pressure, pulse rate, and serum
pregnenolone and cortisol will demonstrate a “cardiac-adrenal syndrome” in many,
if not, all severe, intractable pain patients. Given the potential hazardous complications
of abnormal adrenal excretion including cardiac arrest, osteoporosis, depression, cerebral
atrophy, and diabetes, among many others, the presence of this syndrome should compel
aggressive pain treatment.
There are other important considerations regarding intrathecal treatment. Too often it
has been billed by advocates as an alternative to oral opioid therapy. This is a fallacy.
Intrathecal therapy should be considered additive and not a substitute for oral therapy.
Seldom can all oral opioid drugs be completely stopped after intrathecal administration is
initiated. There is even some scientific evidence that opioids exert a positive, pain
relieving affect in the periphery. Second, the great pain relieving effect of ziconotide,
which can only be given intrathecally, is a compelling reason to make this route available
to severe pain patients. Ziconotide isn’t the only non-opioid that may be effective
by the intrathecal route. Fortunately, the US has produced some outstanding companies that
are expert in producing a number of opioid and non-opioid medications that are appropriate
for intrathecal use.
How many patients are candidates for intrathecal administration? No one knows for sure,
but epidemiologic surveys of pain incidence and prevalence in the US suggest that one to
three million intractable pain patients may demonstrate a cardiac-adrenal syndrome and
benefit from intrathecal treatment.
—Forest A. Tennant, MD, DrPH
Editor in Chief
— May/Jun 2006
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