Quality-of-life compromising pain affects at least two-thirds of
individuals with spinal cord injury (SCI). This pain can manifest in
numerous forms, ranging from overuse-related shoulder pain to the
insidious neuropathic pain resulting from nervous-tissue damage.
Recently, this series highlighted a variety of non-pharmaceutical
approaches for reducing SCI pain, in part, because many pain-relieving
drugs have adverse side effects. For example, commonly used opioid drugs
can knock out the body’s production of testosterone, a physiologically
vital hormone that is all ready compromised after SCI.
Testosterone
As discussed elsewhere, testosterone is produced by the testes in men
and, to a lesser degree, the ovaries in women. It promotes the
development of reproductive tissue, sex organs, secondary sexual
characteristics, sexual function, muscle mass/strength, and bone
density. The hormone also helps to maintain neuronal health and inhibits
various post-injury neuron-damaging processes. Testosterone production
is regulated by the secretion of hormones (called gonadotropins) from
the brain’s pituitary. Because it is a central-nervous-system-driven
process, CNS insults like SCI can decrease testosterone levels, often
substantially.
For example, in 2011, investigators at the Milwaukee VA Medical Center
and affiliated institutions demonstrated that 43% of study participants
with chronic SCI had low testosterone levels. Those Individuals
with complete injuries and those taking narcotic pain medications or
opioids were especially affected.
Opioids
Opioids
are molecules that bind to certain receptors on the surface of neurons,
including those in the spinal cord. This binding alters communication
between neurons, in turn, muting pain perception. Isolated from the
poppy, opium is the most well-known example of a naturally occurring
opioid-containing material.
It is the source of many painkilling and substance-abuse drugs, such as
morphine and its derivative heroin. In an effort to tailor specific
neurological responses, numerous synthetic opioids have been created.
In addition, the body produces its own opioid-like molecules, such as the
endorphins associated with the feel-good, endorphin rush or runner’s
high generated by exercise, etc.
Opioids & Pain
Opioids have been extensively used to treat moderate to severe chronic
pain. Although not a panacea, evidence indicates that some opioid drugs
can lessen SCI pain, including morphine, alfentanil, tramadol, fentanyl,
hydromorphone (Dilaudid), methadone, and levorphanol.
Many side effects are associated with opioid use, including sedation,
nausea, dizziness, headaches, dry mouth, mood, vision, and hearing
changes, constipation, bladder dysfunction, and addiction. Considerable
mortality is associated with their use. Specifically, a 2012 article
entitled “Opioid Epidemic in the United States,” noted that there are
now more overdose deaths from opioid pain relievers [My sister became
one of these statistics in 2012.] than deaths from both suicide and car
accidents, or deaths from cocaine and heroin combined. The majority of
these deaths resulted from using opioids exactly as prescribed.
Opioids & Testosterone
An exceedingly important issue is the impact of these drugs on
testosterone levels, especially in a SCI population already suffering
the deleterious effects of compromised testosterone.
Testosterone-depleting effects are often underappreciated by
primary-care physicians, the doctors doing most of the prescribing. In
the case of the most studied opioid morphine, the drug causes a dramatic
reduction in testosterone. Fortunately, once treatment is discontinued,
levels recover.
Scientists speculate that opioids shut-down testosterone production by
inhibiting the release of the brain gonadotropin hormones that stimulate
testosterone production and accelerating the enzymatic degradation of
existing testosterone. So to speak, a wrench has been thrown in the
testosterone assembly line, and the testosterone already in circulation
has been broken down for parts.
Ironically, low testosterone is correlated with increased pain levels.
Hence, if opioids are given to fight pain, the ensuing low testosterone
may actually increase pain.
Because many opioid painkillers are used, it is difficult to
overgeneralize. Furthermore, testosterone-depleting effects are affected
by pharmacological considerations, such as the formulation used, route
of administration, dose, and treatment duration.
Given this problem, experts suggest that testosterone levels be measured
before and periodically after opioid treatment has been initiated.
Finally, it is recommended that those with treatment-induced low
testosterone contemplate testosterone replacement therapy, although this
will not reverse the opioid suppression of the pituitary gonadotropins.
EXPERT OPINION
