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ZICONOTIDE:
Promising New Treatment for Complex
Regional Pain Syndrome (CRPS)
BY LYNN R. WEBSTER, MD AND
KERI L. FAKATA, PHARMD
Ziconotide is a
synthetic neuroactive peptide that
was isolated from a neurotoxin utilized
by the cone shell snail, Conus Magnus,
to capture its prey. It is one of 50,000
peptides isolated from this venom
that has proven to safely and
effectively treat chronic severe
pain in refractory pain patients
who in most cases failed
intrathecal (IT) opioid therapy.
THE FDA APPROVED ZICONOTIDE after a decade of research and
clinical experience in 1,254 patients. Out of this population, 17
were reported to have the diagnosis of CRPS. Eleven of these
patients received ziconotide, and six patients received placebo.
The reported efficacy for this subset of patients was a mean
change in the Visual Analog Scale of Pain Intensity (VASPI) of
25.2 % for patients who received ziconotide, compared to 2.8%
for patients who received placebo (1). One published case report
documented complete resolution of nonambulatory bilateral
lower-extremity CRPS. The patient resumed normal gait after 7
months of treatment and achieved complete resolution with
ongoing of therapy (2). As more experience is gained with the
use of ziconotide, more clinicians are sharing their positive experiences
in treating CRPS at workshops and clinical meetings.
Underlying Mechanisms of Pain in CRPS
IT HAS BEEN PROPOSED that pain in CPRS is neuropathic in
origin, resulting from both peripheral and central sensitization
of somatosensory afferent neurons (3,4). Multiple underlying
mechanisms are responsible for the pain associated with CRPS,
including regional inflammatory reactions, sympathetic maintained
pain, stimulus-independent pain, stimulus-evoked pain,
and peripheral and central sensitization.
Central sensitization may be the mechanism in which
ziconotide is effective for relieving pain and symptoms associated
with CRPS. Transmission of pain from noxious stimuli
results when the stimulated peripheral afferent neurons that
contain A and C fibers transmit nociceptive signals by releasing
chemical signals such as glutamate, aspartate substance P, and
calcitonin gene-related peptide at the spinal cord. These chemical
signals are released at the presynaptic end of the peripheral
neuron in response to an influx of Ca++ into the N-type voltage-sensitive
calcium channel (N-VSCC). These neurotransmitters
activate the dorsal horn neurons in lamina II of the spinal
cord to continue ascending transmission of pain (3,4).
In central sensitization the peripheral afferents spontaneously
fire, resulting in the increased sensitivity of the dorsal
root neuron to input of all forms. In response to inflammation,
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