Intrathecal Ziconotide Antalgic Efficacy for Severe Refractory Neuropathic
Status:
Unknown status
Trial end date:
2021-09-20
Target enrollment:
Participant gender:
Summary
Spinal cord injury (SCI) has an average prevalence of 50 per 100.000 in general population
(30.000 patients with SCI in France) with estimates of the overall prevalence for severe
neuropathic pain ranges from 30 to 51% (up to 10.000 patients in France).
Patients with such spinal lesions may develop neuropathic pain called sublesional pain as
perceived in an area below the level of injury. A second type of pain is at level of injury,
i.e. perceived in a segmental pattern within the dermatome corresponding the spinal cord and
nerve roots. These two types of pain are very harmful and are notoriously difficult to treat
probably because of complex pathogenic mechanisms due to abnormal functioning of deafferented
spinal and supraspinal nociceptive neurons.
Opioids, whatever be the route of administration, had demonstrated their inefficacy for these
patients as well as several surgical techniques. So, chronic pain in relation with spinal
lesion can be defined as real refractory pain.
Synaptic release of neurotransmitters is dependent on calcium intake trough voltage dependent
channels. Type 2.1 or N-Type channels are specific for nociceptive system and can be blocked
by a peptic neurotoxin: Ziconotide. Blocking these specific calcium channels neuromodulates
nociception. Intrathecal use of Ziconotide, bringing the active molecule close to its
receptors, has a proven clinical impact for a wide variety of pain (4). The intrathecal
Ziconotide (ITZ) infusion using an implanted pump is validated for treatment of pain
refractory to systemic analgesics (HAS, avis du 14-27 mai 2008). Meanwhile, no data are
available in literature on positive effects of ITZ on specific spinal neuropathic pain.
A pilot study was performed by the coordinator team using ITZ on 12 patients with spinal
pain: 8 patients had > 40% decrease of pain on numeric scale, 6 patients beneficiated from
implanted pump allowing chronic ITZ treatment inducing 60% numeric scale decrease in average
with 1 year follow-up.
Therefore intrathecal Ziconotide could be an excellent candidate for the treatment of spinal
pain where the pain generators may be difficult to target by other available treatments.
This study is the first to assess ITZ (as IT antalgic monotherapy) versus placebo with a
randomized controlled study with long follow-up. Trials have already been performed but not
specially targeted spinal pain, and did not exceed three weeks follow-up.
Long term effects of Ziconotide on memory, cognition and mood have not been evaluated. In
fact even though short term adverse effects on higher level functions have been described
they have not been assessed in a placebo controlled situation.
Moreover, treating (successfully or not) patients with spinal pain could bring valuable
insights both into the mechanisms of pain production in SCI patients and in the mechanisms of
Ziconotide action: a positive result on pain below the injury level would imply action on the
second or third order synapses of the nociceptive pathways. Similarly an effect at the level
of pain, in absence of an effect below the level pain would argue discussion against such
action. The impact of ITZ on the different clinical components of pain experienced by the
patients, could also give some data on neuromodulation mechanism induced by the therapy.