hide
Free keywords:
Opioid, Oxycocone, Restless legs syndrome, pain, pathomechanism, therapy
Abstract:
Opioid receptor agonists are known to relieve restless legs syndrome
(RLS) symptoms, including both sensory and motor events, as well as
improving sleep. The mechanisms of action of opioids in RLS are still a
matter of speculation. The mechanisms by which endogenous opioids
contribute to the pathophysiology of this polygenetic disorder, in which
there are a number of variants, including developmental factors, remains
unknown. A summary of the cellular mode of action of morphine and its
(partial) antagonist naloxone via
alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)
receptors and the involvement of dendritic spine activation is
described. By targeting pain and its consequences, opioids are the
first-line treatment in many diseases and conditions with both acute and
chronic pain and have thus been used in both acute and chronic pain
conditions over the last 40 years. Addiction, dependence, and
tolerability of opioids show a wide variability interindividually, as
the response to opioids is influenced by a complex combination of
genetic, molecular, and phenotypic factors. Although several trials have
now addressed opioid treatment in RLS, hyperalgesia as a complication of
long-term opioid treatment, or opioid opioid interaction have not
received much attention so far. Therapeutic opioids may act not only on
opioid receptors but also via histamine or N-methyl-D-aspartate (NMDA)
receptors. In patients with RLS, one of the few studies investigating
opioid bindings found that possible brain regions involved in the
severity of RLS symptoms are similar to those known to be involved in
chronic pain, such as the medial pain system (medial thalamus, amygdala,
caudate nucleus, anterior cingulate gyrus, insular cortex, and
orbitofrontal cortex). The results of this diprenorphine positron
emission tomography study suggested that the more severe the RLS, the
greater the release of endogenous opioids. Since 1993, when the first
small controlled study was performed with oxycodone in RLS, opioids have
been considered an efficacious off-label therapy in patients with severe
RLS. A recent trial has proved the efficacy of a combination of
prolonged release oxycodone/naloxone in patients with severe RLS as
second-line therapy, with a mean dosage of 10/5 mg twice daily (mean
difference of International Restless Legs Syndrome Study Group Rating
Scale (IRLS) score between groups at 12 weeks: 8.15), and has now been
licensed as the first opioid therapy in Europe. The current results from
both short- and long-term trials and studies with opioids encourage
optimism in alleviating RLS symptoms in patients with severe RLS, or
possibly during or after augmentation. (C) 2016 Elsevier B.V. All rights
reserved.
