ArticlePDF Available

Cannabinoids and spinal cord stimulation for the treatment of failed back surgery syndrome refractory pain

Taylor & Francis
Journal of Pain Research
Authors:

Abstract

Objective This study aimed to evaluate pain and its symptoms in patients with failed back surgery syndrome (FBSS) refractory to other therapies, treated with a combination of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), in association with spinal cord stimulation (SCS). Settings Outpatients referred at Pain Unit of San Vincenzo Hospital in Taormina (Italy), between September 2014 and January 2016. Subjects Eleven FBSS patients diagnosed with neuropathic pain using the Douleur Neuropathique 4 questionnaire and suffering from moderate to severe chronic refractory pain, and undergoing treatment with SCS and a combination of THC/CBD for 12 consecutive months. Materials and methods All the included patients discontinued previous unsuccessful therapy at least 2 months before the beginning of the cannabinoid therapy, with the exception of the SCS that was continued. Patients received a fixed dosage of cannabinoid agonists (THC/CBD) that could be increased subjective to pain control response. A Brief Pain Inventory questionnaire was administered to measure pain and its interference with characteristic dimensions of feelings and functions. The duration of treatment with SCS and THC/CBD combination was 12 months. Results Effective pain management as compared to baseline result was achieved in all the cases studied. The positive effect of cannabinoid agonists on refractory pain was maintained during the entire duration of treatment with minimal dosage titration. Pain perception, evaluated through numeric rating scale, decreased from a baseline mean value of 8.18±1.07–4.72±0.9 by the end of the study duration (12 months) (P<0.001). Conclusion The results indicate that cannabinoid agonists (THC/CBD) can have remarkable analgesic capabilities, as adjuvant of SCS, for the treatment of chronic refractory pain of FBSS patients.
© 2018 Mondello et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.
php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work
you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For
permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
Journal of Pain Research 2018:11 1761–1767
Journal of Pain Research Dovepress
submit your manuscript | www.dovepress.com
Dovepress 1761
ORIGINAL RESEARCH
open access to scientific and medical research
Open Access Full Text Article
http://dx.doi.org/10.2147/JPR.S166617
Cannabinoids and spinal cord stimulation for
the treatment of failed back surgery syndrome
refractory pain
Epifanio Mondello¹
Domenico Quattrone²
Luigi Cardia¹
Giuseppe Bova²
Raffaella Mallamace¹
Alessia A Barbagallo²
Cristina Mondello³
Carmen Mannucci³
Martina Di Pietro3
Vincenzo Arcoraci4
Gioacchino Calapai3
1Anesthesia, Intensive Care and
Pain Therapy, Azienda Ospedaliera
Universitaria “G Martino” Messina –
University of Messina, Messina, Italy;
2Pain Therapy Unit, San Vincenzo
Hospital, Azienda Sanitaria Provinciale
Messina, Messina, Italy; 3Department
of Biomedical and Dental Sciences
and Morphofunctional Imaging,
University of Messina, Messina,
Italy; 4Department of Clinical and
Experimental Medicine, University of
Messina, Messina, Italy
Objective: This study aimed to evaluate pain and its symptoms in patients with failed back
surgery syndrome (FBSS) refractory to other therapies, treated with a combination of delta-
9-tetrahydrocannabinol (THC) and cannabidiol (CBD), in association with spinal cord stimula-
tion (SCS).
Settings: Outpatients referred at Pain Unit of San Vincenzo Hospital in Taormina (Italy),
between September 2014 and January 2016.
Subjects: Eleven FBSS patients diagnosed with neuropathic pain using the Douleur
Neuropathique 4 questionnaire and suffering from moderate to severe chronic refractory
pain, and undergoing treatment with SCS and a combination of THC/CBD for 12 consecu-
tive months.
Materials and methods: All the included patients discontinued previous unsuccessful therapy
at least 2 months before the beginning of the cannabinoid therapy, with the exception of the SCS
that was continued. Patients received a fixed dosage of cannabinoid agonists (THC/CBD) that
could be increased subjective to pain control response. A Brief Pain Inventory questionnaire
was administered to measure pain and its interference with characteristic dimensions of feelings
and functions. The duration of treatment with SCS and THC/CBD combination was 12 months.
Results: Effective pain management as compared to baseline result was achieved in all the
cases studied. The positive effect of cannabinoid agonists on refractory pain was maintained
during the entire duration of treatment with minimal dosage titration. Pain perception, evaluated
through numeric rating scale, decreased from a baseline mean value of 8.18±1.07–4.72±0.9 by
the end of the study duration (12 months) (P<0.001).
Conclusion: The results indicate that cannabinoid agonists (THC/CBD) can have remarkable
analgesic capabilities, as adjuvant of SCS, for the treatment of chronic refractory pain of FBSS
patients.
Keywords: cannabinoids, delta-9-tetrahydrocannabinol, THC, cannabidiol, CBD, failed back
surgery syndrome, FBSS, refractory pain, spinal cord stimulation, SCS, cannabis
Introduction
Failed back surgery syndrome (FBSS) is defined by the International Association for
the Study of Pain as “a spinal pain of unknown origin either persisting despite surgical
intervention or appearing after surgical intervention for spinal pain originally in the
same topographical location”.1 Several conditions have been identified as underlying
causes for FBSS, such as epidural fibrosis, global or lateral canal stenosis, foraminal
stenosis, retained disc fragment, recurrent disc herniation or degeneration, spinal
instability, facet joint pain, sacroiliac joint pain, discitis, adhesive arachnoiditis, and
Correspondence: Gioacchino Calapai
Department of Biomedical and Dental
Sciences and Morphofunctional Imaging,
University of Messina, Via Consolare
Valeria 5, 98125 Messina, Italy
Tel +39 090 221 3646
Email gcalapai@unime.it
Journal name: Journal of Pain Research
Article Designation: ORIGINAL RESEARCH
Year: 2018
Volume: 11
Running head verso: Mondello et al
Running head recto: Cannabinoids and SCS for the treatment of FBSS refractory pain
DOI: http://dx.doi.org/10.2147/JPR.S166617
This article was published in the following Dove Press journal:
Journal of Pain Research
Journal of Pain Research 2018:11
submit your manuscript | www.dovepress.com
Dovepress
Dovepress
1762
Mondello et al
others.2 The percentage of the insurgency of chronic pain
after spinal surgery varies significantly ranging from 5% to
74.6%, and the percentage of the need for re-operation is
between 13.4% and 35%.3 Up to 20%–40% of patients who
have undergone lumbar spine surgery experience FBSS.4
Nowadays, this syndrome affects ~0.02%–2% of the general
population.5 The FBSS patients frequently suffer from mod-
erate to severe chronic pain, associated with sensory and/or
motor deficits, as well as other severe chronic pain syndromes
associated with the persistence of low back pain, deteriora-
tion or recurrence of radiculopathy, and sphincter dysfunc-
tion.6,7 The current therapeutic strategies for FBSS include
antidepressant medications, antiepileptic medications,8 deep
brain stimulation, spinal cord stimulation (SCS),9,10 epidural
and intrathecal injections,11,12 spine surgery,13 counseling,14
and exercise therapy.15 FBSS is considered an intractable
syndrome when various combinations of the existing thera-
peutic strategies prove ineffective. Opioids and their major
adjuvants usually produce positive results in the treatment of
chronic pain, especially when other therapeutic approaches
fail. There is an increasing demand for alternative therapeutic
strategies by patients and clinicians when available therapies
are marginally effective, or not well tolerated. In this con-
text, the authors assessed the effectiveness of an alternative
approach for chronic refractory pain associated with FBSS,
using cannabinoids as a multimodal treatment approach to
neuropathic pain. The plant Cannabis sativa L. has been used
for centuries, both for recreational and medicinal purposes.
Only in recent times, studies about exogenous cannabinoids
have been performed to evaluate their therapeutic value
and to investigate the role of endogenous cannabinoids
(endocannabinoids) in physiology and pathophysiology of
many neurologic and neuropsychiatric diseases.16–18 Several
types of insults which can damage the peripheral or central
somatosensory nervous system, including FBSS, can cause
neuropathic pain. It is estimated that 7%–8% of the popula-
tion in developed nations is suffering from neuropathic pain.19
To date, therapeutic options for neuropathic pain induced by
FBSS achieve effective analgesia in only less than 50% of
the cases.20 This pain could, however, be effectively treated
by drugs modulating endocannabinoid system.21 This system
is highly expressed in neurons and immune cells, and it plays
a crucial role in the development of neuropathic pain.22 This
pilot study aimed to evaluate the effect of a combination of
delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) in
FBSS refractory to other available therapeutic strategies,
including opioids, adjuvant drugs, radio frequency neuro-
modulating treatments, and SCS alone. The SCS, a treatment
modality for chronic pain that has been in use since 1967,9 is
an expensive therapy and careful selection for its suitability
is recommended. Remarkable technological advances over
the years have resulted in electrodes transitioning from
single to multi-contact arrays and stimulators from external
radiofrequency coupled to implantable rechargeable devices.
Current implantable SCS electrodes can be inserted per-
cutaneously through a Tuohy needle using essentially the
same technique as that used for an epidural catheter.23 In
this context, a retrospective study documenting the results
obtained with oral administration of cannabinoids agonists,
namely a combination of THC/CBD, in eleven refractory
FBSS patients is presented.
Materials and methods
This article reports a retrospective study, performed at Pain
Therapy Unit of San Vincenzo Hospital of Taormina, in col-
laboration with the Anesthesiology and Pain Therapy Unit
and the Department of Biomedical and Dental Sciences and
Morphofunctional Imaging of the University Hospital “G.
Martino” of Messina. All outpatients included in the study
were referred at the Pain Unit of San Vincenzo Hospital, dur-
ing the period between September 2014 and January 2016.
Treatments were performed in accordance with rules and
ethical standards on human experimentation and the Decla-
ration of Helsinki of 1964 (further revised in 2013). All the
study participants gave written informed consent (including
information on possible risks and side effects) for participa-
tion in the research study. Every precaution was taken to
protect the privacy of patients. The retrospective study was
approved by the Local Ethics Committee (Comitato Etico
Interaziendale della Provincia di Messina) with protocol
number 61/17, and the clinical study is registered with the
number NCT03210766 (www.clinicaltrials.org). Between
November 2014 and December 2015, authors included the
clinical records of eleven FBSS patients suffering from
moderate to severe chronic pain not responsive to other treat-
ment regimens (including neuromodulating techniques), and
considered eligible according to the inclusion and exclusion
criteria established for the study. The patients, aged between
49 and 77 years (median age 61.18±10.26 years), were
equally distributed (six males and five females) (Table 1).
Primary inclusion criteria in this study were the diagnosis of
FBSS refractory to other standard treatments. Patients who
had not discontinued their previous oral analgesic therapy,
at least 2 months before the beginning of the treatment with
cannabinoid agonists, were excluded. The SCS therapy,
unsatisfactory in terms of pain perception as observed from
Journal of Pain Research 2018:11 submit your manuscript | www.dovepress.com
Dovepress
Dovepress
1763
Cannabinoids and SCS for the treatment of FBSS refractory pain
baseline numeric rating scale (NRS) values, was not discon-
tinued (Table 1). Cannabinoid agonists (THC/CBD) were
administered in association with SCS for a treatment period
of 12 consecutive months.
The neuropathic pain was assessed using the Douleur
Neuropathique 4 (DN4) questionnaire in all the cases studied.
The DN4 questionnaire consists of a total of ten items, of
which seven items are related to the characteristics of pain
(burning, painful cold, electric shocks) and its association
with abnormal sensations (tingling, pins and needles, numb-
ness, itching), and three items are related to neurological
examination in the painful area (touch hyperesthesia, pinprick
hyperesthesia, tactile allodynia). The value of 1 was given to
each positive item, and 0 value to each negative item. The
total score was calculated as the sum of all ten items and
the cutoff value for the diagnosis of neuropathic pain was
established as a total score of 4/10.24 Basal DN4 scores of
patients ranged from 7/10 to 10/10 (mean =8.9±1.37). The
Brief Pain Inventory (BPI) allows patients to rate and refer the
severity of their pain and the degree by which pain interferes
with common dimensions of feelings and functions. The BPI
was performed by all the patients both at the first visit and at
the end of treatment (after 12 months). Initially developed
to assess pain related to cancer, the BPI has shown to be
an appropriate measure of pain caused by a wide range of
clinical conditions. The BPI is a eleven-item questionnaire
that consists of four 0–10 NRS items asking patients to rate
their pain at its “worst in the last 24 hours”, “least in the
last 24 hours”, “average”, and “actually”, with 0 indicating
“no pain” and 10 representing “pain as bad as you could
imagine”. The remaining seven BPI items probe the degree
to which pain interferes with general activity, mood, walking
ability, normal work, relations with other people, sleep, and
enjoyment of life, again using a 0–10 value scale. For these
interference items, 0 (zero) represents “does not interfere”
and 10 indicates “interferes completely”.25 Baseline NRS
Table 1 Characteristics of patients, DN4 score, and BPI’s NRS
score before (baseline) and after (nal) treatment with THC/
CBD combination for 12 consecutive months
Patient’s characteristics and questionnaires
Sex (M/F) 6/5
Age range (years) 49–77
Median age (years) 61.18±10.26
DN4 score 8.90±1.37
BPI baseline NRS score (no therapy, only SCS) 8.15±0.98
BPI nal NRS score (SCS and cannabinoid agonists) 4.72±0.9a
Note: aP<0.0001 vs BPI baseline NRS score. Data presented as mean ± SD unless
otherwise indicated.
Abbreviations: DN4, Douleur Neuropathique 4; BPI, Brief Pain Inventory; NRS,
numeric rating scale; SCS, spinal cord stimulation; THC, delta-9-tetrahydrocannabinol;
CBD, cannabidiol.
scores for average pain at visit ranged from 7 to 10 (mean
=8.15±0.98) (Table 1). Patients were visited weekly in the
first month and every 2 weeks for the entire study duration.
All patients received an oleic suspension of THC (19%) and
CBD (<1%), 25 mg/day for oral administration. The dosage
of cannabinoid agonists could be increased, depending on
the positive response to pain control.
Statistical analysis
The numerical data were expressed as the mean ± standard
deviation (SD). For each numerical parameter for basal
observation and after treatment, we separately performed
statistical comparison using the Mann–Whitney test. For
each numerical parameter, considered separately for basal
and final values, we performed a comparison between basal
observation and after treatment to evaluate the existence of
a statistically significant difference using the Wilcoxon test.
Results
In FBSS patients treated with the THC/CBD combination,
an analgesic effect was achieved in four cases within the
first month of treatment. The effect of cannabinoid ago-
nists on refractory pain was maintained during the entire
observation time with minimal dosage titration. The mean
pain perception calculated using the NRS decreased from
8.18±1.07 at first visit to 4.72±0.9 at the end of the obser-
vational time in all cases (Table 2), thus indicating marked
analgesia with the treatment. The THC/CBD combination
significantly reduced burning sensation and paresthesia
linked to FBSS. The BPI interference examination showed
that all the patients reported improvement in the quality of
sleep (11/11; P<0.01). Additionally, THC/CBD combination
enhanced mood as indicated by the rise in baseline mean
level of 5.54±0.52–3.63±0.5 by the end of the study period
Table 2 Brief Pain Inventory in failed back surgery syndrome
(FBSS) among eleven patients treated with spinal cord stimulation
alone, before (baseline) and after (nal) 12 months, and treatment
with THC/CBD, (N=11).
Brief Pain Inventory items Baseline
values
Final
values
Statistics
General activities 6.72±0.90 3.63±0.67 P<0.001
Mood 5.54±0.52 3.63±0.50 P<0.001
Walking abilities 6.45±0.82 3.27±0.78 P<0.001
Normal work 5.90±0.94 3.27±0.46 P<0.001
Relations with other people 6.09±1.04 3.09±0.94 P<0.001
Sleep 6.09±1.44 3.90±1.30 P<0.01
Enjoyment of life 6.18±0.87 3.54±1.03 P<0.001
Note: Data shown as mean ± SD.
Abbreviations: THC, delta-9-tetrahydrocannabinol; CBD, cannabidiol.
Journal of Pain Research 2018:11
submit your manuscript | www.dovepress.com
Dovepress
Dovepress
1764
Mondello et al
(P<0.001). Remarkably, similar results were obtained with
every item on the questionnaire.
The maximum THC/CBD combination dose prescribed
for all patients was 100 mg/day, while the minimum was 50
mg/day, with a mean dose of 68.5 mg/day. All adverse events
were transient lasting from 30 minutes to a few hours, and
not requiring medical care or suspension of therapy (Table 3).
There were no reports of any severe adverse events.
Discussion
FBSS is a symptomatological syndrome, influenced by physi-
cal, psychological, and psychosocial factors that contribute
to worsening individual quality of life. The pathological
mechanism of intractable pain related to FBSS is complex
and includes permanent inflammatory, neuropathic, and
compressive processes, and in some cases are not suscep-
tible to medical or surgical resolution.26 Treatment for this
category of patients aims to achieve relief from pain and
consequently improve quality of life and daily activities.
The diagnosis of FBSS through clinical history or history
of spine operation is not always easy. Physicians should
find the underlying causes of the pain and the mechanisms
responsible for its maintenance and enforcement. Only an
accurate diagnosis can potentially lead to the implementation
of appropriate pain management strategies; this is particu-
larly true for neuropathic pain (of radicular, ganglion, or
spine origin) which is initiated by nervous system lesions
or dysfunction and can be maintained by several different
mechanisms. Moreover, neuropathic pain is more likely to
be caused either by surgical treatment or associated diseases
(comorbidity) and is more difficult to treat than nociceptive
pain.4 Successful treatment outcomes are difficult to achieve
for chronic pain which can, in the long run, adversely affect
the patient, health care services, and eventually the society.
Although SCS can successfully induce analgesia initially,
this has been observed to be relatively temporary, with the
analgesia usually wearing out after 12–24 months,9 as in
the presented study. In this scenario, the quick onset and
prolonged analgesic effects obtained with cannabis-derived
products seem to be independent of the effect of prior SCS
therapy. From the results obtained, the superior analgesia
combined with the low incidence of adverse events suggests
that cannabis-derived products may be a valuable therapeutic
option for chronic refractory pain associated with FBSS, in
comparison to other drug classes including opioids. Canna-
bis-derived products have been used historically for chronic
pain, and are attracting renewed pharmaceutical interest for
analgesia. Epidemiological studies show that 10%–15% of
patients suffering from chronic pain use cannabis to improve
pain, sleep, and mood.18 Cannabinoid compounds mediate
their pharmacological actions by binding to the cannabinoid
receptors, namely cannabinoid type 1 receptor CB1 and can-
nabinoid type 2 receptor CB2. The CB1 receptors are located
predominantly in the nervous system, while CB2 receptors
are present in the immune cells.17 Moreover, several authors
have described cannabinoid neurophysiological system as
distinct but functionally similar to the opioid pain modulation
system.27 Recent clinical trials, investigating the effects of
the newest formulations of synthetic and naturally derived
cannabinoids, demonstrated their analgesic properties for
refractory neurogenic pain, brachial plexus injuries, and
chronic neuropathic pain.16 These studies suggest that the
administration of cannabinoid agonists should be considered
in patients suffering from chronic moderate to severe pain,
especially when other less invasive treatments and opioid
therapies fail, or when extreme adverse events are reported.28
The plant genus Cannabis contains a complex mixture of phy-
tochemicals (over 60 compounds) known as cannabinoids.
Among the cannabinoids, the most investigated are the two
major active chemical constituents, namely THC and CBD.
Cannabinoids are mixed polyketides derived biosynthetically
from malonyl-CoA and hexanoyl-CoA units prenylated with
geranyl phosphate.29 THC is the main psychoactive type of
cannabinoid, whereas CBD is the major component of canna-
bis with a distinct pharmacological and psychotropic profile
to THC. CBD (C21H30O2) is a resorcinol-based compound
devoid of the psychoactive effects of THC and, on the con-
trary, is believed to be able to attenuate the psychotomimetic
effects induced by high dosages of THC. Selective CB2 ago-
nists may reduce central effects, but these are not clinically
available. The mechanism of action of CBD is complex and
Table 3 Adverse events related to treatments
Adverse events Cases (N)
Drowsiness 4
Attention/concentration disorders 3
Dry mouth 2
Headache 2
Nausea/vomiting 2
Apathy 1
Puffy lips 1
Palpitations 1
Dizziness 1
Subjective sense of facial dysmorphism 1
Mood disorders 1
Forgetfulness 1
Increased urinary retention 1
Journal of Pain Research 2018:11 submit your manuscript | www.dovepress.com
Dovepress
Dovepress
1765
Cannabinoids and SCS for the treatment of FBSS refractory pain
not fully known since this molecule is a “multifaceted-target”
drug interacting with several non-endocannabinoid systems
such as receptors, ion channels, enzymes, and transport-
ers.30 CBD modulates the activity of many cellular effectors,
including the receptors CB1 and CB2,31 GPR55,32 5HT1A,33
μ- and δ-opioid,34 peroxisome proliferator-activated receptor
gamma (PPARγ),35 the transient receptor potential subfamily
V member 1 (TRPV1) cation channels,36 and fatty acid amide
hydrolase (FAAH).37
In Italy and other European countries, only a single
product consisting of a THC/CBD oromucosal spray has
been authorized by the regulatory agency for the treatment of
multiple sclerosis spasticity. However, other cannabis flower
preparations may be prescribed for patients suffering from
chronic pain conditions, refractory to conventional therapy.
In the present study, orally administered oleic suspension of
THC (19%) and CBD (<1%) was chosen chiefly because the
pharmacokinetic data indicate that intake of “high content”
of THC cannabis oil results in detectable plasma concentra-
tions of THC as compared to ingestion of “low content”
of THC cannabis oil or “mid-content” THC oil-containing
capsules.38 Additionally, the availability of the product and
the simplicity offered by the oral route of administration for
the oil suspension, in comparison to vaporization, were favor-
able factors in choosing this formulation. Due to the lack of
precise information on efficacy and safety of the product, the
study protocol involved an initial low dosage to be increased
according to the patient response.
In the cases described in the present study, the analysis
of results confirms the positive effects of treatment with
THC/CBD in patients with refractory FBSS pain. More-
over, results from BPI examination show an improvement
in mood and general activities as well (P<0.001). Overall,
THC/CBD combination was well tolerated and not asso-
ciated with any severe side effects. However, the small
number of cases and the lack of a control group are limit-
ing factors for this study to assess a definitive effect and/
or for the identification of patient population for which
treatment with THC/CBD may be appropriate. The posi-
tive effect of THC on the quality of sleep, reported in our
study, has already been observed by other authors,39 and
could perhaps positively influence pain perception. To
the best of our knowledge, this is the first study report-
ing the beneficial effects of a combination of THC/CBD
in FBSS refractory pain. Preliminary studies on cannabis
and sleep suggest that CBD may have therapeutic effects
on insomnia. Similar effects favoring sleep were observed
with THC; however, contradictory findings revealed that
this compound decreases sleep latency and could impair
sleep quality in the long term.40 As a consequence, in our
opinion, the effects of THC on pain may be independent
of an effect on sleep. Finally, cannabis-derived products
should be used cautiously in patients with a history of, or
current anxiety or panic disorder, as well as for those with
potential for reported dependence or abuse. Additionally,
careful monitoring is advised for patients with depression
and other psychiatric disorders.41
Conclusion
This is the first study that underlines the beneficial effects of
cannabinoids for the treatment of FBSS. The results suggest
that THC/CBD combination may represent an innovative
and valid strategy to treat disabling symptoms represented
by pain, nausea, and sleep disorders in FBSS patients. Fur-
thermore, in these patients, cannabinoid treatment could
positively contribute to an improved quality of life. Though
cannabinoids can have common side effects such as dry
mouth and drowsiness, the side effects profile of THC/CBD
combination seems to be milder and well tolerated. The chief
limiting factors of this study are the small number of cases of
FBSS patients with intractable refractory pain and the lack
of a control group, even though it is a general opinion that
interpretation of results obtained with placebo-controlled
trials may encounter difficulties because of the psychoactive
effects of cannabis. Additionally, it must be noted that ethical
rules in Italy are very restrictive, especially in the context
of pain treatment.
Albeit the limitations, in all the cases reported, the
beneficial effect obtained with cannabinoids in association
with SCS demonstrate that SCS therapy alone may be not
sufficient to provide adequate analgesia.
Finally, we believe that prospective clinical studies are
required to assess the real safety and efficacy of THC/CBD
combination for chronic FBSS refractory pain. In conclu-
sion, the current study suggest that THC/CBD combination
represents an alternative treatment strategy in FBSS patients
with chronic and severe pain, refractory to neuromodulating
techniques, and is a valuable adjuvant to SCS.
Acknowledgment
Authors presented an earlier version of the abstract as a poster
at the 38th Italian Society of Pharmacology (SIF) National
Meeting in Rimini (Italy) in October 2017, prior to the actual
completion or publication of the work.
Journal of Pain Research 2018:11
submit your manuscript | www.dovepress.com
Dovepress
Dovepress
1766
Mondello et al
Author contributions
All authors made substantial contributions to conception and
design, acquisition of data, or analysis and interpretation of
data; took part in drafting the article or revising it critically
for important intellectual content; gave final approval of the
version to be published; and agree to be accountable for all
aspects of the work.
Disclosure
The authors report no conflicts of interest in this work.
References
1. Harvey AM. Classification of chronic pain – descriptions of chronic pain
syndromes and definitions of pain terms. Clin J Pain. 1995;11(2):163.
2. Slipman CW, Shin CH, Patel RK, et al. Etiologies of failed back surgery
syndrome. Pain Med. 2002;3(3):200–214.
3. Hussain A, Erdek M. Interventional pain management for failed back
surgery syndrome. Pain Pract. 2014;14(1):64–78.
4. Thomson S. Failed back surgery syndrome – definition, epidemiology
and demographics. Br J Pain. 2013;7(1):56–59.
5. Peul WC, van Houwelingen HC, van den Hout WB. Leiden – the Hague
Spine Intervention Prognostic Study Group. Surgery versus prolonged
conservative treatment for sciatica. N Engl J Med. 2007;356:2245–2256.
6. Chan CW, Peng P. Failed back surgery syndrome. Pain Med.
2011;12(4):577–606.
7. Baber Z, Erdek MA. Failed back surgery syndrome: current perspec-
tives. J Pain Res. 2016;9:979–987.
8. Prochazka J. T215 effect of gabapentin on neuropathic pain in failed
back surgery syndrome. Eur J Pain Suppl. 2011;5(1):40.
9. Abeloos L, de Witte O, Riquet R, Tuna T, Mathieu N. Évaluation à long
terme de la stimulation médullaire dans les douleurs lombosciatiques
neuropathiques postopératoires : étude rétrospective. [Long-term
outcome of patients treated with spinal cord stimulation for therapeuti-
cally refractory failed back surgery syndrome: a retrospective study].
Neurochirurgie. 2011;57(3):114–119. French.
10. Kumar K, North R, Taylor R, et al. Spinal cord stimulation vs. conven-
tional medical management: a prospective, randomized, controlled,
multicenter study of patients with failed back surgery syndrome
(PROCESS Study). Neuromodulation. 2005;8(4):213–218.
11. Demartini L, Stocco E, Bonezzi C. Failed back surgery syndrome and
intrathecal drugs infusion. Eur J Pain Suppl. 2010;4(S4):299–301.
12. Kumar K, Hunter G, Demeria DD. Treatment of chronic pain by using
intrathecal drug therapy compared with conventional pain therapies: a
cost-effectiveness analysis. J Neurosurg. 2002;97(4):803–810.
13. Duggal N, Mendiondo I, Pares HR, et al. Anterior lumbar interbody
fusion for treatment of failed back surgery syndrome: an outcome
analysis. Neurosurgery. 2004;54(3):636–644.
14. Esmer G, Blum J, Rulf J, Pier J. Mindfulness-based stress reduction
for failed back surgery syndrome: a randomized controlled trial. J Am
Osteopath Assoc. 2010;110(11):646–652.
15. Mathews M, Mazhuvanchery C, Rab F. (562) Post laminectomy syn-
drome: treatment outcomes from a pain rehabilitation program. J Pain.
2014;15(4):S116.
16. Lynch ME, Campbell F. Cannabinoids for treatment of chronic non-
cancer pain: a systematic review of randomized trials. Br J Clin Phar-
macol. 2011;72(5):735–744.
17. Mannucci C, Navarra M, Calapai F, et al. Neurological aspects of medi-
cal use of cannabidiol. CNS Neurol Disord Drug Targets. 2017;16(5):
541–553.
18. Torrance N, Smith BH, Bennett MI, Lee AJ. The epidemiology of
chronic pain of predominantly neuropathic origin. Results from a
general population survey. J Pain. 2006;7(4):281–289.
19. Attal N, Bouhassira D. Pharmacotherapy of neuropathic pain: which
drugs, which treatment algorithms? Pain. 2015;156(Suppl 1):S104–S114.
20. Finnerup NB, Sindrup SH, Jensen TS. The evidence for pharmacological
treatment of neuropathic pain. Pain. 2010;150(3):573–581.
21. Lynch ME, Ware MA. Cannabinoids for the treatment of chronic non-
cancer pain: an updated systematic review of randomized controlled
trials. J Neuroimmune Pharmacol. 2015;10(2):293–301.
22. Maldonado R, Baños JE, Cabañero D. The endocannabinoid system
and neuropathic pain. Pain. 2016;157(Suppl 1):S23–S32.
23. Foletti A, Durrer A, Buchser E. Neurostimulation technology for the
treatment of chronic pain: a focus on spinal cord stimulation. Expert
Rev Med Devices. 2007;4(2):201–214.
24. Attal N, Perrot S, Fermanian J, Bouhassira D. The neuropathic compo-
nents of chronic low back pain: a prospective multicenter study using
the DN4 Questionnaire. J Pain. 2011;12(10):1080–1087.
25. Atkinson TM, Rosenfeld BD, Sit L, et al. Using confirmatory factor
analysis to evaluate construct validity of the brief pain inventory (BPI).
J Pain Symptom Manage. 2011;41:558–565.
26. Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors
and prevention. Lancet. 2006;367(9522):1618–1625.
27. Pertwee RG. Targeting the endocannabinoid system with cannabi-
noid receptor agonists: pharmacological strategies and therapeutic
possibilities. Philos Trans R Soc Lond B Biol Sci. 2012;367(1607):
3353–3363.
28. Ware MA, Doyle CR, Woods R, Lynch ME, Clark AJ. Cannabis use
for chronic non-cancer pain: results of a prospective survey. Pain.
2003;102(1–2):211–216.
29. Stout SM, Cimino NM. Exogenous cannabinoids as substrates, inhibi-
tors, and inducers of human drug metabolizing enzymes: a systematic
review. Drug Metab Rev. 2014;46(1):86–95.
30. Fernández-Ruiz J, Sagredo O, Pazos MR, et al. Cannabidiol for neu-
rodegenerative disorders: important new clinical applications for this
phytocannabinoid? Br J Clin Pharmacol. 2013;75(2):323–333.
31. Hayakawa K, Mishima K, Hazekawa M, et al. Cannabidiol potentiates
pharmacological effects of delta(9)-tetrahydrocannabinol via CB(1)
receptor-dependent mechanism. Brain Res. 2008;1188:157–164.
32. Ryberg E, Larsson N, Sjögren S, et al. The orphan receptor GPR55 is a
novel cannabinoid receptor. Br J Pharmacol. 2007;152(7):1092–1101.
33. Russo EB, Burnett A, Hall B, Parker KK. Agonistic properties of can-
nabidiol at 5-HT1a receptors. Neurochem Res. 2005;30(8):1037–1043.
34. Kathmann M, Flau K, Redmer A, Tränkle C, Schlicker E. Cannabidiol
is an allosteric modulator at mu- and delta-opioid receptors. Naunyn
Schmiedebergs Arch Pharmacol. 2006;372(5):354–361.
35. Esposito G, Scuderi C, Valenza M, et al. Cannabidiol reduces
Aβ-induced neuroinflammation and promotes hippocampal neurogen-
esis through PPARγ involvement. PLoS One;20111(6):e28668.
36. Costa B, Giagnoni G, Franke C, Trovato AE, Colleoni M. Vanilloid
TRPV1 receptor mediates the antihyperalgesic effect of the nonpsycho-
active cannabinoid, cannabidiol, in a rat model of acute inflammation.
Br J Pharmacol. 2004;143(2):247–250.
37. Bisogno T, Hanus L, de Petrocellis L, et al. Molecular targets for can-
nabidiol and its synthetic analogues: effect on vanilloid VR1 receptors
and on the cellular uptake and enzymatic hydrolysis of anandamide.
Br J Pharmacol. 2001;134(4):845–852.
38. Goodwin RS, Gustafson RA, Barnes A, Nebro W, Moolchan ET, Huestis
MA. Delta(9)-tetrahydrocannabinol, 11-hydroxy-delta(9)-tetrahydro-
cannabinol and 11-nor-9-carboxy-delta(9)-tetrahydrocannabinol in
human plasma after controlled oral administration of cannabinoids.
Ther Drug Monit. 2006;28(4):545–551.
39. Blumenthal DE, Malemud CJ. Recent strategies for drug development in
fibromyalgia syndrome. Expert Rev Neurother. 2016;16(12):1407–1411.
40. Babson KA, Sottile J, Morabito D, Cannabis MD. Cannabis, can-
nabinoids, and sleep: a review of the literature. Curr Psychiatry Rep.
2017;19(4):23.
41. Clark AJ, Lynch ME, Ware M, Beaulieu P, Mcgilveray IJ, Gourlay D.
Guidelines for the use of cannabinoid compounds in chronic pain. Pain
Res Manag. 2005;10(Suppl A):44A–46A.
Journal of Pain Research 2018:11 submit your manuscript | www.dovepress.com
Dovepress
Dovepress
Journal of Pain Research
Publish your work in this journal
Submit your manuscript here: https://www.dovepress.com/journal-of-pain-research-journal
The Journal of Pain Research is an international, peer reviewed, open
access, online journal that welcomes laboratory and clinical findings
in the fields of pain research and the prevention and management
of pain. Original research, reviews, symposium reports, hypoth-
esis formation and commentaries are all considered for publication.
The manuscript management system is completely online and includes
a very quick and fair peer-review system, which is all easy to use. Visit
http://www.dovepress.com/testimonials.php to read real quotes from
published authors.
Dovepress
1767
Cannabinoids and SCS for the treatment of FBSS refractory pain
... This review included 5 case reports (2 abstracts) [35][36][37][38][39], 4 retrospective cohort studies [40][41][42][43], 1 prospective cohort study [44], 1 observational cross-over study [45] (study where all participants receive the same two or more treatments), and 1 RCT [46]. Only four studies had a comparison or control group: Bebee et al.'s [46] RCT control, Vigil et al. [41] had patients from the same rehabilitation clinic, Yassin et al. [45] had the experimental group serve as their own control, and Takakuwa et al. [40] made comparisons across experimental groups of differing opioid users. ...
... Haroutounian et al.'s study [44] had an intervention of prescribed cannabis dose of 20 g/month with the option of smoked, baked cooked, or olive oil extract drops. Mondello et al. [42] was a THC to CBD ratio oleic suspension, but the exact amount of THC or CBD was not monitored. ...
... The RCT [46] had a follow-up time of 2 h. The retrospective studies [40][41][42][43] ranged from 12-week follow-up time to retrospectively measuring up to 11 years. The cross-over study, Yassin et al. [45], was 6 months of follow-up time. ...
Article
Full-text available
This systematic review aims to inform the current state of evidence about the efficacy and effectiveness of medical cannabis use for the treatment of LBP, specifically on pain levels and overall opioid use for LBP. Searches were conducted in MEDLINE (PubMed), Embase, and CINAHL. The search was limited to the past 10 years (2011-2021). Study inclusion was determined by the critical appraisal process using the Joanna Briggs Institute framework. Only English language articles were included. Participant demographics included all adult individuals with LBP who were prescribed medical cannabis for LBP and may be concurrently using opioids for their LBP. Study quality and the risk of bias were both evaluated. A narrative synthesis approach was used. A total of twelve studies were included in the synthesis: one randomized controlled trial (RCT), six observational studies (one prospective, four retrospective, and one cross-over), and five case studies. All study results, except for the RCT, indicated a decrease in LBP levels or opioid use over time after medical cannabis use. The RCT reported no statistically significant difference in LBP between cannabis and placebo groups. Low back pain (LBP) affects 568 million people worldwide. In the United States, LBP treatment represents more than half of regular opioid users. With the opioid epidemic, alternative methods, particularly medical cannabis, is now increasingly sought by practicing physicians and patients. Due to its infancy, there is minimal high-quality evidence to support medical cannabis use as a first line treatment for LBP.
... Fourteen other studies explicitly stated that all cannabis use, whether for medical or non-medical purposes, was evaluated [4, 97, 100, 104, 106, 108-110, 112, 116, 132, 135, 138, 144]. Fifteen NRSs focused strictly on medical use, overseen by a physician [94,98,99,101,111,120,121,131,133,136,148,149,152,156,158]; four focused strictly on non-prescribed medical use (i.e., taken for a perceived or actual medical condition, not for recreational purposes) [150,151,154,155]; and ten focused strictly on non-medical/recreational use [93,114,125,129,130,137,147,153,162]. The remaining NRS studied medical use of any kind [140]. ...
... Additional stand-alone conditions and indications. Six RCTs [20,61,73,81,84,92], five cohort studies [121,136,137,145,159], and one cross-sectional study [141] evaluated the effects of cannabis use on a variety of other patient conditions and indications and reported a mix of findings. ...
... • Failed back surgery syndrome (pain scores, sleep, mobility, physical health symptoms, QoL, social functioning, and mood; cohort study, unadjusted findings) [136] and • Older adults with sedentary lifestyles (BMI; cohort study, adjusted findings) [159]. ...
Article
Full-text available
Background Cannabis legalization has enabled increased consumption in older adults. Age-related mental, physical, and physiological changes may lead to differences in effects of cannabis in older adults compared to younger individuals. Objective To perform a scoping review to map the evidence regarding the health effects of cannabis use for medical and non-medical purposes in older adults. Methods Electronic databases (MEDLINE, Embase, PsycINFO, Cochrane Library) were searched for systematic reviews (SRs), randomized controlled trials (RCTs) and non-randomized/observational studies (NRSs) assessing the health effects and associations of cannabis use (medical or non-medical) in adults ≥ 50 years of age. Included studies met age-related inclusion criteria or involved a priori identified health conditions common among older adults. Records were screened using a liberal accelerated approach and data charting was performed independently by two reviewers. Descriptive summaries, structured tables, effect direction plots and bubble plots were used to synthesize study findings. Findings From 31,393 citations, 133 publications describing 134 unique studies (26 SRs, 36 RCTs, 72 NRSs) were included. Medical cannabis had inconsistent therapeutic effects in specific patient conditions (e.g., end-stage cancer, dementia), with a number of studies suggesting possible benefits while others found no benefit. For medical cannabis, harmful associations outnumbered beneficial, and RCTs reported more negative effects than NRSs. Cannabis use was associated with greater frequencies of depression, anxiety, cognitive impairment, substance use and problematic substance use, accidents/injuries, and acute healthcare use. Studies often were small, did not consistently assess harms, and did not adjust for confounding. Discussion The effects of medical cannabis are inconsistent within specific patient conditions. For older adults, generally, the available evidence suggests cannabis use may be associated with greater frequencies of mental health issues, substance use, and acute healthcare use, and the benefit-to-risk ratio is unclear. Studies with a balanced assessment of benefits and harms may guide appropriate public health messaging to balance the marketing pressures of cannabis to older adults.
... 64 In our review, we identified 14 studies investigating chronic neuropathic pain in a total of 506 patients. [65][66][67][68][69][70][71][72][73][74][75][76][77][78] Seven studies reported satisfactory results, 65-71 1 study showed unfavorable results, 72 and the remaining 6 studies reported inconsistent results after treatment with THC and CBD. [73][74][75][76][77][78] Table 6 presents the list of studies on chronic neuropathic pain. ...
Article
Full-text available
Chronic pain affects up to 40% of adults, contributing to high medical expenses, the loss of productivity, reduced quality of life (QoL), and disability. Chronic pain requires detailed diagnostic assessment, treatment and rehabilitation, yet approx. 80% of patients report inadequate pain management. As new treatment options are needed, we aimed to explore the effectiveness of medical cannabis-based products in managing chronic pain, with a particular focus on treatment patterns.We searched the PubMed, Scopus and Web of Science databases using keywords related to cannabinoids and chronic pain syndromes. In total, 3,954 articles were identified, and 74 studies involving 12,562 patients were included. The effectiveness of cannabis-based products varied across studies. Cannabinoids were most effective in treating chronic secondary headache and orofacial pain, chronic secondary musculoskeletal pain, chronic secondary visceral pain, and chronic neuropathic pain. Properly qualifying patients is the first crucial step in managing chronic pain, considering pain characteristics, comorbidities and other treatment options. Treatment should start with low doses of cannabinoids, which are then increased to achieve the desired therapeutic effect while minimizing adverse effects.This narrative review revealed significant gaps in the evidence regarding precise treatment patterns, particularly for the long-term maintenance treatment needed by patients with chronic pain. Medical cannabis can be considered an option for carefully selected patients with chronic pain syndromes when other treatment options fail to achieve an adequate response, and when the potential benefits outweigh the risks. However, there is still a need for well-designed clinical research to establish the long-term efficacy and safety of cannabinoids.
... Effective pain control was achieved in all treated patients, and the effect was maintained throughout the treatment period. Pain was rated using a numerical rating scale and decreased from a mean baseline value of 8.18 ± 1.07 to 4.72 ± 0.9 after 12 months of treatment (p < 0.001) [67]. ...
Article
Full-text available
Introduction and objective: Low back pain (LBP) is a major cause of disability and the main reason why individual patients need medical attention. Pharmacological treatment options for LBP are limited and are often associated with serious side-effects. This makes it necessary to search for new painkillers. One potential therapeutic agent is cannabidiol (CDB). Cannabidiol and tetrahydrocannabinol are the most researched components of cannabis, the plant more commonly known as marijuana or hemp. To the best of our knowledge, this is the first narrative review of the effects of CBD alone on acute and chronic back pain. Review methods: Based on the guidelines provided by the Primary Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA), the PubMed/ MEDLINE database was used to identify articles for analysis from the last 30 years. Due to the limited number of studies on this topic, all types of studies that met the inclusion criteria were included. After analysis, 10 studies were included in this review. Brief description of the state of knowledge: Currently, the use of medical marijuana continues to increase and the Food and Drug Administration (FDA) has already approved four cannabis-based drugs. Cannabidiol (CBD) is a relatively safe substance for humans and generally well tolerated. It is a substance that is easily available and often taken by patients with LBP. Summary: Evidence for the effectiveness of CBD in the treatment of acute low back pain is lacking. There was only one clinical trial conducted in the Emergency Department that showed no superiority of CBD over placebo in acute LBP. The majority of studies concern chronic rather than acute LBP. Although most of the results suggest a beneficial effect of cannabinoids in relieving chronic LBP, hard evidence is lacking. Rigorous randomized controlled trials are needed.
... Literature has reported the incidence of FBSS in up to 40% of the cases (Alizadeh and Sharifzadeh, 2021). Disabling neuropathic pain usually persists or worsens with time and dramatically affects quality of life (Mondello et al., 2018). When other therapies have failed, treatment paradigms resort to spinal cord stimulation (SCS), which provides electric therapy through implanted electrodes for pain relief (Alizadeh and Sharifzadeh, 2021;Hosseini et al., 2021). ...
Article
Full-text available
Failed back surgery syndrome (FBSS), a chronic neuropathic pain condition, is a common indication for spinal cord stimulation (SCS). However, the mechanisms of SCS, especially its effects on supraspinal/brain functional connectivity, are still not fully understood. Resting state functional magnetic resonance imaging (rsfMRI) studies have shown characteristics in patients with chronic low back pain (cLBP). In this case study, we performed rsfMRI scanning (3.0 T) on an FBSS patient, who presented with chronic low back and leg pain following her previous lumbar microdiscectomy and had undergone permanent SCS. Appropriate MRI safety measures were undertaken to scan this subject. Seed-based functional connectivity (FC) was performed on the rsfMRI data acquired from the FBSS subject, and then compared to a group of 17 healthy controls. Seeds were identified by an atlas of resting state networks (RSNs), which is composed of 32 regions grouped into 8 networks. Sliding-window method and k-means clustering were used in dynamic FC analysis, which resulted in 4 brain states for each group. Our results demonstrated the safety and feasibility of 3T MRI scanning in a patient with implanted SCS system. Compared to the brain states of healthy controls, the FBSS subject presented very different FC patterns in less frequent brain states. The mean dwell time of brain states showed distinct distributions: the FBSS subject seemed to prefer a single state over the others. Although future studies with large sample sizes are needed to make statistical conclusions, our findings demonstrated the promising application of dynamic FC to provide more granularity with FC changes associated with different brain states in chronic pain.
Article
Synthetic cannabinoids are compounds made in the laboratory to structurally and functionally mimic phytocannabinoids from the Cannabis sativa L. plant, including delta-9-tetrahydrocannabinol (THC). Synthetic cannabinoids (SCs) can signal via the classical endogenous cannabinoid system (ECS) and the greater endocannabidiome network, highlighting their signalling complexity and far-reaching effects. Dronabinol and nabilone, which mimic THC signalling, have been approved by the Food and Drug Administration (FDA) for treating nausea associated with cancer chemotherapy and/or acquired immunodeficiency syndrome (AIDS). However, there is ongoing interest in these two drugs as potential analgesics for a variety of other clinical conditions, including neuropathic pain, spasticity-related pain, and nociplastic pain syndromes including fibromyalgia, osteoarthritis, and postoperative pain, among others. In this review, we highlight the signalling mechanisms of FDA-approved synthetic cannabinoids, discuss key clinical trials that investigate their analgesic potential, and illustrate challenges faced when bringing synthetic cannabinoids to the clinic.
Chapter
Full-text available
Introduction: This work is aimed at understanding the endocannabinoid system and its derivatives, showing in a timeline where we find ourselves in relation to a controversial and marginalized subject. Methodology: The text presents a narrative review of the literature, supported by studies from the PubMed and SciELO platforms. Results and Discussion: In the face of chronic inflammatory processes, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) have been shown to be a therapeutic option in the control of nociception in some diseases, with the potential to relieve pain through activated CB1 and CB2 cannabinoid receptors, which in turn modulate responses to nociceptive stimuli, in particular, induce peripheral tissue repair. Conclusion: With more than 4,500 years of therapeutic use, today, the lack of standardization of drugs and the lack of evidence for future therapeutic solidification does not completely discredit its current role, understanding that more benefits than risks are presented.
Article
» Cannabinoids, such as D9-tetrahydrocannabinol and cannabidiol, interact with endocannabinoid receptors in the central nervous system and immune system, potentially offering pain relief. The entourage effect, resulting from the interaction of multiple cannabis components, may enhance therapeutic impact and efficacy, making them promising candidates for exploring pain relief in spine operations, known to be among the most painful operative procedures. » The use of cannabinoids in pain management requires careful consideration of safety, including their cognitive and psychomotor effects, potential cardiovascular risks, risk of dependence, mental health implications, and drug interactions. » Few studies have analyzed cannabinoid use in relation to spine surgery, with variable results reported, indicating possible effects on reoperation rates, mortality, complications, postoperative opioid use, and length of hospital stay. » Current knowledge gaps exist in the understanding of cannabinoid effects on spine surgery, including the exploration of different administration routes, timing, dosage, and specific outcomes. In addition, mechanistic explanations for the observed results are lacking. » Ethical considerations related to informed consent, medical expertise, societal impact, and legal compliance must also be thoroughly addressed when considering the utilization of cannabinoids in spinal pathologies and back pain treatment.
Article
Objectives Placement of percutaneous spinal cord stimulator (SCS) implant has become a therapeutic option for various chronic pain conditions; however, early surgical explant still occurs. Unfortunately, evidence regarding the incidence of early surgical explant, and patient-specific factors and comorbidities associated with such, is limited and mixed. The objective of this retrospective analysis was to elucidate the incidence and predictors of percutaneous SCS explant within the first two years of device placement. Materials and Methods The PearlDiver-Mariner Patient Record Database of all payer claims was used to identify patients who underwent percutaneous lead SCS implant (leads and generator) with subsequent explant within two years of initial device implant. The primary outcome was to determine the incidence of SCS explant within the first two years of device placement. Secondary outcomes included evaluating the effects of several patient-specific comorbidities on explant rates using univariate regression analysis. Results Across the database, a total of 52,070 patients who underwent percutaneous lead SCS implant were included, of whom 3104 (5.96%) had SCS explant within the first two years. Most explants occurred within the first-year time interval at 72.8% (2260 patients), whereas only 27.2% (844 patients) had SCS explant between years one and two. At the one-year time interval, covariates associated with an increased odds ratio (OR) (95% CI) of SCS explant were 1) depression (1.39 [1.26, 1.52]), 2) chronic preoperative (1.27 [1.16, 1.39]) or postoperative (1.23 [1,13, 1.36]) opioid use, 3) cannabis abuse (1.58 [1.20, 2.02]), 4) tobacco use (1.13 [1.04, 1.23]), and 5) coagulopathy (1.22 [1.07, 1.38]). In contrast, the OR of explant was lower in patients who were older, men, or had diabetes (complicated or uncomplicated). All associated covariates became nonsignificant after the first year of SCS implant (ie, between the first and second years), and only depression and tobacco use remained as associated factors for device explant. Conclusions Our retrospective analysis highlights that the rate of percutaneous SCS explant appears to considerably decrease after the first year of device implant. Furthermore, this analysis sheds additional insights into patients who may be at risk of early percutaneous SCS explant, especially within the first year of device placement, and underscores the importance of a continued multidimensional/biopsychologic assessment in patients with chronic pain.
Article
Full-text available
Purpose of review: The current review aims to summarize the state of research on cannabis and sleep up to 2014 and to review in detail the literature on cannabis and specific sleep disorders from 2014 to the time of publication. Recent findings: Preliminary research into cannabis and insomnia suggests that cannabidiol (CBD) may have therapeutic potential for the treatment of insomnia. Delta-9 tetrahydrocannabinol (THC) may decrease sleep latency but could impair sleep quality long-term. Novel studies investigating cannabinoids and obstructive sleep apnea suggest that synthetic cannabinoids such as nabilone and dronabinol may have short-term benefit for sleep apnea due to their modulatory effects on serotonin-mediated apneas. CBD may hold promise for REM sleep behavior disorder and excessive daytime sleepiness, while nabilone may reduce nightmares associated with PTSD and may improve sleep among patients with chronic pain. Research on cannabis and sleep is in its infancy and has yielded mixed results. Additional controlled and longitudinal research is critical to advance our understanding of research and clinical implications.
Article
Full-text available
The treatment of failed back surgery syndrome (FBSS) can be equally challenging to surgeons, pain specialists, and primary care providers alike. The onset of FBSS occurs when surgery fails to treat the patient’s lumbar spinal pain. Minimizing the likelihood of FBSS is dependent on determining a clear etiology of the patient’s pain, recognizing those who are at high risk, and exhausting conservative measures before deciding to go into a revision surgery. The workup of FBSS includes a thorough history and physical examination, diagnostic imaging, and procedures. After determining the cause of FBSS, a multidisciplinary approach is preferred. This includes pharmacologic management of pain, physical therapy, and behavioral modification and may include therapeutic procedures such as injections, radiofrequency ablation, lysis of adhesions, spinal cord stimulation, and even reoperations.
Article
Full-text available
The research of new therapeutic strategies for neuropathic pain represents a major current priority. Important drawbacks to advance in the development of these therapies are the limited translational value of the animal models now available and the elucidation of the complex neuronal and immune pathophysiological mechanisms underlying neuropathic pain. One of the neurotransmitter systems participating in neuropathic pain control that has recently raised a particular interest is the endocannabinoid system. This system is highly expressed in neurons and immune cells, and plays a crucial role in the development of neuropathic pain. Preclinical studies have provided important findings revealing the potential interest of the endocannabinoid system for neuropathic pain treatment. These studies have reported the analgesic effects of cannabinoid agonists in multiple neuropathic pain models and have identified specific targets within this system to develop more effective and safe analgesic compounds. However, further studies using more relevant neuropathic pain animal models are required to confirm these interesting results. Several clinical studies suggest that cannabinoids significantly reduced neuropathic pain, although most of these trials fail the required standards of quality. The different pain patient populations include in the systematic reviews also make difficult to get adequate conclusions. Therefore, additional clinical trials that consider an adequate number of patients, use active treatments as controls and longer duration of administration are required to have an adequate profile of the effectiveness and safety of cannabinoids in neuropathic pain.
Article
Full-text available
An updated systematic review of randomized controlled trials examining cannabinoids in the treatment of chronic non-cancer pain was conducted according to PRISMA guidelines for systematic reviews reporting on health care outcomes. Eleven trials published since our last review met inclusion criteria. The quality of the trials was excellent. Seven of the trials demonstrated a significant analgesic effect. Several trials also demonstrated improvement in secondary outcomes (e.g., sleep, muscle stiffness and spasticity). Adverse effects most frequently reported such as fatigue and dizziness were mild to moderate in severity and generally well tolerated. This review adds further support that currently available cannabinoids are safe, modestly effective analgesics that provide a reasonable therapeutic option in the management of chronic non-cancer pain.
Article
Full-text available
Failed back surgery syndrome is an unhelpful term that hides the true issues concerning the mechanism of pain and subsequent therapies that patients with chronic radicular neuropathic pain are exposed to. Patients with chronic radicular neuropathic pain who have had previous spinal surgery are numerous and comparable in prevalence and incidence to other pain associated diseases such as rheumatoid arthritis but with higher annual costs. Better recognition of this patient group with the effective recognition and multi-disciplinary care aimed at achieving best patient and societal outcomes is required.
Article
Background: Cannabidiol (CBD) is among the major secondary metabolites of Cannabis devoid of the delta-9-tetra-hydrocannabinol psychoactive effects. It is a resorcinol-based compound with a broad spectrum of potential therapeutic properties, including neuroprotective effects in numerous pathological conditions. CBD neuroprotection is due to its antioxidant and antiinflammatory activi-ties and the modulation of a large number of brain biological targets (receptors, channels) involved in the development and maintenance of neurodegenerative diseases. Objective: Aim of the present review was to describe the state of art about the pre-clinical research, the potential use and, when existing, the clinical evidence related to CBD in the neurological field. Method: Collection of all the pre-clinical and clinical findings carried out investigating the effects of CBD alone, not in combination with other substances, in the neurological arena with the exclu-sion of studies on neuropsychiatric disorders. Results: Laboratory and clinical studies on the potential role of CBD in Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), Huntington's disease (HD), amyotrophic lateral sclerosis ALS), cerebral ischemia, were examined. Conclusions: Pre-clinical evidence largely shows that CBD can produce beneficial effects in AD, PD and MS patients, but its employment for these disorders needs further confirmation from well designed clinical studies. CBD pre-clinical demonstration of antiepileptic activity is supported by recent clinical studies in human epileptic subjects resistant to standard antiepileptic drugs showing its potential use in children and young adults affected by refractory epilepsy. Evidence for use of CBD in PD is still not supported by sufficient data whereas only a few studies including a small number of patients are available.
Article
Introduction: The US Federal Drug Administration (FDA) approved 3 medications for treating fibromyalgia syndrome (FMS). There have been no additional FDA approvals since January 2009 and the efficacy of the FDA-approved medications for FMS has been questioned. Areas covered: The "search for studies" tool using clinicaltrials.gov and PubMed were employed. The term, "fibromyalgia" was used for clinicaltrials.gov. The terms employed for PubMed were "Name-of-Drug Fibromyalgia", "Fibromyalgia Treatment" or "Fibromyalgia Drug Treatment." Clinical trials were reviewed if they were prospective and blinded, and if they employed a comparator, either placebo or another pharmaceutical. Expert Commentary: Progress toward standardizing the outcome measures for FMS clinical trials have been made but challenges remain. Several pharmaceutical candidates for FMS have been tested since 2009. The results of these studies with potential novel targets for drug development for FMS were reviewed including the results of trials with sodium oxybate, quetiapine, esreboxetine,nabilone, memantine, naltrexone, and melatonin.
Article
Neuropathic pain (NP) is a significant medical and socioeconomic burden. Epidemiological surveys have indicated that many patients with NP do not receive appropriate treatment for their pain. A number of pharmacological agents have been found to be effective in NP on the basis of randomized controlled trials including, in particular, tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitor antidepressants, pregabalin, gabapentin, opioids, lidocaine patches, and capsaicin high-concentration patches. Evidence-based recommendations for the pharmacotherapy of NP have recently been updated. However, meta-analyses indicate that only a minority of patients with NP have an adequate response to drug therapy. Several reasons may account for these findings, including a modest efficacy of the active drugs, a high placebo response, the heterogeneity of diagnostic criteria for NP, and an inadequate classification of patients in clinical trials. Improving the current way of conducting clinical trials in NP could contribute to reduce therapeutic failures and may have an impact on future therapeutic algorithms.