To elaborate recommendations regarding neuropathic pain management in spinal cord injury patients. The goal was to evaluate the efficacy of local anesthetic therapeutics including intrathecal or epidural treatments, sympathetic and nerve blocks.
The methodology, proposed by the French Society of Physical Medicine and Rehabilitation (SOFMER), includes a systematic revue of the literature, the gathering of information regarding current clinical practice and a validation by a multidisciplinary panel of experts.
The results of the literature review do not validate the efficacy of clonidine, baclofen, morphine or lidocaine administered via intrathecal (IT) drug delivery or epidural injections on neuropathic pain in spinal cord injury patients. One reason could be the methodological limitations of the studies. Another reason could be that in most cases the evaluation is done after one single dose injection, thus preventing the authors from assessing the efficacy of the treatments on the long-term. Various clinical practices experiences lead us into thinking that there is, in some cases, a real efficacy for IT baclofen delivery, but this still remains to be properly defined in terms of patients characteristics and type of neuropathic pain. Regarding anesthetic nerve root blocks and sympathetic blocs, no element is available to validate the efficacy of these techniques.
There is not a sufficient level of proof to recommend using IT or epidural drug delivery for treating neuropathic pain. However, according to the clinical practices data reviewed, we can suggest to conduct further studies on the impact of IT baclofen delivery that seems to have a pain-relieving impact in some situations. It would be interesting to identify the subgroups of patients that could benefit from this treatment.
Élaborer des recommandations concernant la prise en charge de la douleur neuropathique chez des patients blessés médullaires (BM). Il s’agit d’évaluer l’efficacité des thérapeutiques locorégionales incluant les thérapeutiques intrathécales et épidurales, les blocs anesthésiques et sympathiques.
Matériel et méthode
La méthodologie utilisée, proposée par la Société française de médecine physique et de réadaptation (Sofmer), associe une revue systématique de la littérature, un recueil des pratiques professionnelles, une validation par un panel pluridisciplinaire d’experts.
Les résultats de la revue de la littérature ne permettent pas démontrer une efficacité de la clonidine, de la morphine, la lidocaïne ou du baclofène infusé par voie intrathécale (IT) ou épidurale sur la douleur neuropathique. Cela est lié, d’une part, aux insuffisances méthodologiques des études, d’autre part, au fait que l’évaluation est réalisée dans la majorité des cas après administration de doses uniques, ce qui ne permet de conclure quant à l’efficacité d’une administration au long cours. Le recueil des pratiques professionnelles permet de penser qu’il existe dans certains cas une efficacité du baclofène IT mais reste à définir dans quels groupes de patients et sur quelles modalités de la douleur neuropathique. En ce qui concerne les blocs anesthésiques et sympathiques, aucun élément ne semble montrer une quelconque efficacité de ces techniques.
Il n’existe pas de niveaux de preuve suffisants pour recommander l’utilisation de certaines substances par voie IT ou épidurale pour traiter les douleurs neuropathiques. Compte tenu du recueil des pratiques professionnelles, nous pouvons cependant suggérer la réalisation d’études évaluant l’effet du baclofène IT qui semble être efficace dans certaines situations. Il serait intéressant d’identifier les groupes de patients pouvant bénéficier de ce traitement.
Many therapeutic approaches aim to relieve the chronic pain in spinal cord injury (SCI) patients. There are pharmacological treatments available. Among them, the various delivery methods are: general drug delivery (oral, intravenously, transdermally), but also local delivery (IT, anesthetic nerve root blocks or sympathetic blocks). The goal of this work is to do a review of the literature to select the studies evaluating the impact of pharmacological treatments delivered locally for relieving the neuropathic pain in SCI patients ( Table 1 ).
|Author||Drug (s)||Type of study according to the ANAES classification||Number of patients||Delivery method||Results||Dose||Grade|
|Siddall et al.||Morphine Clonidine||Low power comparative study Level 2||15||IT||No effect with the 2 drugs delivered separately. Efficacy in 3/15 when combined||Single Dose||B|
|Glynn et al.||Morphine Clonidine Buprenorphine||Comparative study with major biases Level 4||15||E||Effect + clonidine = 10/15 Effect + morphine = 5/15 Effect + buprenorphine = 2/5||Single Dose||C|
|Glynn et al.||Clonidine||Case series Level 4||6||E||Pain decrease in 4/6 patients||Single Dose||C|
|Loubser and Donovan||Lidocaine||Low power comparative study Level 2||21||IT||13/21 mean pain improvement of 37.8% for 2 h 4/21 with placebo||Single Dose||B|
|Loubser and Akman||Baclofen||Case series Level 4||9||IT||No pain-relieving impact||Chronic delivery||C|
Material and method
The method used, developed by the French Society of Physical Medicine and Rehabilitation (SOFMER) , includes three steps: a systematic review of the literature, a compilation of current clinical practices and a validation by a multidisciplinary panel of experts.
Systematic review of the literature and studies selection
The keywords used by the scientific committee for this question were in the English language: chronic neuropathic pain in SCI, human, adult and regional anesthetic interventions, sympathetic blocks, nerve blocks, intrathecal administration, intrathecal baclofen, intrathecal morphine, intrathecal clonidine, and pumps. The keywords in the French language were: douleur chronique chez le blessé médullaire traumatique, humain, adulte et bloc anesthésique régional, bloc nerveux périphérique, bloc sympathique, traitement intrathécal, baclofène IT, clonidine IT, morphine IT, pompes .
Data analysis was performed independently using the double-reading mode, two readers from two different medical specialties, one anesthesiologist and one Physical Medicine and Rehabilitation (PM&R) physician. They met afterwards to put together their results and draw a synthesis of their work.
Literature review and selected articles
The scientific committee selected 65 articles
The analysis of these different works and after reading all the 65 articles led to a selection of only five articles that met our selected criteria. No article was added to the selection. Two articles only belonged to the level 2 ANAES classification (National French Health Authority). All the other articles kept were grade 4 studies. All studies that included other populations besides SCI patients were excluded when the treatment impact on SCI patients could not be analyzed separately.
Results from the articles analysis
Intrathecal or epidural drug delivery
The first study is a randomized, double-blind study inluding 15 patients comparing the effect of placebo, morphine, clonidine or a combination of these two drugs after one single IT injection. The two drugs injected separately had no significant impact. Their impact was even less than that of the placebo. A 50% pain decrease was reported for three patients out of 15 patients after a concomitant injection of both drugs but a similar effect was reported for the placebo injection. In fact, 30% of patients described at least a 50% pain improvement with the placebo injection. It is a low power comparative study (Level 2).
The second study is a non-randomized, single-blind study evaluating the effect of morphine (5 mg) and/or clonidine (150 μg) delivered by epidural injection in 15 SCI patients . Patients whose pain was not decreased by morphine or clonidine received afterwards a buprenorphine injection. The epidural injections were all single doses of each of these drugs. The pain decrease was not quantified. Morphine led to a pain decrease in five patients out of which three also reported a pain decrease after a clonidine epidural injection. Among the 10 patients, who did not report any pain improvement with morphine, seven described a pain decrease with clonidine. Two patients reported a pain decreased with buprenorphine. One patient reported no improvement at all with any of these drugs. It is a level 4 study according to the ANAES recommendations.
Glynn et al. in another study evaluated the impact of a single 150 μg dose of clonidine delivered via an epidural injection in six patients. Three patients out of six described a pain decrease above or equal to 50%. We should note however that the type of pain improved was not specified. The patients reporting a pain improvement also described simultaneously a spectacular improvement of their muscle spasms. It is possible that the pain improvement acted on the musculoskeletal component instead of the neuropathic one. The study’s main goal was to evaluate the pharmacokinetics action of epidural clonidine. The pain-relieving effect was only a secondary objective for this study. It is level 4 study according to the ANAES recommendations. A study evaluated the effect of a single-dose IT lidocaine delivery . It is a double-blind versus placebo study that included 21 patients (level 2 ANAES). Nine patients described at least a 50% pain decrease with the IT lidocaine for a mean duration of 2 hours. Three patients described at least a 50% pain decrease with the placebo.
The last study (case study) evaluated the effect of IT baclofen in nine SCI patients for their chronic pain . Seven patients reported no improvement on their chronic pain, two had more pain at six and 9 months post-implantation of the intrathecal pump.
Anesthetic nerve root blocks
No study evaluated the effect of anesthetic nerve root block on the neuropathic pain of SCI patients.
We did not find any study that evaluated the effect of sympathetic blocks on the neuropathic pain of SCI patients.
Data collection of clinical practices experiences
Three multiple-choice questions were asked to the SOFMER attendees and via the SOFMER website (Appendix 1). One hundred and sixteen physicians attended the conference and answered the questionnaire as well as 50 more via the website. The first question unveiled that half of the physicians used none of the drugs studied in the literature in their daily clinical practice. IT baclofen is used by a little more than one quarter of the physician for neuropathic pain management in SCI patients. The other drugs (morphine and clonidine) are used by around 10% of practitioners. Twenty percent of the practitioners use also a combination of drugs for treating neuropathic pain. The second question showed that two-thirds of them showed an improvement on the neuropathic pain in some case with IT baclofen to treat debilitating spasticity in SCI patients.
The third question shows that very few physicians use selective nerve root blocks or sympathetic blocks for treating neuropathic pain in SCI patients since only 15% of them declare using these techniques sometimes for neuropathic pain management.
We are surprised by the very low number of studies that evaluated the effect of local injections for treating the neuropathic pain of SCI patients.
Out of the five studies selected, only two had a methodological quality that was satisfying (level 2 on the ANAES grid). The other studies were qualified with a level 4. Pain was not systematically quantified in all these studies . It was also only qualitatively assessed in one single study that differentiated in its evaluation neuropathic and musculoskeletal pain. The other studies evaluated the pain changes in a global manner without focusing on the pain type or characteristics. It seems difficult in this context, due to the lack of defined pain type or characteristics, to know precisely on which pain component the drug acted. Finally, no study evaluated the impact of these drugs on the various neuropathic pain components (segmental pain at the level of injury and below-level neuropathic pain).
Another one of these studies limitations is linked to the drug delivery itself. In four studies out of five only single doses were delivered. Only the Loubser study evaluated a chronic IT baclofen delivery. In fact, this study did not validate the efficacy of baclofen on neuropathic pain. The other studies all evaluated the effect of single doses, which makes it impossible to position ourselves regarding the efficacy of chronic delivery. This is even more important when we know that for some types of drugs such as clonidine, a quick-setting tolerance was demonstrated in protocols that evaluated its effect on the bladder/sphincter functions and spasticity .
Additional studies assessing the effect of chronic delivery of these drugs would be necessary to validate their long-term efficacy.
Regarding anesthetic nerve root blocks and sympathetic blocks, we could not find any study that evaluated these techniques. The results to the question asked to the SOFMER attendees confirm the weak relevance of these techniques in our daily practice.
Contrarily to the literature results regarding IT baclofen, 50% of practitioners seem to observe in their daily practice an improvement of neuropathic pain with this treatment. It is also used by one-quarter of physicians to try and manage the neuropathic pain of their SCI patients. It would be relevant to conduct further studies on what type of neuropathic pain and for which type of injury (complete, incomplete) this treatment can be beneficial to SCI patients.
Finally, confirming the very disappointing results found in the literature regarding the IT drug delivery to treat neuropathic pain, half of the practitioners never use this delivery method for their patients.
Conclusion and recommendations
The low level of proof of the studies found in the literature does not allow for recommending the use of drugs such as clonidine, morphine, lidocaine or baclofen in daily practice to treat the neuropathic pain of SCI patients. The recommendation grades are B or C, meaning the scientific presumption (two studies) or the low level of proof (three studies). However, the data collection on clinical practices unveils a potential positive impact of IT baclofen for neuropathic pain management in some patients. Conducting further studies with a rigorous methodology on assessing the effect of this drug on the long-term could help validate the relevance of this treatment. The other questions that remain to be answered are those regarding the neuropathic pain characteristics and the level of injury of patients that could benefit from this treatment.
In light of the results of this literature review and the data collection regarding clinical practices, it seems difficult to recommend the use of anesthetic nerve root and sympathetic blocks to treat neuropathic pain in SCI patients.
Appendix 1. Answers to the question asked to the 116 physicians attending the SOFMER conference and the 50 others that answered on the SOFMER website.
Do you use one or more of the following drug by intrathecal delivery to treat neuropathic pain in SCI patients? (multiple answers are possible).
Combination of these two drugs: 21.18%.
Did you observe an efficacy of IT baclofen on neuropathic pain in SCI patients with an intrathecal pump to treat their spasticity?
Do you use anesthetic nerve root blocks or sympathetic blocks to treat neuropathic pain in SCI patients?
dnk: does not know