Curr Pain Headache Rep (2014) 18:452 DOI 10.1007/s11916-014-0452-1
NEUROPATHIC PAIN (E EISENBERG, SECTION EDITOR)
Conservative Treatments for Lumbar Radicular Pain Gregory Fleury & Michael J. Nissen & Stéphane Genevay
Published online: 18 September 2014 # Springer Science+Business Media New York 2014
Abstract Lumbar radicular pain is a frequent medical pathology and represents a significant burden on society. The diagnosis of sciatica is largely clinical, in the setting of a combination of radicular pain and neurologic deficits (motor, reflexes, and/or sensation) or a positive straight leg raise test. Imaging is generally not necessary for sciatica, except in the presence of warning signs or in the setting of persisting or worsening pain. The recommended first-line treatment has not yet been clearly established. The choice of a conservative treatment approach combined with simple analgesics in the initial stages seems to be reasonable. A detailed discussion with the patient is important to explain the fact that surgery may only be necessary in the event of pain persisting in excess of 3 months or because of the development or worsening of a neurologic deficit. More high quality studies are clearly required to assist the medical practitioner in knowing how best to treat this group of patients. Keywords Sciatica . Radicular leg pain . Radiculopathy . Herniated disc . Treatment . Pharmacotherapy
Introduction Lumbar radicular pain is generally referred to as sciatica. Although it is a widespread condition, the scientific literature is rather confusing, mainly because of the fact that it is a syndrome encompassing clinical symptoms and signs rather than a specific pathologic entity. In addition, in the absence of a widely accepted consensus definition [1], for decades This article is part of the Topical Collection on Neuropathic Pain G. Fleury : M. J. Nissen : S. Genevay (*) Division of Rheumatology, University Hospitals of Geneva, 26 Avenue de Beau-Séjour, 1211 Geneva 14, Switzerland e-mail: [email protected]
studies and systemic reviews failed to differentiate these patients from those with nonspecific low back pain [2–4]. There is, however, a need for better recognition of this condition, as it consumes a considerable proportion of health resources and is a major cost to society, particularly with regards to absenteeism [5]. Selim et al. [6] reported that patients with radicular symptoms have more pain than those with isolated low back pain and that they have a greater tendency to chronicity [7]. The management of this pathology is therefore a significant challenge for both general practitioners and specialists. It is generally accepted that treatment should be conservative for at least the first 2–3 months. Progressive significant motor weakness or the cauda equina syndrome are exceptions to this rule as most would advocate immediate surgical management. However, there are very few randomized studies comparing the different treatment strategies of the various clinical presentations of sciatica. This article aims to review the nonsurgical treatments for sciatica with particular focus on the commonly used pharmacologic treatments, as well as potential emerging therapies. According to a recent systematic review, sciatica has a prevalence of between 1.2 % and 43 % in the general population [8]. This broad range of prevalence highlights the lack of consensus toward a universally accepted definition! However, when diagnosis relies on physical examination, a prevalence of 4.8 % is reported [8]. The annual incidence is about 0.5 % in adults [9•]. Sciatica is commonly characterized by unilateral lower limb radicular pain (ie, pain radiating in a specific dermatome) and is often associated with neurologic symptoms such as numbness, loss of sensitivity, diminished reflexes, and motor weakness. Although several different etiologies may result in sciatica (Table 1), more than 90 % are related to lumbar disc herniation (DH) [11], which is defined as a localized displacement of disc material (nucleus pulpous and/or annulus fibrosis) beyond the normal margins of the intervertebral disc space [12••]. In the absence of widely
452, Page 2 of 5
Curr Pain Headache Rep (2014) 18:452
Table 1 Differential diagnosis of radicular pain not related to disc herniation Malignancy Infection Vascular compression Muscular compression Bony compression Epidural Gynecologic Metabolic
Metastatic, sarcoma, neuroma, hemangioblastoma Abscess, discitis, epiduritis Epidural thrombosis, abnormal pelvic venous plexus, gluteal artery pseudo-aneurysm Piriformis syndrome Degenerative spinal stenosis, foraminal stenosis, osteophytes of the sacroiliac joint Epidural lipomatosis, epidural adhesions (eg postoperative) Pelvic endometriosis, uterine fibroid Diabetic painful amyotrophy, alcoholic neuropathy
Adapted from: Stafford MA, Peng P, Hill DA. Sciatica: a review of history, epidemiology, pathogenesis, and the role of epidural steroid injection in management. Br J Anaesth. 2007;99:461–73 [10]
accepted classification criteria, we would advocate the use of the eligibility criteria used in the SPORT’s trial [13]: radicular pain associated with either a clinical sign of nerve root irritation, the straight leg raising (SLR) test (for the L5 or S1 nerve roots) or the reverse SLR (for the L3 or L4 nerve roots), or a neurologic deficit, either sensitive, reflex or motor strength, associated with a herniated disc at the level and side corresponding to the radicular pain. Of note, the SLR test has a sensitivity of 92 % and a specificity of 28 % whereas the crossed SLR test showed a high specificity (90 %) but with low sensitivity (28 %) [14]. No figures have been reported for the reverse SLR. Although the exact pathophysiology remains unclear, there is certainly an element attributable to local mechanical effects of direct contact of the herniated disc with the nerve root, as well as an inflammatory component with potential activation of the immune system [15•]. Of note, compression is not an absolute requirement and the size of the herniated disc doesn’t influence the clinical presentation [15•]. Risk factors have not clearly been identified, although obesity, heavy manual work, and smoking have all been proposed [16]. In a recent study, the use of tobacco was the only risk factor found to be associated with an elevated risk of hospitalization for sciatica [17].
back. The fear of movement or kinesiophobia is a factor that has been linked to a less favorable outcome [18] and needs to be addressed. The causes of sciatica and the natural course of the disease should also be discussed at an early stage [11]. Imaging is not necessary initially, unless there are symptoms of other potentially serious diseases (ie, infection or tumor) or if the symptoms worsen or persist. This is an important point to discuss with the patient who will often expect an MRI to be performed at the first presentation. Based on well conducted randomized control trials (RCT) [19, 20], several systematic reviews [2, 11, 21] found no evidence for a role of bed rest in sciatica. However, in contrast to acute low back pain, no deleterious effects have been reported [2]. Nevertheless, in contrast with low back pain, there is no evidence that physical activity is beneficial for these patients [22]. Amongst the different physiotherapy techniques advocated, traction has been suggested by many, but a systematic review failed to confirm a positive effect of either intermittent or continuous traction compared with placebo in terms of pain relief and returning to work [23, 24]. In a single RCT, transcutaneous electrical nerve stimulation (TENS), often used for neuropathic pain, showed some efficacy with a reduction of the radicular component of pain [25]. In a systematic review published in 2007, Luijsterburg et al. reported that active exercises provided by physiotherapists were not more effective than usual care [26]. Since this review, to the best of our knowledge, only 2 RCT have been published on the effect of physiotherapy in sciatica. In the first study, the addition of exercises provided under the guidance of a physiotherapist in addition to the general practitioner’s care, provided a better improvement in terms of “patient perceived global effect” compared with general practitioner’s care alone [27]. The second study demonstrated that symptom-guided exercises (also known as “McKenzie” method) produced a slightly better outcome when compared with sham exercises [28]. Manipulations in the context of a herniated disc have been controversial. Recently, in a randomized trial, McMorland et al. reported that chiropractic spinal manipulation was as effective as microdiscectomy at 1-year follow-up [29]. However, more than a third of the patients in the manipulation group crossed over to the surgery arm with a subsequent significant improvement. Nociceptive Pain Treatments
Treatments Nonpharmacologic Treatments The first step is an interactive discussion between the therapist and the patient, which will establish the foundation for successful therapy. It is critical to listen to the concerns and fears of the patient at an early stage, in order to address their concerns that the sciatica could represent a broken or weak
In the acute phase, sciatic pain is considered to be a predominantly nociceptive pain [23] and is currently being treated in a similar way to low back pain [15•], with adaptation of the intensity of the treatment according to the intensity of pain and following the 3 steps of the WHO recommendations [30]. However, there is a paucity of good quality studies to support this approach. There are no studies evaluating the efficacy of acetaminophen in sciatica. Mixed results have been found for
Curr Pain Headache Rep (2014) 18:452
NSAIDs and Pinto et al. in their systematic review concluded that there was limited support for the use of NSAIDs to relieve pain in the short term with no study demonstrating the superiority of one molecule over another [31]. As for opioid analgesics, no study has been published concerning the use of tramadol. One randomized controlled trial in chronic sciatica found no effect of morphine alone or in combination with nortriptyline [32]. More recently, in a post hoc analysis of the SPORT trial with inclusion of more than 1000 patients, Radcliff et al. [33•] found that the use of opioids (prescribed in slightly more than half the patients) was associated with worse baseline pain and quality of life. More interestingly, they observed an increased crossover to surgical treatment, whereas a decrease would have been expected in the case of significant efficacy. In a RCT conducted in hospitalized patients, the well-known benzodiazepine diazepam, often prescribed for muscle relaxation showed no effect, and conversely was associated with a prolongation of hospital stay because of side effects [34]. Neuropathic Pain Treatment When sciatic pain becomes chronic, a neuropathic component is frequently reported [35•] and neuropathic pain treatments could be considered. Antidepressants have been advocated for the treatment of back pain in chronic sciatica [36], however, neither topiramate [37] or nortriptyline [32] have demonstrated efficacy in chronic sciatic pain. Intriguingly, a large beneficial effect was reported in a RCT using gabapentin (900 to 3600 mg/d) [38], whereas no effect was observed in a more recent RCT with pregabalin [39], albeit using a nonconventional design. This surprising lack of efficacy might be due to the difficulty of the clinician in selecting appropriate patients [40]. Corticosteroids Corticosteroids have been used for sciatica for many decades and by various routes of administration (oral, IM, and IV) although their role remains subject to controversy. In a systematic review, Roncoroni et al. in 2011 [9•] reported that the systemic use of steroids was not superior to placebo in preventing work absenteeism and did not reduce the requirement for analgesics, but conversely resulted in an important increase in side effects (number needed to harm: 20), including an increased risk for surgery. More recently, Pinto et al. confirmed the lack of efficacy of oral steroids in sciatica but concluded a small beneficial effect of steroids in the short term when used intravenously [31]. This result referred mainly to the study published by Finckh et al. [41] who reported a transitory effect of only 48 hours of benefit in terms of leg pain following IV injection of 500 mg of solumedrol. Finally, the American Pain Society does not recommend the use of
Page 3 of 5, 452
steroids for sciatica because of a lack of evidence for their efficacy [42]. Turning now to the subject of corticosteroid injections within and adjacent to the spinal canal. Transforaminal injection is the most effective route of administration of corticosteroid into the spinal canal [15•] and it is the one recommended by the North American Spine Society for its short-term effect, although there is no evidence that it decreases the requirement for surgery [12••]. Following several case reports of paraplegia because of spinal cord infarction after transforaminal injection [43–46], the French National Health Security Agency has published a warning stating that alternative methods of injection should be preferred (translaminar or caudal), particularly in patients with prior spinal surgery [47]. Of note, digital subtraction angiography and use of an anesthetic test dose did not prevent these catastrophic events [48]. In summary, we advocate the use of spinal injection initially via a caudal or translaminar route, reserving use of the transforaminal approach for cases resistant to other routes of administration and after patients have been fully informed about the potential risks. Very recently, the results of a network meta-analysis for the treatment of sciatica, were published [49••]. This statistical method allows the simultaneous comparison of all treatment strategies and indirect comparisons of these treatments. The findings supported the effectiveness of nonopioid medications and epidural injection along with disc surgery whereas bed rest, education/advice (when used alone), NSAIDs, exercise therapy, traction and percutaneous discectomy were not supported by the evidence. Experimental Pharmacologic Treatments In recent years, new pharmacologic agents have been investigated. As TNF-alpha appeared to be a key molecule in animal models of sciatica [15•] and was found at increased levels around the nerve roots of patients suffering from sciatica [50], TNF inhibitors have been the most widely studied of the various biological agents. Several randomized studies using epidural injection of etanercept, a fusion protein containing a TNF-alpha receptor, have been published. A meta-analysis found low evidence that epidural etanercept has a low-tomoderate effect size [51]. A unique RCT with subcutaneous injection of adalimumab, a monoclonal antibody against TNFalpha, found a small benefit in terms of pain, as well as a decreased need for surgery at 6 months [52] that was confirmed at 3 years follow-up [53]. A second meta-analysis concluded that there was currently insufficient evidence to recommend the use of TNF-alpha inhibitors for sciatica, but sufficient evidence to suggest that larger RCTs are needed [54••]. The use of Anti-Nerve Growth Factor is another potentially interesting approach to treat sciatica. A recent meta-analysis
452, Page 4 of 5
was conducted encompassing 3 RCTs. A short-term (16 weeks) effect on pain and functional impairment [55] was found, but it was small and not clinically significant. In addition, there was an increased level of side effects in the treated group and more specifically the presence of neurologic side effects such as headache, hyperesthesia, and abnormal peripheral sensation.
Conclusions Radicular pain because of a herniated disc needs to be identified and not confused with mechanical low back pain. Not only is the course of the disease different but, according to available data, treatment effectiveness is also different. Despite the paucity of good quality trials, conservative treatment using analgesics, neuropathic pain treatments, and epidural corticosteroids remain the core of management. Surgery should be proposed when disabling pain persists despite 3 months of standard care or in the setting of major neurologic complications. Compliance with Ethics Guidelines Conflict of Interest Gregory Fleury and Michael J. Nissen declare that that have no conflict of interest. Stéphane Genevay has received an unrestricted scientific grant from Abbott. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.
References Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance 1.
2.
3.
4.
Genevay S, Atlas SJ, Katz JN. Variation in eligibility criteria from studies of radiculopathy due to a herniated disc and of neurogenic claudication due to lumbar spinal stenosis: a structured literature review. Spine. 2010;35:803–11. Hagen KB, Jamtvedt G, Hilde G, Winnem MF. The updated Cochrane review of bed rest for low back pain and sciatica. Spine. 2005;30:542–6. Goh L, Bawendi A, Samanta J, Samanta A. An evidence-based approach to the management of low back pain and sciatica: how the evidence is applied in clinical cases. Musculoskelet Care. 2003;1: 119–30. Airaksinen O, Brox JI, Cedraschi C, Hildebrandt J, Klaber-Moffett J, Kovacs F, et al. Chapter 4. European guidelines for the management of chronic nonspecific low back pain. Eur Spine J. 2006;15 Suppl 2:S192–300.
Curr Pain Headache Rep (2014) 18:452 5.
Awad JN, Moskovich R. Lumbar disc herniations: surgical vs nonsurgical treatment. Clin Orthop Relat Res. 2006;443:183–97. 6. Selim AJ, Ren XS, Fincke G, Deyo RA, Rogers W, Miller D, et al. The importance of radiating leg pain in assessing health outcomes among patients with low back pain. Results from the Veterans Health Study. Spine. 1998;23:470–4. 7. Chou R, Shekelle P. Will this patient develop persistent disabling low back pain? JAMA. 2010;303:1295–302. 8. Konstantinou K, Dunn KM. Sciatica: review of epidemiological studies and prevalence estimates. Spine. 2008;33:2464–72. 9.• Roncoroni C, Baillet A, Durand M, Gaudin P, Juvin R. Efficacy and tolerance of systemic steroids in sciatica: a systematic review and meta-analysis. Rheumatology. 2011;50:1603–11. Systemic steroids are often prescribed in sciatica as they are easier to deliver than Spine. injections. This study put into question their efficacy and underline the importance of their side effects. 10. Stafford MA, Peng P, Hill DA. Sciatica: a review of history, epidemiology, pathogenesis, and the role of epidural steroid injection in management. Br J Anaesth. 2007;99:461–73. 11. Koes BW, van Tulder MW, Peul WC. Diagnosis and treatment of sciatica. BMJ. 2007;334:1313–7. 12.•• Kreiner DS, Hwang SW, Easa JE, Resnick DK, Baisden JL, Bess S, et al. An evidence-based clinical guideline for the diagnosis and treatment of lumbar disc herniation with radiculopathy. Spine J. 2014;14: 180–91. A useful guideline to help clinicians in the treatment of lumbar radicular pain because of disc herniation. This recent and comprehensive review also underlines the lack of literature on many important questions related to the treatment of this frequent syndrome. 13. Weinstein JN, Tosteson TD, Lurie JD, Tosteson ANA, Hanscom B, Skinner JS, et al. Surgical vs nonoperative treatment for lumbar disk herniation: the Spine Patient Outcomes Research Trial (SPORT): a randomized trial. JAMA. 2006;296:2441–50. 14. Van der Windt DA, Simons E, Riphagen II, Ammendolia C, Verhagen AP, Laslett M, et al. Physical examination for lumbar radiculopathy due to disc herniation in patients with low-back pain. Cochrane Database Syst Rev. 2010. doi:10.1002/14651858.CD007431. 15.• Valat J-P, Genevay S, Marty M, Rozenberg S, Koes B. Sciatica. Best Pract Res Clin Rheumatol. 2010;24:241–52. A comprehensive review on both pathophysiology and treatment for lumbar radicular pain because of disc herniation. 16. Karjalainen U, Paananen M, Okuloff A, Taimela S, Auvinen J, Männikkö M, et al. Role of environmental factors and history of low back pain in sciatica symptoms among Finnish adolescents. Spine. 2013;38:1105–11. 17. Rivinoja AE, Paananen MV, Taimela SP, Solovieva S, Okuloff A, Zitting P, et al. Sports, smoking, and overweight during adolescence as predictors of sciatica in adulthood: a 28-year follow-up study of a birth cohort. Am J Epidemiol. 2011;173:890–7. 18. Haugen AJ, Brox JI, Grøvle L, Keller A, Natvig B, Soldal D, et al. Prognostic factors for non-success in patients with sciatica and disc herniation. BMC Musculoskelet Disord. 2012;13:183. 19. Vroomen PC, de Krom MC, Wilmink JT, Kester AD, Knottnerus JA. Lack of effectiveness of bed rest for sciatica. N Engl J Med. 1999;340:418–23. 20. Hofstee DJ, Gijtenbeek JMM, Hoogland PH, van Houwelingen HC, Kloet A, Lötters F, et al. Westeinde sciatica trial: randomized controlled study of bed rest and physiotherapy for acute sciatica. J Neurosurg. 2002;96:45–9. 21. Luijsterburg PA, Verhagen AP, Ostelo RWJG, van Os AG, Peul WC, Koes BW. Effectiveness of conservative treatments for the lumbosacral radicular syndrome: a systematic review. Eur Spine J. 2007;16:881–99. 22. Dahm KT, Brurberg KG, Jamtvedt G, Hagen KB. Advice to rest in bed vs advice to stay active for acute low-back pain and sciatica. Cochrane Database Syst Rev. 2010. doi:10.1002/14651858. CD007612.
Curr Pain Headache Rep (2014) 18:452 23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.•
34.
35.•
36.
37. 38.
39.
Wegner I, Widyahening IS, van Tulder MW, Blomberg SEI, de Vet HC, Brønfort G, et al. Traction for low-back pain with or without sciatica. Cochrane Database Syst Rev. 2013. doi:10.1002/ 14651858.CD003010 Clarke JA, van Tulder MW, Blomberg SEI, de Vet HCW, van der Heijden GJ, Brønfort G, Bouter LM. Traction for low-back pain with or without sciatica. Cochrane Database Syst Rev. 2007:Issue 2. Art. No.: CD003010. doi:10.1002/14651858.CD003010 Ghoname EA, White PF, Ahmed HE, Hamza MA, Craig WF, Noe CE. Percutaneous electrical nerve stimulation: an alternative to TENS in the management of sciatica. Pain. 1999;83:193–9. Luijsterburg PA, Lamers LM, Verhagen AP, Ostelo RWJG, van den Hoogen HJMM, Peul WC, et al. Cost-effectiveness of physical therapy and general practitioner care for sciatica. Spine. 2007;32: 1942–8. Luijsterburg PA, Verhagen AP, Ostelo RWJG, van den Hoogen HJMM, Peul WC, Avezaat CJJ, et al. Physical therapy plus general practitioners’ care vs general practitioners’ care alone for sciatica: a randomised clinical trial with a 12-month follow-up. Eur Spine J. 2008;17:509–17. Albert HB, Manniche C. The efficacy of systematic active conservative treatment for patients with severe sciatica: a single-blind, randomized, clinical, controlled trial. Spine. 2012;37:531–42. McMorland G, Suter E, Casha S, du Plessis SJ, Hurlbert RJ. Manipulation or microdiskectomy for sciatica? A prospective randomized clinical study. National University of Health Sciences. J Manipulative Physiol Ther. 2010;33:576–84. Jadad AR, Browman GP. The WHO analgesic ladder for cancer pain management. Stepping up the quality of its evaluation. JAMA. 1995;274:1870–3. Pinto RZ, Maher CG, Ferreira ML, Ferreira PH, Hancock M, Oliveira VC, et al. Drugs for relief of pain in patients with sciatica: systematic review and meta-analysis. BMJ. 2012;344:e497. Khoromi S, Cui L, Nackers L, Max MB. Morphine, nortriptyline and their combination vs. placebo in patients with chronic lumbar root pain. Pain. 2007;130:66–75. Radcliff K, Freedman M, Hilibrand A, Isaac R, Lurie JD, Zhao W, et al. Does opioid pain medication use affect the outcome of patients with lumbar disc herniation? Spine. 2013;38:E849–60. After decades of encouragement to increase the use of opioid medications in noncancer pain, several recent publications have highlighted various problems and side effects with these treatments. This study clearly adds to our knowledge on the limitation of opioid medications in lumbar radicular pain. Brötz D, Maschke E, Burkard S, Engel C, Mänz C, Ernemann U, et al. Is there a role for benzodiazepines in the management of lumbar disc prolapse with acute sciatica? J Pain. 2010;149:470–5. Attal N, Perrot S, Fermanian J, Bouhassira D. The neuropathic components of chronic low back pain: a prospective multicenter study using the DN4 Questionnaire. J Pain. 2011;12:1080–7. One of the only studies that clearly addresses the neuropathic component of lumbar radicular pain syndrome. A field that should deserve more attention in order to improve the current care. Perrot S, Javier R-M, Marty M, Le Jeunne C, Laroche F. Is there any evidence to support the use of anti-depressants in painful rheumatological conditions? Systematic review of pharmacologic and clinical studies. Rheumatology. 2008;47:1117–23. Khoromi S, Patsalides A, Parada S, Salehi V, Meegan JM, Max MB. Topiramate in chronic lumbar radicular pain. J Pain. 2005;6:829–36. Yildirim K, Sisecioglu M, Karatay S, et al. The effectiveness of gabapentin in patients with chronic radiculopathy. Pain Clin. 2003;15:213–8. Baron R, Freynhagen R, Tölle TR, Cloutier C, Leon T, Murphy TK, et al. The efficacy and safety of pregabalin in the treatment of neuropathic pain associated with chronic lumbosacral radiculopathy. J Pain. 2010;150:420–7.
Page 5 of 5, 452 40.
Bennett MI, Smith BH, Torrance N, Lee AJ. Can pain be more or less neuropathic? Comparison of symptom assessment tools with ratings of certainty by clinicians. Pain. 2006;122:289–94. 41. Finckh A, Zufferey P, Schurch M-A, Balagué F, Waldburger M, So AKL. Short-term efficacy of intravenous pulse glucocorticoids in acute discogenic sciatica. A randomized controlled trial. Spine. 2006;31:377–81. 42. Chou R, Qaseem A, Snow V, Casey D, Cross JT, Shekelle P, et al. Diagnosis and treatment of low back pain: a joint clinical practice guideline from the American College of Physicians and the American Pain Society. Ann Intern Med. 2007;147:478–91. 43. Houten JK, Errico TJ. Paraplegia after lumbosacral nerve root block: report of three cases. Spine J. 2002;2:70–5. 44. Quintero N, Laffont I, Bouhmidi L, Rech C, Schneider AE, Gavardin T, et al. Transforaminal epidural steroid injection and paraplegia: case report and bibliographic review. Ann Readapt Med Phys. 2006;49:242–7. 45. Kennedy DJ, Dreyfuss P, Aprill CN, Bogduk N. Paraplegia following image-guided transforaminal lumbar spine epidural steroid injection: two case reports. Pain Med. 2009;10:1389–94. 46. Wybier M, Gaudart S, Petrover D, Houdart E, Laredo J-D. Paraplegia complicating selective steroid injections of the lumbar spine. Report of five cases and review of the literature. Eur Radiol. 2010;20:181–9. 47. AFSSAPS. Risque de paraplégie/tétraplégie lié aux injections radioguidées de glucocorticoïdes au rachis lombaire ou cervical. Available at: http://ansm.sante.fr/var/ansm_site/storage/original/ application/b66ab66a89c8b30fc78c334142e91b3e.pdf. Accessed 27 Aug 2014. 48. Chang Chien GC, Candido KD, Knezevic NN. Digital subtraction angiography does not reliably prevent paraplegia associated with lumbar transforaminal epidural steroid injection. Pain Phys. 2012;15:515–23. 49.•• Lewis RA, Williams NH, Sutton AJ, Burton K, Din NU, Matar HE, et al. Comparative clinical effectiveness of management strategies for sciatica: systematic review and network meta-analyses. Spine J. 2013. doi:10.1016/j.spinee.2013.08.049. A novative statistical method that allows a full overview of all treatments that have been tested in randomized clinical studies and their “direct” comparison. A new way to reach interesting conclusions on best available treatments. 50. Genevay S, Finckh A, Payer M, Mezin F, Tessitore E, Gabay C, et al. Elevated levels of tumor necrosis factor-alpha in periradicular fat tissue in patients with radiculopathy from herniated disc. Spine. 2008;33:2041–6. 51. Pimentel DC, El Abd O, Benyamin RM, Buehler AM, Leite VF, Mazloomdoost D, et al. Anti-tumor necrosis factor antagonists in the treatment of low back pain and radiculopathy: a systematic review and meta-analysis. Pain Phys. 2014;17:E27–44. 52. Genevay S, Viatte S, Finckh A, Zufferey P, Balagué F, Gabay C. Adalimumab in severe and acute sciatica: a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2010;62:2339–46. 53. Genevay S, Finckh A, Zufferey P, Viatte S, Balagué F, Gabay C. Adalimumab in acute sciatica reduces the long-term need for surgery: a 3-year follow-up of a randomised double-blind placebocontrolled trial. Ann Rheum Dis. 2012;71:560–2. 54.•• Williams NH, Lewis R, Din NU, Matar HE, Fitzsimmons D, Phillips CJ, et al. A systematic review and meta-analysis of biological treatments targeting tumour necrosis factor α for sciatica. Eur Spine J. 2013;22:1921–35. A comprehensive analysis of the potential and the limitations of TNF inhibitors in radicular pain. 55. Leite VF, Buehler AM, El Abd O, Benyamin RM, Pimentel DC, Chen J, et al. Anti-nerve growth factor in the treatment of low back pain and radiculopathy: a systematic review and a meta-analysis. Pain Phys. 2014;17:E45–60.
NEUROPATHIC PAIN (E EISENBERG, SECTION EDITOR)
Conservative Treatments for Lumbar Radicular Pain Gregory Fleury & Michael J. Nissen & Stéphane Genevay
Published online: 18 September 2014 # Springer Science+Business Media New York 2014
Abstract Lumbar radicular pain is a frequent medical pathology and represents a significant burden on society. The diagnosis of sciatica is largely clinical, in the setting of a combination of radicular pain and neurologic deficits (motor, reflexes, and/or sensation) or a positive straight leg raise test. Imaging is generally not necessary for sciatica, except in the presence of warning signs or in the setting of persisting or worsening pain. The recommended first-line treatment has not yet been clearly established. The choice of a conservative treatment approach combined with simple analgesics in the initial stages seems to be reasonable. A detailed discussion with the patient is important to explain the fact that surgery may only be necessary in the event of pain persisting in excess of 3 months or because of the development or worsening of a neurologic deficit. More high quality studies are clearly required to assist the medical practitioner in knowing how best to treat this group of patients. Keywords Sciatica . Radicular leg pain . Radiculopathy . Herniated disc . Treatment . Pharmacotherapy
Introduction Lumbar radicular pain is generally referred to as sciatica. Although it is a widespread condition, the scientific literature is rather confusing, mainly because of the fact that it is a syndrome encompassing clinical symptoms and signs rather than a specific pathologic entity. In addition, in the absence of a widely accepted consensus definition [1], for decades This article is part of the Topical Collection on Neuropathic Pain G. Fleury : M. J. Nissen : S. Genevay (*) Division of Rheumatology, University Hospitals of Geneva, 26 Avenue de Beau-Séjour, 1211 Geneva 14, Switzerland e-mail: [email protected]
studies and systemic reviews failed to differentiate these patients from those with nonspecific low back pain [2–4]. There is, however, a need for better recognition of this condition, as it consumes a considerable proportion of health resources and is a major cost to society, particularly with regards to absenteeism [5]. Selim et al. [6] reported that patients with radicular symptoms have more pain than those with isolated low back pain and that they have a greater tendency to chronicity [7]. The management of this pathology is therefore a significant challenge for both general practitioners and specialists. It is generally accepted that treatment should be conservative for at least the first 2–3 months. Progressive significant motor weakness or the cauda equina syndrome are exceptions to this rule as most would advocate immediate surgical management. However, there are very few randomized studies comparing the different treatment strategies of the various clinical presentations of sciatica. This article aims to review the nonsurgical treatments for sciatica with particular focus on the commonly used pharmacologic treatments, as well as potential emerging therapies. According to a recent systematic review, sciatica has a prevalence of between 1.2 % and 43 % in the general population [8]. This broad range of prevalence highlights the lack of consensus toward a universally accepted definition! However, when diagnosis relies on physical examination, a prevalence of 4.8 % is reported [8]. The annual incidence is about 0.5 % in adults [9•]. Sciatica is commonly characterized by unilateral lower limb radicular pain (ie, pain radiating in a specific dermatome) and is often associated with neurologic symptoms such as numbness, loss of sensitivity, diminished reflexes, and motor weakness. Although several different etiologies may result in sciatica (Table 1), more than 90 % are related to lumbar disc herniation (DH) [11], which is defined as a localized displacement of disc material (nucleus pulpous and/or annulus fibrosis) beyond the normal margins of the intervertebral disc space [12••]. In the absence of widely
452, Page 2 of 5
Curr Pain Headache Rep (2014) 18:452
Table 1 Differential diagnosis of radicular pain not related to disc herniation Malignancy Infection Vascular compression Muscular compression Bony compression Epidural Gynecologic Metabolic
Metastatic, sarcoma, neuroma, hemangioblastoma Abscess, discitis, epiduritis Epidural thrombosis, abnormal pelvic venous plexus, gluteal artery pseudo-aneurysm Piriformis syndrome Degenerative spinal stenosis, foraminal stenosis, osteophytes of the sacroiliac joint Epidural lipomatosis, epidural adhesions (eg postoperative) Pelvic endometriosis, uterine fibroid Diabetic painful amyotrophy, alcoholic neuropathy
Adapted from: Stafford MA, Peng P, Hill DA. Sciatica: a review of history, epidemiology, pathogenesis, and the role of epidural steroid injection in management. Br J Anaesth. 2007;99:461–73 [10]
accepted classification criteria, we would advocate the use of the eligibility criteria used in the SPORT’s trial [13]: radicular pain associated with either a clinical sign of nerve root irritation, the straight leg raising (SLR) test (for the L5 or S1 nerve roots) or the reverse SLR (for the L3 or L4 nerve roots), or a neurologic deficit, either sensitive, reflex or motor strength, associated with a herniated disc at the level and side corresponding to the radicular pain. Of note, the SLR test has a sensitivity of 92 % and a specificity of 28 % whereas the crossed SLR test showed a high specificity (90 %) but with low sensitivity (28 %) [14]. No figures have been reported for the reverse SLR. Although the exact pathophysiology remains unclear, there is certainly an element attributable to local mechanical effects of direct contact of the herniated disc with the nerve root, as well as an inflammatory component with potential activation of the immune system [15•]. Of note, compression is not an absolute requirement and the size of the herniated disc doesn’t influence the clinical presentation [15•]. Risk factors have not clearly been identified, although obesity, heavy manual work, and smoking have all been proposed [16]. In a recent study, the use of tobacco was the only risk factor found to be associated with an elevated risk of hospitalization for sciatica [17].
back. The fear of movement or kinesiophobia is a factor that has been linked to a less favorable outcome [18] and needs to be addressed. The causes of sciatica and the natural course of the disease should also be discussed at an early stage [11]. Imaging is not necessary initially, unless there are symptoms of other potentially serious diseases (ie, infection or tumor) or if the symptoms worsen or persist. This is an important point to discuss with the patient who will often expect an MRI to be performed at the first presentation. Based on well conducted randomized control trials (RCT) [19, 20], several systematic reviews [2, 11, 21] found no evidence for a role of bed rest in sciatica. However, in contrast to acute low back pain, no deleterious effects have been reported [2]. Nevertheless, in contrast with low back pain, there is no evidence that physical activity is beneficial for these patients [22]. Amongst the different physiotherapy techniques advocated, traction has been suggested by many, but a systematic review failed to confirm a positive effect of either intermittent or continuous traction compared with placebo in terms of pain relief and returning to work [23, 24]. In a single RCT, transcutaneous electrical nerve stimulation (TENS), often used for neuropathic pain, showed some efficacy with a reduction of the radicular component of pain [25]. In a systematic review published in 2007, Luijsterburg et al. reported that active exercises provided by physiotherapists were not more effective than usual care [26]. Since this review, to the best of our knowledge, only 2 RCT have been published on the effect of physiotherapy in sciatica. In the first study, the addition of exercises provided under the guidance of a physiotherapist in addition to the general practitioner’s care, provided a better improvement in terms of “patient perceived global effect” compared with general practitioner’s care alone [27]. The second study demonstrated that symptom-guided exercises (also known as “McKenzie” method) produced a slightly better outcome when compared with sham exercises [28]. Manipulations in the context of a herniated disc have been controversial. Recently, in a randomized trial, McMorland et al. reported that chiropractic spinal manipulation was as effective as microdiscectomy at 1-year follow-up [29]. However, more than a third of the patients in the manipulation group crossed over to the surgery arm with a subsequent significant improvement. Nociceptive Pain Treatments
Treatments Nonpharmacologic Treatments The first step is an interactive discussion between the therapist and the patient, which will establish the foundation for successful therapy. It is critical to listen to the concerns and fears of the patient at an early stage, in order to address their concerns that the sciatica could represent a broken or weak
In the acute phase, sciatic pain is considered to be a predominantly nociceptive pain [23] and is currently being treated in a similar way to low back pain [15•], with adaptation of the intensity of the treatment according to the intensity of pain and following the 3 steps of the WHO recommendations [30]. However, there is a paucity of good quality studies to support this approach. There are no studies evaluating the efficacy of acetaminophen in sciatica. Mixed results have been found for
Curr Pain Headache Rep (2014) 18:452
NSAIDs and Pinto et al. in their systematic review concluded that there was limited support for the use of NSAIDs to relieve pain in the short term with no study demonstrating the superiority of one molecule over another [31]. As for opioid analgesics, no study has been published concerning the use of tramadol. One randomized controlled trial in chronic sciatica found no effect of morphine alone or in combination with nortriptyline [32]. More recently, in a post hoc analysis of the SPORT trial with inclusion of more than 1000 patients, Radcliff et al. [33•] found that the use of opioids (prescribed in slightly more than half the patients) was associated with worse baseline pain and quality of life. More interestingly, they observed an increased crossover to surgical treatment, whereas a decrease would have been expected in the case of significant efficacy. In a RCT conducted in hospitalized patients, the well-known benzodiazepine diazepam, often prescribed for muscle relaxation showed no effect, and conversely was associated with a prolongation of hospital stay because of side effects [34]. Neuropathic Pain Treatment When sciatic pain becomes chronic, a neuropathic component is frequently reported [35•] and neuropathic pain treatments could be considered. Antidepressants have been advocated for the treatment of back pain in chronic sciatica [36], however, neither topiramate [37] or nortriptyline [32] have demonstrated efficacy in chronic sciatic pain. Intriguingly, a large beneficial effect was reported in a RCT using gabapentin (900 to 3600 mg/d) [38], whereas no effect was observed in a more recent RCT with pregabalin [39], albeit using a nonconventional design. This surprising lack of efficacy might be due to the difficulty of the clinician in selecting appropriate patients [40]. Corticosteroids Corticosteroids have been used for sciatica for many decades and by various routes of administration (oral, IM, and IV) although their role remains subject to controversy. In a systematic review, Roncoroni et al. in 2011 [9•] reported that the systemic use of steroids was not superior to placebo in preventing work absenteeism and did not reduce the requirement for analgesics, but conversely resulted in an important increase in side effects (number needed to harm: 20), including an increased risk for surgery. More recently, Pinto et al. confirmed the lack of efficacy of oral steroids in sciatica but concluded a small beneficial effect of steroids in the short term when used intravenously [31]. This result referred mainly to the study published by Finckh et al. [41] who reported a transitory effect of only 48 hours of benefit in terms of leg pain following IV injection of 500 mg of solumedrol. Finally, the American Pain Society does not recommend the use of
Page 3 of 5, 452
steroids for sciatica because of a lack of evidence for their efficacy [42]. Turning now to the subject of corticosteroid injections within and adjacent to the spinal canal. Transforaminal injection is the most effective route of administration of corticosteroid into the spinal canal [15•] and it is the one recommended by the North American Spine Society for its short-term effect, although there is no evidence that it decreases the requirement for surgery [12••]. Following several case reports of paraplegia because of spinal cord infarction after transforaminal injection [43–46], the French National Health Security Agency has published a warning stating that alternative methods of injection should be preferred (translaminar or caudal), particularly in patients with prior spinal surgery [47]. Of note, digital subtraction angiography and use of an anesthetic test dose did not prevent these catastrophic events [48]. In summary, we advocate the use of spinal injection initially via a caudal or translaminar route, reserving use of the transforaminal approach for cases resistant to other routes of administration and after patients have been fully informed about the potential risks. Very recently, the results of a network meta-analysis for the treatment of sciatica, were published [49••]. This statistical method allows the simultaneous comparison of all treatment strategies and indirect comparisons of these treatments. The findings supported the effectiveness of nonopioid medications and epidural injection along with disc surgery whereas bed rest, education/advice (when used alone), NSAIDs, exercise therapy, traction and percutaneous discectomy were not supported by the evidence. Experimental Pharmacologic Treatments In recent years, new pharmacologic agents have been investigated. As TNF-alpha appeared to be a key molecule in animal models of sciatica [15•] and was found at increased levels around the nerve roots of patients suffering from sciatica [50], TNF inhibitors have been the most widely studied of the various biological agents. Several randomized studies using epidural injection of etanercept, a fusion protein containing a TNF-alpha receptor, have been published. A meta-analysis found low evidence that epidural etanercept has a low-tomoderate effect size [51]. A unique RCT with subcutaneous injection of adalimumab, a monoclonal antibody against TNFalpha, found a small benefit in terms of pain, as well as a decreased need for surgery at 6 months [52] that was confirmed at 3 years follow-up [53]. A second meta-analysis concluded that there was currently insufficient evidence to recommend the use of TNF-alpha inhibitors for sciatica, but sufficient evidence to suggest that larger RCTs are needed [54••]. The use of Anti-Nerve Growth Factor is another potentially interesting approach to treat sciatica. A recent meta-analysis
452, Page 4 of 5
was conducted encompassing 3 RCTs. A short-term (16 weeks) effect on pain and functional impairment [55] was found, but it was small and not clinically significant. In addition, there was an increased level of side effects in the treated group and more specifically the presence of neurologic side effects such as headache, hyperesthesia, and abnormal peripheral sensation.
Conclusions Radicular pain because of a herniated disc needs to be identified and not confused with mechanical low back pain. Not only is the course of the disease different but, according to available data, treatment effectiveness is also different. Despite the paucity of good quality trials, conservative treatment using analgesics, neuropathic pain treatments, and epidural corticosteroids remain the core of management. Surgery should be proposed when disabling pain persists despite 3 months of standard care or in the setting of major neurologic complications. Compliance with Ethics Guidelines Conflict of Interest Gregory Fleury and Michael J. Nissen declare that that have no conflict of interest. Stéphane Genevay has received an unrestricted scientific grant from Abbott. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.
References Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance 1.
2.
3.
4.
Genevay S, Atlas SJ, Katz JN. Variation in eligibility criteria from studies of radiculopathy due to a herniated disc and of neurogenic claudication due to lumbar spinal stenosis: a structured literature review. Spine. 2010;35:803–11. Hagen KB, Jamtvedt G, Hilde G, Winnem MF. The updated Cochrane review of bed rest for low back pain and sciatica. Spine. 2005;30:542–6. Goh L, Bawendi A, Samanta J, Samanta A. An evidence-based approach to the management of low back pain and sciatica: how the evidence is applied in clinical cases. Musculoskelet Care. 2003;1: 119–30. Airaksinen O, Brox JI, Cedraschi C, Hildebrandt J, Klaber-Moffett J, Kovacs F, et al. Chapter 4. European guidelines for the management of chronic nonspecific low back pain. Eur Spine J. 2006;15 Suppl 2:S192–300.
Curr Pain Headache Rep (2014) 18:452 5.
Awad JN, Moskovich R. Lumbar disc herniations: surgical vs nonsurgical treatment. Clin Orthop Relat Res. 2006;443:183–97. 6. Selim AJ, Ren XS, Fincke G, Deyo RA, Rogers W, Miller D, et al. The importance of radiating leg pain in assessing health outcomes among patients with low back pain. Results from the Veterans Health Study. Spine. 1998;23:470–4. 7. Chou R, Shekelle P. Will this patient develop persistent disabling low back pain? JAMA. 2010;303:1295–302. 8. Konstantinou K, Dunn KM. Sciatica: review of epidemiological studies and prevalence estimates. Spine. 2008;33:2464–72. 9.• Roncoroni C, Baillet A, Durand M, Gaudin P, Juvin R. Efficacy and tolerance of systemic steroids in sciatica: a systematic review and meta-analysis. Rheumatology. 2011;50:1603–11. Systemic steroids are often prescribed in sciatica as they are easier to deliver than Spine. injections. This study put into question their efficacy and underline the importance of their side effects. 10. Stafford MA, Peng P, Hill DA. Sciatica: a review of history, epidemiology, pathogenesis, and the role of epidural steroid injection in management. Br J Anaesth. 2007;99:461–73. 11. Koes BW, van Tulder MW, Peul WC. Diagnosis and treatment of sciatica. BMJ. 2007;334:1313–7. 12.•• Kreiner DS, Hwang SW, Easa JE, Resnick DK, Baisden JL, Bess S, et al. An evidence-based clinical guideline for the diagnosis and treatment of lumbar disc herniation with radiculopathy. Spine J. 2014;14: 180–91. A useful guideline to help clinicians in the treatment of lumbar radicular pain because of disc herniation. This recent and comprehensive review also underlines the lack of literature on many important questions related to the treatment of this frequent syndrome. 13. Weinstein JN, Tosteson TD, Lurie JD, Tosteson ANA, Hanscom B, Skinner JS, et al. Surgical vs nonoperative treatment for lumbar disk herniation: the Spine Patient Outcomes Research Trial (SPORT): a randomized trial. JAMA. 2006;296:2441–50. 14. Van der Windt DA, Simons E, Riphagen II, Ammendolia C, Verhagen AP, Laslett M, et al. Physical examination for lumbar radiculopathy due to disc herniation in patients with low-back pain. Cochrane Database Syst Rev. 2010. doi:10.1002/14651858.CD007431. 15.• Valat J-P, Genevay S, Marty M, Rozenberg S, Koes B. Sciatica. Best Pract Res Clin Rheumatol. 2010;24:241–52. A comprehensive review on both pathophysiology and treatment for lumbar radicular pain because of disc herniation. 16. Karjalainen U, Paananen M, Okuloff A, Taimela S, Auvinen J, Männikkö M, et al. Role of environmental factors and history of low back pain in sciatica symptoms among Finnish adolescents. Spine. 2013;38:1105–11. 17. Rivinoja AE, Paananen MV, Taimela SP, Solovieva S, Okuloff A, Zitting P, et al. Sports, smoking, and overweight during adolescence as predictors of sciatica in adulthood: a 28-year follow-up study of a birth cohort. Am J Epidemiol. 2011;173:890–7. 18. Haugen AJ, Brox JI, Grøvle L, Keller A, Natvig B, Soldal D, et al. Prognostic factors for non-success in patients with sciatica and disc herniation. BMC Musculoskelet Disord. 2012;13:183. 19. Vroomen PC, de Krom MC, Wilmink JT, Kester AD, Knottnerus JA. Lack of effectiveness of bed rest for sciatica. N Engl J Med. 1999;340:418–23. 20. Hofstee DJ, Gijtenbeek JMM, Hoogland PH, van Houwelingen HC, Kloet A, Lötters F, et al. Westeinde sciatica trial: randomized controlled study of bed rest and physiotherapy for acute sciatica. J Neurosurg. 2002;96:45–9. 21. Luijsterburg PA, Verhagen AP, Ostelo RWJG, van Os AG, Peul WC, Koes BW. Effectiveness of conservative treatments for the lumbosacral radicular syndrome: a systematic review. Eur Spine J. 2007;16:881–99. 22. Dahm KT, Brurberg KG, Jamtvedt G, Hagen KB. Advice to rest in bed vs advice to stay active for acute low-back pain and sciatica. Cochrane Database Syst Rev. 2010. doi:10.1002/14651858. CD007612.
Curr Pain Headache Rep (2014) 18:452 23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.•
34.
35.•
36.
37. 38.
39.
Wegner I, Widyahening IS, van Tulder MW, Blomberg SEI, de Vet HC, Brønfort G, et al. Traction for low-back pain with or without sciatica. Cochrane Database Syst Rev. 2013. doi:10.1002/ 14651858.CD003010 Clarke JA, van Tulder MW, Blomberg SEI, de Vet HCW, van der Heijden GJ, Brønfort G, Bouter LM. Traction for low-back pain with or without sciatica. Cochrane Database Syst Rev. 2007:Issue 2. Art. No.: CD003010. doi:10.1002/14651858.CD003010 Ghoname EA, White PF, Ahmed HE, Hamza MA, Craig WF, Noe CE. Percutaneous electrical nerve stimulation: an alternative to TENS in the management of sciatica. Pain. 1999;83:193–9. Luijsterburg PA, Lamers LM, Verhagen AP, Ostelo RWJG, van den Hoogen HJMM, Peul WC, et al. Cost-effectiveness of physical therapy and general practitioner care for sciatica. Spine. 2007;32: 1942–8. Luijsterburg PA, Verhagen AP, Ostelo RWJG, van den Hoogen HJMM, Peul WC, Avezaat CJJ, et al. Physical therapy plus general practitioners’ care vs general practitioners’ care alone for sciatica: a randomised clinical trial with a 12-month follow-up. Eur Spine J. 2008;17:509–17. Albert HB, Manniche C. The efficacy of systematic active conservative treatment for patients with severe sciatica: a single-blind, randomized, clinical, controlled trial. Spine. 2012;37:531–42. McMorland G, Suter E, Casha S, du Plessis SJ, Hurlbert RJ. Manipulation or microdiskectomy for sciatica? A prospective randomized clinical study. National University of Health Sciences. J Manipulative Physiol Ther. 2010;33:576–84. Jadad AR, Browman GP. The WHO analgesic ladder for cancer pain management. Stepping up the quality of its evaluation. JAMA. 1995;274:1870–3. Pinto RZ, Maher CG, Ferreira ML, Ferreira PH, Hancock M, Oliveira VC, et al. Drugs for relief of pain in patients with sciatica: systematic review and meta-analysis. BMJ. 2012;344:e497. Khoromi S, Cui L, Nackers L, Max MB. Morphine, nortriptyline and their combination vs. placebo in patients with chronic lumbar root pain. Pain. 2007;130:66–75. Radcliff K, Freedman M, Hilibrand A, Isaac R, Lurie JD, Zhao W, et al. Does opioid pain medication use affect the outcome of patients with lumbar disc herniation? Spine. 2013;38:E849–60. After decades of encouragement to increase the use of opioid medications in noncancer pain, several recent publications have highlighted various problems and side effects with these treatments. This study clearly adds to our knowledge on the limitation of opioid medications in lumbar radicular pain. Brötz D, Maschke E, Burkard S, Engel C, Mänz C, Ernemann U, et al. Is there a role for benzodiazepines in the management of lumbar disc prolapse with acute sciatica? J Pain. 2010;149:470–5. Attal N, Perrot S, Fermanian J, Bouhassira D. The neuropathic components of chronic low back pain: a prospective multicenter study using the DN4 Questionnaire. J Pain. 2011;12:1080–7. One of the only studies that clearly addresses the neuropathic component of lumbar radicular pain syndrome. A field that should deserve more attention in order to improve the current care. Perrot S, Javier R-M, Marty M, Le Jeunne C, Laroche F. Is there any evidence to support the use of anti-depressants in painful rheumatological conditions? Systematic review of pharmacologic and clinical studies. Rheumatology. 2008;47:1117–23. Khoromi S, Patsalides A, Parada S, Salehi V, Meegan JM, Max MB. Topiramate in chronic lumbar radicular pain. J Pain. 2005;6:829–36. Yildirim K, Sisecioglu M, Karatay S, et al. The effectiveness of gabapentin in patients with chronic radiculopathy. Pain Clin. 2003;15:213–8. Baron R, Freynhagen R, Tölle TR, Cloutier C, Leon T, Murphy TK, et al. The efficacy and safety of pregabalin in the treatment of neuropathic pain associated with chronic lumbosacral radiculopathy. J Pain. 2010;150:420–7.
Page 5 of 5, 452 40.
Bennett MI, Smith BH, Torrance N, Lee AJ. Can pain be more or less neuropathic? Comparison of symptom assessment tools with ratings of certainty by clinicians. Pain. 2006;122:289–94. 41. Finckh A, Zufferey P, Schurch M-A, Balagué F, Waldburger M, So AKL. Short-term efficacy of intravenous pulse glucocorticoids in acute discogenic sciatica. A randomized controlled trial. Spine. 2006;31:377–81. 42. Chou R, Qaseem A, Snow V, Casey D, Cross JT, Shekelle P, et al. Diagnosis and treatment of low back pain: a joint clinical practice guideline from the American College of Physicians and the American Pain Society. Ann Intern Med. 2007;147:478–91. 43. Houten JK, Errico TJ. Paraplegia after lumbosacral nerve root block: report of three cases. Spine J. 2002;2:70–5. 44. Quintero N, Laffont I, Bouhmidi L, Rech C, Schneider AE, Gavardin T, et al. Transforaminal epidural steroid injection and paraplegia: case report and bibliographic review. Ann Readapt Med Phys. 2006;49:242–7. 45. Kennedy DJ, Dreyfuss P, Aprill CN, Bogduk N. Paraplegia following image-guided transforaminal lumbar spine epidural steroid injection: two case reports. Pain Med. 2009;10:1389–94. 46. Wybier M, Gaudart S, Petrover D, Houdart E, Laredo J-D. Paraplegia complicating selective steroid injections of the lumbar spine. Report of five cases and review of the literature. Eur Radiol. 2010;20:181–9. 47. AFSSAPS. Risque de paraplégie/tétraplégie lié aux injections radioguidées de glucocorticoïdes au rachis lombaire ou cervical. Available at: http://ansm.sante.fr/var/ansm_site/storage/original/ application/b66ab66a89c8b30fc78c334142e91b3e.pdf. Accessed 27 Aug 2014. 48. Chang Chien GC, Candido KD, Knezevic NN. Digital subtraction angiography does not reliably prevent paraplegia associated with lumbar transforaminal epidural steroid injection. Pain Phys. 2012;15:515–23. 49.•• Lewis RA, Williams NH, Sutton AJ, Burton K, Din NU, Matar HE, et al. Comparative clinical effectiveness of management strategies for sciatica: systematic review and network meta-analyses. Spine J. 2013. doi:10.1016/j.spinee.2013.08.049. A novative statistical method that allows a full overview of all treatments that have been tested in randomized clinical studies and their “direct” comparison. A new way to reach interesting conclusions on best available treatments. 50. Genevay S, Finckh A, Payer M, Mezin F, Tessitore E, Gabay C, et al. Elevated levels of tumor necrosis factor-alpha in periradicular fat tissue in patients with radiculopathy from herniated disc. Spine. 2008;33:2041–6. 51. Pimentel DC, El Abd O, Benyamin RM, Buehler AM, Leite VF, Mazloomdoost D, et al. Anti-tumor necrosis factor antagonists in the treatment of low back pain and radiculopathy: a systematic review and meta-analysis. Pain Phys. 2014;17:E27–44. 52. Genevay S, Viatte S, Finckh A, Zufferey P, Balagué F, Gabay C. Adalimumab in severe and acute sciatica: a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2010;62:2339–46. 53. Genevay S, Finckh A, Zufferey P, Viatte S, Balagué F, Gabay C. Adalimumab in acute sciatica reduces the long-term need for surgery: a 3-year follow-up of a randomised double-blind placebocontrolled trial. Ann Rheum Dis. 2012;71:560–2. 54.•• Williams NH, Lewis R, Din NU, Matar HE, Fitzsimmons D, Phillips CJ, et al. A systematic review and meta-analysis of biological treatments targeting tumour necrosis factor α for sciatica. Eur Spine J. 2013;22:1921–35. A comprehensive analysis of the potential and the limitations of TNF inhibitors in radicular pain. 55. Leite VF, Buehler AM, El Abd O, Benyamin RM, Pimentel DC, Chen J, et al. Anti-nerve growth factor in the treatment of low back pain and radiculopathy: a systematic review and a meta-analysis. Pain Phys. 2014;17:E45–60.
