Radiculopathy

The selective nerve root block was developed as a technique to identify the source of intractable radicular symptoms, particularly when the clinical symptoms are not well localized, and imaging studies indicate multilevel degenerative changes with possible compression of several roots. While these techniques may be used for surgical decision making, there are only limited data (primarily retrospective) to support their use for prediction. Therefore, the use of diagnostic or prognostic selective nerve root blocks needs to be put in a careful individualized context.

Retrospective studies have investigated the ability of selective spinal nerve blocks to diagnose disease and to predict surgical outcome. The positive predictive value (fraction of patients with injection indicating radiculopathy, in whom surgery confirmed radicular pathology at the level indicated by the test) ranged from 87% to 100%. The negative predictive values (percentage of patients with a negative injection test and confirmed at the surgery to have normal nerve roots) were reported as 20% and 38% of the small number of patients operated upon, despite negative tests. Bear in mind that such “diagnostic” injections are typically only considered when the information will be acted upon, meaning surgical intervention is viewed as a viable treatment option.

The role of injected steroids in addition to local anesthetic in a diagnostic block is a controversial topic. However, a retrospective report of the ability of a steroid-containing injection of the spinal nerve to predict surgical outcome showed that the false positive rate (percentage of patients with failed surgery who had a favorable response to injection) was 5%, and the false negative rate (percentage of surgical successes who had no response to steroids) was 35%. These observations suggest that patients with radicular pain who are unlikely to benefit from surgery can be reliably identified by a lack of response to epidural steroid injections (ESIs), but some patients who may benefit from surgery could be missed by this diagnostic test.

Peripheral Neuropathic Pain

The main diagnostic tools in peripheral neuropathies are electromyography, ultrasonography, computed tomography, and/or magnetic resonance imaging, which are interpreted in the context of clinical findings. At times, an injection might provide valuable information if more standard testing has led to ambiguity. A case report on the role of diagnostic ultrasound-guided selective common peroneal nerve block in a patient with classic neuropathic pain after below-knee amputation suggested that successful diagnostic, ultrasound-guided, selective peripheral nerve block may be performed to help in the diagnosis and subsequent surgical resection of a painful neuroma to relieve severe neuropathic pain. A multicenter retrospective study examined the role of diagnostic nerve blocks in evaluating pulsed radiofrequency (PRF) for occipital neuralgia. It reported that about half of the subjects experienced a positive outcome (≥50% pain relief coupled with procedure satisfaction lasting at least 3 months), and variables associated with a positive outcome included a traumatic inciting event and lower diagnostic block volumes.

Complex Regional Pain Syndrome

Given the possible involvement of the sympathetic nervous system in the initiation or maintenance of pain in CRPS, sympathetic blocks have a unique and long tradition in the dual roles of both diagnostic and therapeutic tools in the management of CRPS. Despite this history, the data supporting them is limited with weak evidence to support the diagnostic role of the classic stellate ganglion block (SGB) and lumbar sympathetic block (LSB) to differentiate sympathetically independent pain from sympathetically maintained pain (SMP).

Specific comments on the value of diagnostic nerve blocks are in Box 78.1 .

Summary: Diagnostic Value of Neural Blockade

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  Diagnostic nerve blocks have a potential role in the management of chronic neuropathic pain, as they can help determine the anatomical source of pain, and a target for treatments.

  
  
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  Specificity of the diagnostic nerve blocks may be enhanced by advanced imaging guidance using the lowest volume of injectate, preferably with local anesthetic alone rather than steroids.

  
  
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  The classic SGB and LSB that remain in most CRPS treatment algorithms in order to differentiate sympathetically independent pain from sympathetically maintained pain need to be interpreted with caution.

Peripheral Compression or Trauma-Related Neuropathic Pain

Perineural steroids are often used to treat chronic peripheral NP that is secondary to trauma or compression, and Morton’s neuroma. Some randomized controlled trials (RCTs) showed that combining steroids with local anesthetic (LA) may increase efficacy, and LA injections without steroids may confer long-term analgesic benefits. A recent systemic review concluded that the change in mean pain scores following the injection of steroids represented a modest, but significant, reduction from baseline (25%). The analgesia resulting from steroid injection is possibly dose-dependent. A double-blind, placebo-controlled study in patients with peripheral nerve compression or trauma-related NP showed that 40–80 mg of methylprednisolone or triamcinolone (these steroids are equipotent) had a beneficial effect in reducing pain at 1–3 months after injection when compared with LA injection or Conventional Medical Management (i.e., no injections). A larger reduction in pain scores was observed in RCTs that used higher doses of steroids (methylprednisolone 80 mg) and recorded pain scores at 3 months, when compared with trials that used lower doses of steroids (methylprednisolone or triamcinolone 40 mg) and recorded pain scores earlier (at 1–2 months). Studies with a high risk of bias were associated with a significant analgesic effect in favor of perineural steroids. Other studies indicate that the placebo analgesic effect is strong and that some of the analgesic benefits from perineurally injected steroids may be due to systemic uptake of the drug. Multiple subsequent injections are probably justified if substantial clinical benefit is obtained from the first injection; however, there is no evidence to support the contention that multiple injections will generate long-term relief.

Carpal tunnel syndrome is a common focal peripheral mononeuropathy caused by compression of the median nerve in the carpal tunnel at the wrist. Local anesthetic and steroid injections are commonly used to provide short-term symptomatic relief and to improve functional status as a step before more definite surgical decompression. This approach is supported by three high-quality RCTs: Clinical improvement for carpal tunnel syndrome at 1 month or less following local corticosteroids was demonstrated in a total of 141 participants compared with placebo injection, and significantly more improvement was observed in the corticosteroid injection group compared with the oral corticosteroid group within 8 weeks. Although more than one (two injections vs. one) injection of local corticosteroid did not provide further clinical improvement, prior local steroid injection does not prejudice the outcome of subsequent surgery.

Technically, more accurate localization of the median nerve with ultrasound guidance might lead to better outcomes. A Bayesian network meta-analysis of 10 studies with 633 patients compared the clinical effectiveness of local corticosteroid injections using the distal to flexor crease approach, the proximal to flexor crease approach, an ultrasound-guided in-plane injection, and an ultrasound-guided out-of-plane injection. Based on the clinical response, the change in symptom severity scale, and the change in the functional status scale before or near 8 weeks, the study concluded that the ultrasound-guided in-plane approach was the most effective among the above four injection techniques for carpal tunnel syndrome.

The prognostic value of local corticosteroid injections in predicting surgical outcomes in carpal tunnel syndrome was evaluated in a prospective study, which concluded that longer relief of symptoms after steroid injection correlated with better results of surgical treatment.

The effectiveness of intradermal injection of botulinum neurotoxin-A (BTX-A) for either surgical trauma-related or nonsurgical trauma-related nerve injuries was also studied. A randomized, prospective, double-blind, parallel group study in 25 patients assessed the effectiveness of intradermal injection of BTX A and reported significant improvement in average pain scores, brush allodynia, and cold pain threshold despite transiently aggravating immediate postprocedural pain.

Herpes Zoster

Studies of neural blockade in herpes zoster vary in the method, number, frequency, and duration of the blocks, and hence, are difficult to interpret. An RCT suggested that epidural blocks with local anesthetics combined with steroids soon after the onset of herpes zoster can result in decreased pain and allodynia. Another RCT reported that a single epidural injection of methylprednisolone and bupivacaine within 7 days of the onset of herpes zoster resulted in a modest benefit at 1 month (48% with pain in epidural steroid group vs. 58% with standard therapy). However, the prevalence of chronic pain over a 6-month follow-up period was not significantly reduced.

An RCT found that repetitive paravertebral injections (the paravertebral block with local anesthetics and steroids every 48 hours for 1 week plus acyclovir and analgesics) for acute herpes zoster resulted in only 13% of patients reporting zoster-related pain versus 45% in participants allocated to standard therapy (acyclovir and analgesics) at 1 month posttherapy. At 3, 6, and 12 months posttherapy, the incidence of PHN continued to be significantly lower in the paravertebral group than in the standard therapy group.

The results of RCTs suggest that repetitive epidural injections of local anesthetics and steroids early in herpes zoster may prevent PHN. These results are consistent with the results of several previous observational and cohort studies evaluating epidural local anesthetics alone or combined with steroids in herpes zoster.

Postherpetic Neuralgia

The literature on the efficacy of intrathecal methylprednisolone acetate (IT MPA) in NP patients is contradictory in three published RCTs. In the first small study in which 25 patients were divided into two arms, IT administration of MPA was more effective than epidural administration. Later, the same researchers reported the efficacy of four IT injections of MPA and lidocaine (89 subjects) performed over a 1-month period was superior compared with lidocaine alone (91 subjects) and a no-treatment control group (90 subjects) on 1–2 years follow-up. In order to confirm the results obtained from this trial, an independent research group attempted to replicate the findings. This trial was terminated early because an increase in pain was experienced at 8 weeks in all six patients randomized to IT MPA compared to one of four people in the control group. The lack of reproducibility of the results of this single RCT, along with lack of biological plausibility and the potential risks of adhesive arachnoiditis and fungal meningitis, have raised concerns over the use of IT MPA.

Several nonrandomized trials assessing sympathetic blockade in PHN have failed to demonstrate any benefit, and since there are very few data available to suggest a beneficial effect, it is difficult to recommend this as a viable treatment option.

In contrast, two double-blind, randomized studies support the efficacy of BTX-A in the treatment of PHN. The first study compared subcutaneous, gridlike, 1-cm interval injections of BTX-A, lidocaine, and saline (20 people in each of the three groups) into the region of tactile allodynia, and reported better pain relief, improved sleep hours, and reduced opioid consumptions in the BTX-A group over a 3-month follow-up. The favorable outcomes—improvement in visual analogue scale (VAS) pain score and quality of sleep—were reproduced in a subsequent study comparing the effect of subcutaneous, “chessboard manner” injection of BTX-A with placebo in 30 adult subjects with PHN. The efficacy of BTX-A treatment for PHN from blinded observations are further supported by two retrospective observational studies in small numbers of patients.

Lumbosacral and Cervical Radiculopathy

An epidural injection of steroids to treat radicular pain can be accomplished by many techniques with varied success and risks. The most commonly studied approaches are the interlaminar (IL), transforaminal (TF), and caudal routes. A comparative study among IL, TF, and caudal steroid administration concluded that the TF route is more effective than the caudal or IL routes. Using a TF approach, the injectate spreads to the ventral epidural space in almost all cases (close to the intervertebral disk), while the injectate using the IL approach can miss the targeted ventral epidural space in up to 40% of cases. Three systematic reviews and meta-analysis of RCTs concluded that a TF ESI offered short-term positive pain-reducing benefits (>2 weeks but <12 months) for patients with acute or subacute radicular pain. A comprehensive evidence-based review of RCTs on ESIs concluded that a modest benefit lasting up to 3 months was more likely when the TF technique was used (>70%) compared to the caudal (60%) and interlaminar (50%) techniques. In addition, the specialty of the author heavily influenced the results of both RCTs and review articles, with greater than 75% of RCTs and reviews authored by pain physicians being positive, compared to only 30% of RCTs and review articles conducted by nonpain physicians. In light of the potential catastrophic complications associated with the TF approach, the parasagittal interlaminar route was investigated in a double-blind RCT and found to result in comparable ventral epidural spread, pain relief, and functional improvement, while being associated with a lower risk of complications. Factors other than route may be associated with a less robust response to ESI. In a prospective cohort study, pain duration greater than 12 months, prior surgery, and heightened anxiety all decreased the odds of achieving a minimum clinically important difference in the Oswestry Disability Index 3 months after lumbar epidural steroids injection (LESI).

Interestingly, ESIs might represent a relatively safe and inexpensive option to facilitate functional recovery or avoid surgery. A double-blind RCT, authored by an orthopedic spine group, evaluated the operative rate in surgically amenable patients with herniated disk or spinal stenosis. It found that 29% of patients in the ESI group underwent surgery, which favorably compared with a 67% operative rate in the control group without ESI at follow-up periods ranging between 13 and 28 months; the avoidance of surgery persisted in most patients available at a subsequent 5-year follow-up. A recent meta-analysis and systematic review of randomized trials evaluating the efficacy of ESI found that epidural steroids have a small preventive effect on the need for surgery in the short term (<1 year), but not the long term. Another orthopedic RCT performed in 200 patients who were followed for 2 years after lumbar discectomy reported a 2-day reduction in hospital stay (from 8 to 6 days, P = .0001) and a reduction in the number of patients with neurological signs (70% vs. 44%, P = .0004) in the group who received ESI following discectomy, although no difference in reoperation rates was noted.

Failed Back Surgery Syndrome With Prominent Radicular Symptoms

Persistent pain after spinal surgery, often referred to as FBSS, represents an important and heterogeneous group of chronic pain patients, many of whom have an NP component with a variety of potential pathophysiologic mechanisms. Patients with prominent radicular symptoms associated with FBSS represent one group who are frequently referred for ESIs. Unfortunately, there are no high-quality studies of ESIs specifically in this patient population, but a prospective web-based registry study suggests decreased efficacy in these patients. This study of 239 consecutive patients undergoing LESI for back-related disability, back pain, and leg pain associated with degenerative spine pathology concluded that prior surgery decreased the odds of achieving a minimum clinically important difference in the Oswestry Disability Index after LESI.

Complex Regional Pain Syndrome

Based on the evidence for possible involvement of the sympathetic nervous system in the initiation or maintenance of pain in CRPS, a sympathetic nerve block (SNB) is commonly used for pain relief, and to provide a “window of opportunity” for more aggressive rehabilitation therapy. The potential benefits of sympathetic blockade with local anesthetics in patients with CRPS have been systematically reviewed. In patients who respond favorably to an SNB, the pain relief generally outlasts the effects of the local anesthetic and may be long lasting in some cases. A randomized crossover study of seven subjects showed modest benefits 3 days after a local anesthetic SNB. An RCT of SGB versus “active control” (in the form of guanethidine IV regional block) reported improvement in both groups, but without significant differences between groups. A long-term, randomized, double-blinded, active-control study evaluated the efficacy of a thoracic sympathetic block (TSB) for upper limb type I CRPS at the 12-month follow-up in 36 patients. Scores from average pain items, pain dimensions (McGill Pain Questionnaire), evoked-pain symptom subscores, and depression scores were significantly lower in the TSB group compared to the control group. Furthermore, a case series of 25 subjects who underwent three SGBs at weekly intervals for upper-extremity CRPS reported that 40% of patients had complete pain relief, 36% had partial pain relief, and 24% had no pain relief over a 6-month observation period.

Given the role of the proliferation of adrenergic receptors and depolarization of nociceptors by increasing catecholamine release at the cholinergic nerve terminals as a possible molecular basis underlying SMP, BTX was introduced to prolong the duration of SNB. A double blind, cross-over RCT evaluated the duration of analgesia by LSB with BTX in nine patients with SMP of the lower extremity caused by CRPS. The study reported the median time to analgesia failure was 71 days after LSB with BTA, compared with less than 10 days after standard LSB. They concluded that BTA profoundly prolonged the analgesia from SNB in this pilot study. An effective and durable sympathetic blockade with the mixture of local anesthetics and BTX was reported again in a small case report of LSB on two patients with CRPS in the lower extremity. Pain intensity and the neuropathic symptoms and signs score were significantly reduced, allodynia and coldness disappeared, and skin color returned to normal. In agreement with these observations, another single case report described similar favorable outcomes after a subcutaneous injection of BTX-A in a patient with CRPS in the upper extremity.

Due to the ease of application, the relative safety, and the limitations of alternative treatment options for CRPS, SNB—particularly when used in the context of a comprehensive treatment strategy—is a reasonable treatment option to consider for patients with CRPS refractory to pharmacologic and nonpharmacologic noninterventional treatments, especially when conducted early in the disease course, and when the patient favors such treatment before consideration of more invasive options, such as SCS.

Trigeminal Neuralgia and Trigeminal Neuropathy

Most of the evidence for the efficacy of BTX-A in treating NP comes from trigeminal neuralgia (TN). There are 20 reports (including three double-blind and one single-blind studies ) describing favorable effects and no serious side effects. A 13-week, randomized, parallel design, double-blind, placebo-controlled study assessed the subcutaneous injection of BTX-A in dosages up to 75 U in the trigeminal area affected, and demonstrated significant reduction in pain frequency and intensity. There were a higher number of pain responders in the interventional group (21 subjects) compared to the saline group (19 subjects), with some side effects, such as mild facial asymmetry and local facial swelling. Two years later, the same group of authors compared the effects of low-dose (25 U) and high-dose (75 U) BTX-A to saline in a similar patient population. The study again reported the efficacy of BTX-A, with comparable efficacy between the groups, but fewer side effects in the low-dose group. A third study evaluated 50 U of BTX-A and found marginal improvement at 2 months, but significant improvement in VAS pain scores at 3 months after injection in the interventional group (20 patients) compared to the placebo group (16 patients). The reduction in pain intensity is clinically significant, as highlighted in a single-blind, randomized control study of 20 subjects, which compared subcutaneous injection of 40–60 U of BTX-A with placebo. This study demonstrated a reduction of 6.5 points on the VAS, compared with three points in the placebo group.

Due to the lack of RCTs or prospective cohort studies, there are few systematic reviews based on uncontrolled case series of interventional treatments with local anesthetics in patients with medically refractory TN. Although the evidence is not robust, evidence-based reviews conclude that percutaneous procedures delivering a local anesthetic at the trigeminal ganglion can play a role in the management of selected patients.

Painful Diabetic and Other Peripheral Neuropathies

Recently, three placebo-controlled, blinded studies and a meta-analysis have appeared in the literature supporting the efficacy of BTX-A for metabolic-induced painful peripheral neuropathies like PDN, although there are still no controlled studies assessing its efficacy in drug-induced and chemotherapy-related painful neuropathies. One double-blind, crossover study of 18 patients in which 4 U per site of Botox were injected intradermally into the hyperesthetic and allodynic foot regions reported improvement in pain reduction and sleep quality at 12 weeks. Another study with a similar size and design reported a marked decrease in both tactile perception and mechanical pain in the interventional group at weeks 1, 4, 8, and 12 after treatment compared with baseline. A third controlled trial assessing the safety and efficacy of repeated subcutaneous administration of BTX-A up to 300 U in 66 patients with NP showed a sustained analgesic effect over 24 weeks from the first administration in the interventional group (34 subjects) compared to the placebo group (32 subjects), with pain on injection being the only adverse effect reported. A meta-analysis that included two studies on PDN showed improvement of 1.96 VAS points following treatment with BTX-A, suggesting a correlation between BTX-A and the improvement in pain scores. General comments on the value of therapeutic nerve blocks are shown in Box 78.2 . The results of BTX injections in TN are shown in Table 78.1 . The results of BTX injections in PDN are shown in Table 78.2 .

BOX 78.2

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