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Local Anesthetic Blockade of Peripheral Nerves for Treatment of Neuralgias

Systematic Analysis

Vlassakov, Kamen V., MD; Narang, Sanjeet, MD; Kissin, Igor, MD, PhD

doi: 10.1213/ANE.0b013e31820d9787
Analgesia: Research Reports
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BACKGROUND: Nerve blocks with local anesthetics have been used in the diagnosis and treatment of neuralgias. Usually these blocks were administered in combination with corticosteroids and other drugs that can be effective by themselves. Although lasting benefits from nerve blocks in neuralgias have long been described, definitive evidence is lacking. We had the following objectives in this systematic review: to analyze the evidence behind the practice of peripheral nerve blockade with local anesthetics in patients with neuralgias and radicular pain syndromes; to assess the duration of pain relief after conduction block resolution; and to evaluate the effectiveness of the treatment of these syndromes with a series of blocks.

METHODS: We searched Medline, Embase, narrative reviews, and book chapters. Only articles published in English were collected. The list of 3347 identified articles was reduced to 39 articles that were read entirely, 12 of which met inclusion criteria.

RESULTS: Twelve included articles were analyzed. Each can be classified as a single case report or case series; there were no controlled studies among them. Nine reports assessed a single block outcome; all recorded pain relief beyond the duration of conduction blockade. Those 9 reports represented a total of 69 patients, 30 of whom had complete pain relief and 10 had relief ≥50%. Seven reports with the assessment of continuous pain ≥1 week after a single block reported complete or profound pain relief in 11 of 17 patients. All 3 reports with the assessment of a series of blocks in a large number of patients (total of 270) reported overall positive results.

CONCLUSION: Because all reviewed articles were only single case reports or case series, no reliable conclusion could be drawn concerning the effectiveness of nerve blocks with local anesthetics in neuralgia. However, 2 features of the analyzed reports—the large magnitude of the effect and the high consistency of the reported outcome—indicate that future research efforts are warranted.

Published ahead of print March 3, 2011

From the Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts.

Supported by the Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital.

The authors declare no conflicts of interest.

Reprints will not be available from the authors.

Address correspondence to Igor Kissin, MD, PhD, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115. Address e-mail to kissin@zeus.bwh.harvard.edu.

Accepted December 15, 2010

Published ahead of print March 3, 2011

Nerve blocks with local anesthetics have frequently been used in the diagnosis and treatment of neuralgias.1 Although in many instances the lasting benefits of such nerve blocks have long been described, a definitive conclusion about the practice is lacking. As a result, the widespread application of nerve blocks is not supported by evidence of efficacy. Usually, these blocks were administered in combination with corticosteroids and other drugs2 that have been shown to have salutary effects on their own. For example, corticosteroids can provide relief in neuralgia via at least 2 mechanisms: an antiinflammatory action and the suppression of ectopic discharge in neural membranes.3 At least 3 puzzling phenomena associated with responses to nerve blocks have been described in the literature: (1) pain relief may far outlast the conduction blockade46; (2) block distal to the site of the pain-inducing lesion may stop or alleviate the pain5,7,8; and (3) blocking a peripheral nerve supplying a large part, but not the whole of the region of pain, may provide pain relief in the entire region.7,9 These phenomena can strengthen the therapeutic potential of nerve blocks with local anesthetics in the treatment of neuralgias.

In this review, we had the following 3 objectives: to scrutinize, based on the evidence in the English language, the likelihood of therapeutic effectiveness of peripheral nerve blockade with local anesthetics in neuralgias and radicular pain syndromes well beyond duration of sensory blockade; to assess how long the pain relief persists after a single block; and to evaluate the effectiveness of treating these painful syndromes with a series of blocks.

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METHODS

A comprehensive literature search was conducted using Medline (1966 to March 2010) and Embase (1980 to March 2010), and book chapters. Only articles published in the English language were collected. The list of identified articles was reviewed to find potentially eligible studies.

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Inclusion Criteria

All types of original reports were reviewed, including observational studies, case series, and single case reports evaluating the therapeutic effect of somatic peripheral nerve blocks with local anesthetics on neuralgias or radicular pain syndromes associated with chronic pain of more than a 3-month duration.

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Exclusion Criteria

Interventions excluded were neuraxial blocks, lumbar facet joint interventions (including medial branch block), sympathetic blocks, neurolytic blocks (radiofrequency, thermocoagulation, cryotherapy, and chemical lesions), and local anesthetic skin infiltration. Pain syndromes excluded were migraine, low back pain without radicular pain, complex regional pain syndromes, herpes zoster of less than a 3-month duration, visceral pain, and pain of malignancy. We also excluded observations without assessment of the clinical effect of peripheral nerve blockade beyond the duration of conduction blockade.

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Keywords

According to general pain terms: “Neuralgia,” “Radicular pain,” “Chronic pain,” “Neuropathic pain”; the names of some specific pain syndromes indicated in Merskey and Bogduk10: “Trigeminal neuralgia,” “Geniculate neuralgia,” “Glossopharyngeal neuralgia,” “Occipital neuralgia,” “Brachial plexus neuralgia,” “Segmental peripheral neuralgia,” “Intercostal neuralgia,” “Postherpetic neuralgia,” “Sciatica neuralgia,” “Meralgia paresthetica,” “Femoral neuralgia,” “Obturator neuralgia,” “Iliohypogastric neuralgia,” “Ilioinguinal neuralgia,” and “Genitofemoral neuralgia.” According to specific peripheral nerve blocks: “Trigeminal nerve block,” “Supraorbital nerve block,” “Infraorbital nerve block,” “Mandibular nerve block,” “Maxillary nerve block,” “Occipital nerve block,” “Brachial plexus block,” “Ulnar nerve block,” Spinal nerve block,” “Intercostal nerve block,” “Lumbar dorsal ramus block,” “Lumbar nerve block,” “Sacral nerve block,” “Sciatic nerve block,” “Femoral nerve block,” “Common peroneal nerve block,” “Tibial nerve block,” “Saphenous nerve block,” “Obturator nerve block,” “Ilioinguinal nerve block,” “Iliohypogastric nerve block,” “Pudendal nerve block,” and “Genitofemoral nerve block.” Terms added to the name of a specific neuralgia were “Nerve block” and (“Local anesthetics” or “Bupivacaine,” or “Lidocaine”). Terms added to the name of a specific nerve block were “Neuralgia” or “Chronic pain” or “Neuropathic pain.”

The electronic and manual search of literature identified 3347 articles. The results of this initial search were reduced to 39 articles after reviewing the titles and abstracts. These 39 were read entirely.

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RESULTS

The search identified 39 reports as possibly relevant, 27 of which were excluded after the initial review1136 (Table 1). Most of the reports (18 of 27) were excluded because of the addition of other drugs with possible therapeutic effects in neuralgias: corticosteroids, clonidine, fentanyl, morphine, ketamine, or streptomycin. Seven reports were excluded because there was no assessment of pain relief beyond the period of conduction blockade, and 2 reports were not included because of the use of local anesthetics in concentrations that might have caused a neurolytic blockade.

Table 1

Table 1

All included articles57,3746 (Table 2) can be classified as single case reports or case series; there were no controlled studies. Pain syndromes included various neuralgias (Table 3), the most common of which was sciatic radicular pain. Nerve blocks were usually provided with lidocaine (1% or 2%) or bupivacaine (0.25% or 0.5%). The primary outcome measure in most reports was pain intensity, on either a visual analog scale or a numeric rating scale. It was possible to assess the outcome of a single block in 9 reports, and 3 reports gave the outcome after a series of blocks in a large group of patients.

Table 2

Table 2

Table 3

Table 3

All 9 publications assessing single block outcome described patients with complete pain relief or relief >50% beyond the duration of blockade (Table 3). The total number of patients in all reports with single block assessment was 69, 30 (43%) of whom had complete pain relief beyond the duration of conduction block. In patients with continuous pain (7 reports with the assessment of pain at least 1 week after the block), single block provided pain relief (complete or >50%) lasting a week or longer in 11 of 17 patients (Table 3, including notes on the duration of pain relief).

In 3 of the 5 series of block studies (Table 4), the effects of nerve blocks were studied in relatively large groups of patients. In the Arner et al.6 study (Table 2), 38 consecutive patients with various neuralgias after peripheral nerve injuries (mostly the ilioinguinal or saphenous nerves) received a series of nerve blocks (median 5 blocks) with 0.5% bupivacaine. In 18 patients, analgesia outlasted the conduction block. Sixteen patients experienced improvements with less pain for weeks to months after the series of blocks (up to 23 blocks over several years). Inan et al.40 (Table 2) treated 28 patients with continuous cervicogenic headache (and signs of cervical nerve root involvement) by cervical nerve (C2–3) block (14 patients) or greater occipital nerve block (14 patients). It should be noted that the diagnosis of cervicogenic headache is a subject of controversy.45 Three nerve blocks (1% lidocaine first then 0.25% bupivacaine) were provided at weekly intervals. Two months after the last block, pain intensity continued to be lower, a decrease from 5.8 ± 2.0 (visual analog scale 0 to 10, baseline) to 2.7 ± 2.2 with greater occipital nerve and from 6.8 ± 1.9 to 1.5 ± 1.8 with C2–3 blocks. Sangwan et al.41 (Table 2) treated 210 patients with sciatic radicular pain due to prolapsed intervertebral disks. The patients received 2 or 3 common peroneal blocks with 2% lidocaine, at 1- or 2-week intervals. Pain was assessed 15 days after the last injection. Blocks decreased pain intensity from 3.0 ± 0.5 (a 4-point scale, baseline) to 0.9 ± 0.1. A simultaneously measured straight leg-raising test showed an improvement from 32 ± 13 to 60 ± 12 degrees. The positive effect was observed in 175 of 210 patients within a week after the first block.

Table 4

Table 4

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DISCUSSION

This review demonstrates that there have been no controlled studies on the analgesic effect of nerve blocks in neuralgias. All articles included in the review are single case reports or case series. Only 2 of them (Inan et al.40 and Stajcic et al.43) used randomization and 1 (Arner et al.6) included consecutive patients (Table 2). They represent the lowest of 4 categories of research publications: category characterized by very low quality of evidence. This assessment is attributed to the limitations in design and execution, such as lack of allocation concealment, lack of blinding, lack of accounting, and failure to adhere to intention-to-treat principle.47 However, taken together, these reports have 2 common features important for the assessment of the general quality of evidence: the large magnitude of the effect and the high consistency of the reported outcomes. The magnitude of effect observed in the evaluated reports should be graded as large, because collectively more than half of the patients had pain relief >50%, including complete relief often lasting more than a week after conduction block resolution. If 43% of patients achieve complete pain relief from a single block, the effect would be considered of large magnitude. The consistency of results is also impressive: all 12 articles reported pain relief, and 7 of 9 articles with single block assessment demonstrated pain relief in more than half of patients (Table 3).

One of the aims of this review was to assess how long pain relief persists after a single block. The short-term effect of a single block (e.g., a few days or a week) may not be clinically relevant in chronic pain. However, the data in this regard will have relevance for the treatment of chronic pain if the effect of a single block is lasting long enough to justify a series of blocks at weekly or biweekly intervals if there is a progressive prolongation of pain relief. The assessment was limited by the small number of patients with repeated measurements of pain intensity for a long period after the block. In patients with continuous pain, there were 7 reports with a total of 17 patients; 11 of them (two-thirds) experienced complete or profound pain relief that lasted a week or more. This invites the presumption that a series of nerve blocks with local anesthetics at weekly (or even longer) intervals could be a useful approach in the treatment of neuralgias. Evidence supporting such a presumption is provided in the results of 3 studies6,40,41 that tried this approach; all reported positive results.

The majority of the reviewed publications reported pain relief after nerve blocks performed distal to the site of the pain-inducing lesion. This phenomenon was described not only in the studies on pain relief after the resolution of conduction block,5,7,41 but also in studies excluded from this review because they assessed pain relief only during conduction block.8,9,35 This phenomenon in principle could be partly explained by the central action of the local anesthetic after systemic absorption from the site of the block. The central action of local anesthetics in neuropathic pain is well known.4850 The central effect is especially likely when local anesthetics are used at high doses. However, in many blocks used for neuralgias, the injected volumes are rather small. In addition, control experiments with injections of local anesthetic beyond the site of the block did not provide pain relief despite use of the same dose.5 At the same time, complete and long-lasting pain relief in the leg was not accompanied by a similar effect on low back pain, i.e., there was no effect outside the distribution of the sciatic nerve.5,7

Another explanation for the pain relief elicited by the block distal to the site of the pain-inducing lesion is the proximal spread of the injected anesthetic providing local antiinflammatory action at the site of the lesion. This would be especially likely when the site of injection is particularly close to the area of nerve damage. It is difficult to explain significant benefits secondary to proximal spread from small nerves such as the occipital and saphenous nerves. In some reports,9 the effect was observed despite a long distance between the site of nerve block (ankle) and the area of complete radicular pain relief (thigh). The effect due to proximal spread of local anesthetics along the nerve is possible but unlikely.6,51

Block of the peripheral nerve can provide pain relief in a region much larger than that supplied by the blocked nerve. This was most obvious after blockade of sciatic nerve branches.9 Blocks of the common peroneal nerve or tibial nerve even as distally as at the ankle can produce pain relief throughout the distribution of the sciatic nerve, well above the level of the block. That was probably how the common peroneal nerve block41 or, surprisingly, saphenous nerve block7 provided relief of sciatic radicular pain beyond the innervation area of the blocked nerve and in the entire lower limb.

The most promising feature associated with the prospective use of nerve blocks in the treatment of neuralgias is that pain relief far outlasts the conduction blockade. To explain the long-lasting effects of nerve blocks in chronic pain, Livingston4 hypothesized long ago the possibility of interruption of the “vicious cycle” of self-sustaining pain. A more recent suggestion for the explanation of the long-lasting pain-relieving effect of nerve blocks in neuropathic pain involves elimination of central sensitization maintenance.52 Whatever the exact mechanism, it remains very difficult to explain why pain relief after the recovery from conduction anesthesia varies from several hours to several months. If the results presented above are indeed accurate, it is possible to expect that nerve blocks could provide a reasonable treatment alternative in approximately half of the patients with neuralgias. In addition, these pain-relieving effects beyond the expected anatomical boundaries and/or the duration of anesthetic action might put into question the diagnostic role of peripheral nerve blockade.

This systematic review is subject to certain limitations. Publication bias cannot be excluded: trial results were not published because of their negative nature.53 As a result, the potential to skew positive effect was present. In addition, unsystematic clinical observations presented in this review are characterized by very low quality of evidence. Therefore, the calculations of the outcomes cannot provide a reliable conclusion concerning the effectiveness of local anesthetic blocks in neuralgias. Two features of the analyzed reports, the large magnitude of effects and the high consistency of the reported outcomes, indicate that future research efforts are warranted. Thus, our analysis reveals discrepancy between mostly positive results published in the literature and very low quality of evidence in the studies presenting these results.

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DISCLOSURES

Name: Kamen V. Vlassakov, MD.

Contribution: This author analyzed the data and write the manuscript.

Attestation: Kamen V. Vlassakov has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Name: Sanjeet Narang, MD.

Contribution: This author helped analyze the data and write the manuscript.

Attestation: Sanjeet Narang has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Name: Igor Kissin, MD, PhD.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Attestation: Igor Kissin has seen the original study data, reviewed the analysis of the data, approved the final manuscript, and is the author responsible for archiving the study files.

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