PAIN 155 (2014) 22182219

www.elsevier.com/locate/pain

Commentary

Sympathetic blockade for complex regional pain syndrome

In the 1990s, the dogma that sympathetic blockade was a rstline treatment for complex regional pain syndrome (CRPS) was
shattered by accusations that benets were due to placebo effects
and that this treatment approach was entrepreneurially inspired
[7]. Since then, systematic examination of the literature base has
provided little support for the use of local anesthetic sympathetic
blockade for CRPS, and has highlighted the scarcity of high-quality
double-blind placebo-controlled trials with an adequate sample
size and follow-up period [1,9]. However, as sympathetic blockade
continues to be used therapeutically for CRPS in clinical practice
[10], further examination of its efcacy is imperative.
In this issue of PAIN, Rocha et al. [8] report that thoracic sympathetic blockade, as an adjunct to pharmacological and physical
therapy for patients with upper-limb CRPS, resulted in positive
effects on mood and reductions in pain detectable 12 months later.
During the blockade, 1 mL of contrast media, followed by 5 mL of
local anesthetic agent and another 5 mL of corticosteroid solution,
were injected under uoroscopic guidance around the second thoracic ganglion of the sympathetic chain. In the control group, 10 mL
of local anesthetic agent and corticosteroid solution were injected
subcutaneously at the T2 level to cover the possibility that placebo
effects or systemic absorption of these agents might provide therapeutic benets. Scores on the McGill Pain Questionnaire and the
average evoked pain score on the Neuropathic Pain Symptom
Inventory were signicantly lower in the treated than control group
at 1 and 12 months, and average pain and depression scores were
signicantly lower in the treated than control group at 12 months.
What might account for such persistent treatment gains after
just one sympathetic block? It seems quite unlikely that a placebo
response to sympathetic blockade would be detected 12 months
later. Substantial increases in hand temperature indicated that
sympathetic blockade was successful. However, patients apparently remained blind to the type of treatment they received,
despite the increase in hand temperature and the occasional
presence of Horners sign. Although a case might be made for
temporary treatment gains in patients with a component of
sympathetically maintained pain [3], it seems inconceivable that
transient blockade of ganglia in the thoracic sympathetic chain
would inhibit pain and lift mood 12 months later.
Might the infusion of corticosteroid solution around the sympathetic chain have mediated long-term benets? Adding steroids to
local anesthetic agents for sympathetic nerve blocks is based on the
premise that suppressing inammation in the sympathetic chain

inhibits pain. There is some support for this. For example, when
administered repetitively over the course of a week to the sympathetic chain with local anesthetic agent, steroids seemed to provide
therapeutic benets for patients with acute herpes zoster and
reduced the rate of progression to postherpetic neuralgia [4].
However, one might question whether the sympathetic chain
was the only target of the local anesthetic agent and corticosteroid
solution in Rochas study, because contrast media in 11 mL of uid
(the volume injected by Rocha et al.) can disperse a considerable
distance from the site of injection. For example, local anesthetic
agent in volumes as low as 2 mL spreads across approximately 5
spinal segments and produces physiological signs of sympathetic
blockade [5]. In an animal model of low back pain, steroids applied
locally to inamed dorsal root ganglia inhibited mechanical sensitivity and reduced abnormal spontaneous activity in myelinated
sensory neurons [11]. Furthermore, after spinal nerve ligation in
rats, corticosteroids infused around the involved dorsal root ganglia inhibited mechanical sensitivity and sympathetic sprouting
into the ganglia [6]. Potentially, then, absorption of the corticosteroid solution into nearby dorsal root ganglia of patients in Rochas
study might have contributed to treatment gains. Perhaps this or
some other effect of the steroids, local anesthetic agent, or blocking
procedure augmented the efcacy of physical treatments or pharmacotherapy, resulting in progressive reductions in pain and positive effects on mood over the 12 months of follow-up.
Although this study casts little light on the role, if any, of local
anesthetic sympathetic blockade in the management of CRPS, therapeutic effects were promising and warrant further investigation.
And we should not lose sight of the bigger picture. A clear
distinction needs to be made between the use of sympathetic
nerve blocks to identify sympathetically maintained pain (when
compared against an active placebo procedure) and the therapeutic
application of sympathetic blockade for CRPS. Indeed, we may be
asking the wrong question by querying the therapeutic role of local
anesthetic sympathetic blockade for CRPS [1,9]it would seem
more pertinent to determine whether and how to interrupt sympathetic activity in patients with sympathetically maintained CRPS
rather than in CRPS patients overall. To avoid a tautology, new
approaches may be required to identify sympathetically maintained pain (eg, placebo-controlled electrical or pharmacological
stimulation of the sympathetic chain or sympathetic nerve terminals), and to distinguish between central and peripheral forms of
this disorder [2]. We might then be better placed to determine
whether therapies that target the sympathetic nervous system
provide benets for an identiable subgroup of patients with CRPS.

DOI of original article: http://dx.doi.org/10.1016/j.pain.2014.08.015

http://dx.doi.org/10.1016/j.pain.2014.09.005
0304-3959/ 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Commentary / PAIN 155 (2014) 22182219

Conict of interest
The authors declare no conict of interest.
Acknowledgements
Supported by grants from the National Health and Medical
Research Council of Australia (grant APP1030379) and the Australian and New Zealand College of Anaesthetists (grant 12/24).
References
[1] Cepeda MS, Carr DB, Lau J. Local anesthetic sympathetic blockade for complex
regional pain syndrome. Cochrane Database Syst Rev 2005;4:CD004598.
[2] Drummond PD, Finch PM. Persistence of pain induced by startle and forehead
cooling after sympathetic blockade in patients with complex regional pain
syndrome. J Neurol Neurosurg Psychiatry 2004;75:98102.
[3] Gibbs GF, Drummond PD, Finch PM, Phillips JK. Unravelling the
pathophysiology of complex regional pain syndrome: focus on
sympathetically maintained pain. Clin Exp Pharmacol Physiol 2008;35:71724.
[4] Ji G, Niu J, Shi Y, Hou L, Lu Y, Xiong L. The effectiveness of repetitive
paravertebral injections with local anesthetics and steroids for the prevention
of postherpetic neuralgia in patients with acute herpes zoster. Anesth Analg
2009;109:16515.
[5] Lee MH, Kim KY, Song JH, Jung HJ, Lim HK, Lee DI, Cha YD. Minimal volume of
local anesthetic required for an ultrasound-guided SGB. Pain Med 2012;13:
13818.

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[6] Li JY, Xie W, Strong JA, Guo QL, Zhang JM. Mechanical hypersensitivity,
sympathetic sprouting, and glial activation are attenuated by local injection of
corticosteroid near the lumbar ganglion in a rat model of neuropathic pain. Reg
Anesth Pain Med 2011;36:5662.
[7] Ochoa JL. Truths, errors, and lies around reex sympathetic dystrophy and
complex regional pain syndrome. J Neurol 1999;246:8759.
[8] Rocha RO, Teixeira MJ, Yeng LT, Cantara MG, Faria VG, Liggieri V, Loduce A,
Mller BM, Souza ACMS, de Andrade DC. Thoracic sympathetic block for the
treatment of complex regional pain syndrome type I: A double-blind
randomized controlled study. PAIN 2014;155:227481.
[9] Stanton TR, Wand BM, Carr DB, Birklein F, Wasner GL, OConnell NE. Local
anaesthetic sympathetic blockade for complex regional pain syndrome.
Cochrane Database Syst Rev 2013;8:CD004598.
[10] van Eijs F, Geurts J, van Kleef M, Faber CG, Perez RS, Kessels AG, van Zundert J.
Predictors of pain relieving response to sympathetic blockade in complex
regional pain syndrome type 1. Anesthesiology 2012;116:11321.
[11] Ye L, Xie W, Strong JA, Zhang JM. Blocking the mineralocorticoid receptor
improves effectiveness of steroid treatment for low back pain in rats.
Anesthesiology 2014;121:63243.

Peter D. Drummond
Philip M. Finch
Centre for Research on Chronic Pain and Inammatory Diseases, and the
School of Psychology and Exercise Science, Murdoch University,
Perth 6150, Australia
Tel.: +61 893602415; Fax: +61 893606492.
E-mail address: P.Drummond@murdoch.edu.au (P.D. Drummond)