Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 2 (6), e624

Complex Regional Pain Syndrome-Up-To-Date


Complex Regional Pain Syndrome-Up-To-Date

Frank Birklein et al. Pain Rep.


Complex regional pain syndrome (CRPS) was described for the first time in the 19th century by Silas Weir Mitchell. After the exclusion of other causes, CRPS is characterised by a typical clinical constellation of pain, sensory, autonomic, motor, or trophic symptoms which can no longer be explained by the initial trauma. These symptoms spread distally and are not limited to innervation territories. If CRPS is not improved in the acute phase and becomes chronic, the visible symptoms change throughout because of the changing pathophysiology; the pain, however, remains. The diagnosis is primarily clinical, although in complex cases further technical examination mainly for exclusion of alternative diagnoses is warranted. In the initial phase, the pathophysiology is dominated by a posttraumatic inflammatory reaction by the activation of the innate and adaptive immune system. In particular, without adequate treatment, central nociceptive sensitization, reorganisation, and implicit learning processes develop, whereas the inflammation moderates. The main symptoms then include movement disorders, alternating skin temperature, sensory loss, hyperalgesia, and body perception disturbances. Psychological factors such as posttraumatic stress or pain-related fear may impact the course and the treatability of CRPS. The treatment should be ideally adjusted to the pathophysiology. Pharmacological treatment maybe particularly effective in acute stages and includes steroids, bisphosphonates, and dimethylsulfoxide cream. Common anti-neuropathic pain drugs can be recommended empirically. Intravenous long-term ketamine administration has shown efficacy in randomised controlled trials, but its repeated application is demanding and has side effects. Important components of the treatment include physio- and occupational therapy including behavioural therapy (eg, graded exposure in vivo and graded motor imaging). If psychosocial comorbidities exist, patients should be appropriately treated and supported. Invasive methods should only be used in specialised centres and in carefully evaluated cases. Considering these fundamentals, CRPS often remains a chronic pain disorder but the devastating cases should become rare.

Keywords: Central reorganisation; Complex regional pain syndrome; Neuroplasticity; Posttraumatic inflammation; Treatment.

Conflict of interest statement

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.


Figure 1.
Figure 1.
CRPS-related fixed dystonia (A) before and (B) after botulinum toxin A treatment. Pain improves in parallel with a reduction in muscle contraction. CRPS, complex regional pain syndrome.
Figure 2.
Figure 2.
The authors' suggestion of a resource-effective treatment algorithm for CRPS (details see text). Under the assumption that meta-analyses request “better or more RCTs” for any CRPS therapy, we suggest a stepwise approach starting with noninvasive treatment with proportionate risks (“nihil nocere”). Nonpharmacological treatment is intensive but not too time consuming at the beginning. Evaluation of psychological factors, which prevent improvement, follows early, and nonpharmacological treatment becomes more intense. Invasive treatment should be performed only by specialists; minimally invasive procedures should be tried before implantation of neuroprosthetics. BoNT/A, botulinum toxin type A; CRPS, complex regional pain syndrome; DMSO, dimethylsulfoxide; DRG, dorsal root ganglion, (stimulation); GEXP, graded exposure in vivo; i.m., intramuscular; i.v., intravenous; SCS, spinal cord stimulation.

Similar articles

See all similar articles

Cited by 4 PubMed Central articles


    1. Allen G, Galer BS, Schwartz L. Epidemiology of complex regional pain syndrome: a retrospective chart review of 134 patients. PAIN 1999;80:539–44. - PubMed
    1. Arnold JMO, Teasell RW, MacLeod AP, Brown JE, Carruthers SG. Increased venous alpha-adrenoreceptor responsiveness in patients with reflex sympathetic dystrophy. Ann Int Med 1993;118:619–21. - PubMed
    1. Barnhoorn KJ, van de Meent H, van Dongen RT, Klomp FP, Groenewoud H, Samwel H, Nijhuis-van der Sanden MW, Frolke JP, Staal JB. Pain exposure physical therapy (PEPT) compared to conventional treatment in complex regional pain syndrome type 1: a randomised controlled trial. BMJ Open 2015;5:e008283. - PMC - PubMed
    1. Baron R, Schattschneider J, Binder A, Siebrecht D, Wasner G. Relation between sympathetic vasoconstrictor activity and pain and hyperalgesia in complex regional pain syndromes: a case-control study. Lancet 2002;359:1655–60. - PubMed
    1. Bean DJ, Johnson MH, Heiss-Dunlop W, Kydd RR. Extent of recovery in the first 12 months of complex regional pain syndrome type-1: a prospective study. Eur J Pain 2016;20:884–94. - PubMed

LinkOut - more resources