Opioids: Friend or Foe? | CRPS

Published on September 6, 2016 under Guest Blogger for RSDSA

Opioids are they friend or foe to people living with CRPS?By Alaa A. Abd-Elsayed, MD (Dr. Al)

Assistant Professor Department of Anesthesiology

University of Wisconsin School of Medicine and Public Health

Madison, WI


It is nearly impossible to search for information on chronic pain conditions without stumbling across articles on the dangers of opioids.  The FDA has recently published action plans to reduce opioid abuse and a number of states are putting together new regulations regarding opioid prescribing.  For those suffering with chronic pain, all this negative talk of opioids can make someone who is using (not abusing) them feel like they are wearing a scarlet letter.  While the rationale for implementing these strict regulations on opioid prescriptions comes with good intent, it is also a burden those in need of adequate pain relief.

What many people forget is that opioids are not FDA approved for the treatment of chronic pain (greater than 3 months) – which is why, in part, regulators are beginning to crack down on long term opioid use.  So, the question remains – for those suffering with chronic pain, are opioids really the right choice?

When exploring treatment options for CRPS, the usual suspects are always noted: NSAIDs, neuropathic pain meds (gabapentin, pregabalin), antidepressants (amitriptyline, duloxetine), opioids, topical pain relief, physical therapy, and sympathetic nerve blocks.  Although these medications are widely used, none of these agents have been approved by the FDA for the treatment of CRPS – and there is limited efficacy data to support their use.  Specific to opioids, only one randomized controlled trial in patients with CRPS has been studied.  This study found no difference in pain relief between morphine and placebo (Harke, 2001).  Although the data is limited, the US CRPS treatment guidelines (Harden, 2013) still state that while opioids are a reasonable second- or third-line treatment option to try, they should not be used initially.

Since opioids really aren’t a good option for initial treatment of CRPS, what could be?  Results of several small trials reported over the last 15+ years suggest that bisphosphonates should be explored for early CRPS-1.  Bisphosphonates are a class of medications used to treat osteoporosis and other bone-related conditions.  The benefits of bisphosphonates is that they are non-opioid and may reduce pain by targeting one of the key mechanisms in early CRPS (localized osteoporosis at the site of injury).  Five placebo-controlled trials with various bisphosphonates have been completed, and each one of these studies saw statistically significant improvements in pain scores (Adami, 1997; Varenna, 2000; Robinson, 2013; Manicourt, 2004; Varenna, 2013).  The fact that these studies were generally small in size and conducted at single centers makes it hard to draw definitive conclusions. But taken together the results support the study of this class of drugs for the treatment of early CRPS-1.

Currently, no bisphosphonates are approved for the treatment of CRPS, however, there is a large, multi-national, ongoing clinical trial evaluating the use of oral zoledronic acid (AXS-02) in patients with early CRPS-1.  This study marks the first oral bisphosphonate to be evaluated for CRPS in a large clinical study with the intent of gaining FDA approval.  To learn more about this study visit www.CRPStrial.com, additional information about this study and other ongoing clinical trials can be searched for on www.clinicaltrials.gov.


Dr. Al is a pain medicine physician at the University of Wisconsin Pain Clinic who regularly treats patients with CRPS.  Dr. Al is an investigator in the CREATE-1 study and is actively recruiting patients, contact his research coordinator if you are interested in learning more about the study (Maggie Chilsen, mchilsen@wisc.edu).  




Harke H, et al. Anesth Analg. 2001; 92:488–495

Harden RN, et al. Pain Med. 2013 Feb;14(2):180-229.

Adami S. et al. Ann Rheum Dis. 1997;56:201-204.

Varenna M. et al. J Rheumatol. 2000;27:1477-1483.

Robinson JN, et al. Pain Med. 2004;5:276-280.

Manicourt DH, et al. Arthritis Rheum. 2004;50:3690-3697.

Varenna M. et al. Rheumatology (Oxford). 2013;52:534-542.


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