Chronic Opioid Use in Fibromyalgia Syndrome

A Clinical Review

Jacob T. Painter, PharmD, MBA, PhD; Leslie J. Crofford, MD


J Clin Rheumatol. 2013;19(2):72-77. 

In This Article

Concerns Regarding Opioid Use in FM

Opioid use in chronic nonmalignant pain is a divisive subject in the current literature. Current guidelines suggest guarded use of opioids chronically in nonmalignant pain, and these recommendations are based on moderate quality evidence at best.[48] Despite these recommendations, the use of chronic opioid therapy for the control of nonmalignant pain has increased tremendously over the past decade.[48] Between 2005 and 2009, the rate of emergency department visits due to misuse or abuse of oxycodone products increased by 242.2%, the leading agent in a problem that spans the entire opioid class; morphine, hydrocodone, and fentanyl products all more than doubled in their rates of emergency department visits over the period.[48] In 2007, misuse or abuse of pharmaceuticals surpassed illicit drugs becoming the second leading cause of drug-related emergency department visit.[49]

In addition to the immense societal concerns posed by increased opioid utilization, there are the individual adverse effects seen in patients treated with these medications. Common complications due to opioid administration include constipation, pruritus, respiratory depression, nausea, vomiting, delayed gastric emptying, sexual dysfunction, muscle rigidity and myoclonus, sleep disturbance, pyrexia, diminished psychomotor performance, cognitive impairment, dizziness, and sedation[50] (Table 3). Beyond the effects seen with short-term administration, another set of adverse effects is seen with administration of opioids for the treatment of chronic pain. Long-term utilization of opioids is associated with hormonal and immune dysfunction, abuse and addiction, tolerance, and hyperalgesia.[51]

Opioid-induced hyperalgesia manifests as reduced nociceptive threshold and is primarily thought to be the result of central sensitization of pronociceptive pathways.[7] Opioid-induced hyperalgesia presents as heightened atypical pain sensations distinct from the original pain stimulus, with a separate location and altered distribution from the original complaint.[52] Opioid-induced hyperalgesia can be recognized clinically as persistent or increasing pain with increasing dose, pain worse on opioids than before, decreasing duration of analgesic effect, and pain becoming increasingly diffuse or poorly localized with ongoing opioid use. Both tolerance and opioid-induced hyperalgesia are concerns with any chronic pain condition; however, because of the pathophysiologic characteristics seen in FM, the use of opioids chronically in these patients deserves extra scrutiny. FM is a syndrome of central pain amplification that could be facilitated or augmented by opioid effects. Specifically, opioids are known to affect the activation state of spinal glia that supports a state of activation of pain transmission neurons.[12] There is reason to suspect that this property of opioids is particularly detrimental to FM and related disorders characterized by chronic neuronal activation.

Patients with FM may also have altered endogenous opioid activity that further complicates the evaluation of the utility of these drugs. A study utilizing positron emission tomography found that patients with FM exhibit decreased μ-opioid receptor availability in areas of the brain key to pain and nociception processing.[53] There are 2 possible explanations for the demonstrated reduced availability. First, endogenous enkephalin levels are elevated in patients with FM, even when compared with patients with chronic low-back pain.[54] Elevated endogenous ligands in these patients may explain the reduced availability of receptors to opioids, decreasing their effectiveness in FM patients. Another possible explanation is that the increased presence of endogenous ligands may lead to down-regulation of opioid receptors.

Not only is the failure rate of opioid use a greater concern in patients with FM, but there is also an increased concern of misuse or abuse among this population because of characteristics commonly seen in these patients. Risk factors commonly associated with nonmedical use of opioids include anxiety and mood disorders, each a common comorbidity seen in patients with FM.[55] Furthermore, low self-rated health status, commonly seen in FM, increases the propensity toward misuse or abuse of opioids.[55] In addition to these concerns, many other consequences of opioid use are already concerns that both patients and practitioners are aware of in FM patients; these include cognitive difficulties, decreased motivation to pursue nonpharmacologic treatment modalities, increased propensity for depression, and a negative stigma within the health care system.[56]

Beyond these reasons, there is also increased concern of adverse effect presentation in patients with FM. FM patients report adverse effects and intolerance to treatment at elevated rates.[57] In addition to the increased reporting of adverse effects in general, specific adverse effects seen with opioid use may affect FM patients disproportionately. Although opioids may temporarily control the pain experienced in the disorder, their use may significantly complicate other aspects of the syndrome including nonrestorative sleep, fatigue, and irritable bowel. Constipation is a hallmark effect seen with opioid use and may be of increased concern in patients with the irritable bowel symptoms commonly associated with FM. Other adverse effects such as sedation and mental clouding are also of particular concern in patients with FM because of the possible preexisting presence of these problems due to the syndrome. Finally, opioid-induced effects on sleep, such as sleep-disordered breathing, may further exacerbate unrefreshed sleep and fatigue.[58]