Psychosocial Factors Predict Analgesic Response to Morphine

endogenous opioid system
endogenous opioid system
Psychosocial variables such as depression and anxiety predict the response to morphine analgesia in patients with low back pain.

A study published in the March 2017 issue of Pain showed that psychosocial variables such as depression and anxiety predict the response to morphine analgesia in patients with low back pain (LBP), and that endogenous opioid (EO) function at least partially mediates this link.1

Despite the common use of opioid analgesics in the management of chronic pain, no factors have been identified that could predict optimal efficacy of these agents. Earlier findings have demonstrated increased postoperative analgesic requirements in patients with greater negative emotional affect, suggesting a lower analgesic response in those individuals.2,3 In placebo-controlled research involving experimentally induced pain, increased negative affect predicted a lower response to opioid analgesia.4

Citing the need for more well-controlled studies to investigate these links and identify additional psychosocial factors, the authors of the current study examined potential predictors of opioid-related improvement in LBP. The researchers examined whether mechanisms underlying this association are mediated by EO function. In a previous study, participants who were treated with naloxone (8 mg) to block endogenous opioid signaling displayed higher levels of anger.5 Other results showed lower opioid analgesia, as well as increased pain responsiveness in patients with greater EO function.6

The researchers compared the intensity of LBP in 89 patients before and after they received either a placebo or intravenous naloxone or morphine. The conditions were administered in a counterbalanced manner across 3 sessions. Pain was assessed with the McGill Pain Questionnaire-Short Form, and multiple validated instruments were used to assess psychosocial factors, including the Trait Anger Scale, the Beck Depression Inventory, the State-Trait Anxiety Inventory, the Pain Catastrophizing Scale, and the Pain Disability Index.

The findings demonstrate a significant and positive relationship between morphine analgesic response and most psychosocial factors, whereas negative associations were found between EO function and scores on the Beck Depression Inventory, State-Trait Anxiety Inventory, Pain Catastrophizing Scale, and Pain Disability Index. Further analysis revealed that EO function partially mediated the relationship between these 4 variables and morphine analgesic response.

“Results suggest that psychosocial factors predict elevated analgesic responses to opioid-based medications, and may serve as markers to identify individuals who benefit most from opioid therapy,” the authors wrote. These observations “may guide future work on finding markers for optimal opioid therapy in chronic pain patients undergoing daily opioid treatment,” they concluded.

Summary & Clinical Applicability

These findings show that several psychosocial factors predict analgesic response to morphine, and that this link is at least partially mediated by endogenous opioid function.


The generalizability of the current research is limited, as none of the participants were taking daily opioid analgesics, and only a single opioid analgesic was tested with a single dose.

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  1. Burns JW, Bruehl S, France CR, et al. Psychosocial factors predict opioid analgesia through endogenous opioid function. Pain. 2017;158(3):391-399. doi: 10.1097/j.pain.000000000000076
  2. De Cosmo G, Congedo E, Lai C, Primieri P, Dottarelli A, Aceto P. Preoperative psychologic and demographic predictors of pain perception and tramadol consumption using intravenous patient controlled analgesia. Clin J Pain. 2008; 24(5):399-405. doi: 10.1097/AJP.0b013e3181671a08
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  4. Geha H, Nimeskern N, Beziat JL. Patient-controlled analgesia in orthognathic surgery: evaluation of the relationship to anxiety and anxiolytics. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;108(3):e33-e36. doi: 10.1016/j.tripleo.2009.05.027
  5. Bruehl S, Burns JW, Chung OY, Quartana P. Anger management style and emotional reactivity to noxious stimuli among chronic pain patients and healthy controls: the role of endogenous opioids. Health Psychol. 2008;27:204-214. doi: 10.1037/0278-6133.27.2.204