Psychosocial Factors That May Predict Opioid Analgesia

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Multiple psychosocial factors such as depression, anxiety, and pain catastrophizing are associated with opioid analgesic response.
Multiple psychosocial factors such as depression, anxiety, and pain catastrophizing are associated with opioid analgesic response.

Despite the significant increase in the use of opioid analgesics for chronic pain treatment, variables that may predict their efficacy for a given patient have not yet been elucidated. New research published online in Pain investigated whether psychosocial factors would predict participants' response to opioid analgesics administered for low back pain, and whether this response would be mediated by endogenous opioid (EO) function.1 

In earlier placebo-controlled studies, negative emotional affect (NA) was found to predict lower responses to opioid analgesia administered for experimentally induced pain, and other findings suggest that patients with higher NA may require increased opioid analgesia following surgery than patients with lower NA.2,3 

The authors of the current research noted the need for further studies on these and other psychosocial factors that may influence analgesic response, as well as underlying mechanisms. One possible mechanism is EO function, as indicated by the authors' previous findings linking greater EO function with pain responsiveness and less morphine analgesia.4

In the present investigation, the researchers used an expanded dataset from their prior study to examine these associations in 89 adults with chronic low back pain. Inclusion criteria included chronic daily low back pain for a period of at least 3 months and an average past-month pain intensity of at least 3 on a scale of 1 to 10. Individuals were excluded if they were taking opioids daily or anti-hypertensive drugs, and if they had certain comorbidities such as cardiovascular disease, diabetes, and certain psychiatric disorders.

Across 3 sessions spaced 1 week apart, participants were administered either an opioid analgesic (morphine), an opioid antagonist (naloxone), or a saline placebo in a double-blind, randomized, and counterbalanced manner. The McGill Pain Questionnaire-Short Form (MPQ) was used to assess sensory and affective pain intensity before and after each session, and participants rated the degree to which they were experiencing specific negative emotions before each session.

In addition, emotional tendencies and depression were measured with various tools such as the Trait Anger Scale (TAS), the State-Trait Anxiety Inventory (TAI), and the Beck Depression Inventory (BDI). Participants also completed the Pain Catastrophizing Scale (PCS) and the Pain Disability Index (PDI).

The results show a significant association between each of the psychosocial variables and morphine analgesic response: Higher scores on the BDI, TAI, TAS, PCS, and PDI were linked with a greater analgesic response to morphine, while higher positive affect scores were linked with a lower response. Additionally, higher scores on the BDI, PCS, and PDI were associated with lower EO function, and the “EO function variables for all 3 chronic pain indexes were related significantly to the corresponding morphine analgesic response variables in directions,” linking less EO function with increased analgesic response to morphine (r's = .42 to .77; p's < .01), the authors reported. Bootstrapped mediation analyses revealed that EO function partially mediated the relationships between psychosocial factors and analgesic responses.

These findings “imply that chronic pain patients with elevated levels of negative psychosocial factors may derive more analgesic benefit from opioid therapy for chronic pain than patients with low levels of negative psychosocial factors,” wrote the authors. “Because the former exhibit relatively poor EO function, achieving optimal analgesia may be facilitated by augmentation with exogenous opioids,” and non-pharmacological approaches such as acupuncture and relaxation training may provide additional analgesic benefits and improve EO function.

Summary and Clinical Applicability

New findings reveal that multiple psychosocial factors such as depression, anxiety, and pain catastrophizing are associated with opioid analgesic response, and that this relationship is partially mediated by endogenous opioid function.

Limitations and Disclosures

Limitations: The sample is not representative of typical chronic pain patients in that participants were not taking opioid analgesics daily, and it is also unknown whether similar effects would be observed for other opioid analgesics, as only one was tested in the current study.

Disclosures: The authors declare that they have no conflicts of interest.

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  1. Burns JW, Bruehl S, France CR, et al. Psychosocial factors predict opioid analgesia via endogenous opioid function. Pain. 2016; DOI: 10.1097/j.pain.0000000000000768
  2. Burns JW, Bruehl S, Chung OY, et al. Endogenous opioids may buffer effects of anger arousal on sensitivity to subsequent pain. Pain. 2009; 146: 276-282.
  3. 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: 399-405.
  4. Bruehl S, Burns JW, Gupta R, et al. Endogenous opioid function mediates the association between laboratory evoked pain sensitivity and morphine analgesic responses. Pain. 2013; 154:1856-1864.


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