Background: Evidence for opioid-induced hyperalgesia (OIH) has been shown in animal and
human studies, but the clinical implications of this phenomenon remain unclear.
Objectives: We examined whether cancer patients taking opioids differ in their sensitivity to a
clinical pain stimulus using a local anesthetic injection compared to those not taking opioids. We
also evaluated the effect of the opioid dose, duration of opioid therapy, and patients’ pain severity
and functional status on this clinical pain stimulus.
Study Design: Prospective observational study.
Setting: University outpatient department for interventional pain management, Republic of
Korea.
Methods: Eighty-two cancer patients including 20 patients not taking opioids (non-opioid group)
and 62 taking opioids (opioid group) who were scheduled for an interventional procedure were
enrolled in this study. Patients received a standardized subcutaneous injection of lidocaine prior
to a full dose of local anesthetic (LA). Before the injection, patients completed the Brief Pain
Inventory (BPI) questionnaire and were asked to rate their current pain using numeric rating scales.
Immediately following the injection, LA injection-specific pain was evaluated using pain intensity,
unpleasantness, and behavior pain scores.
Results: LA injection-specific pain intensity, unpleasantness, and behavior pain score were
significantly higher in the opioid group compared with the non-opioid group (P < 0.001). In the
opioid group, these post-injection pain scores were higher in patients taking high-dose opioids
than those taking low doses (P < 0.05). In addition, we observed a strong correlation between the
baseline BPI pain interference score and the LA injection-specific pain score (r = 0.695, P < 0.001).
Limitations: This study is limited by its sample size and observational design. Various opioid
medications, which were not standardized, may have inadvertently biased our results. Finally, the
pain assessed by a brief stimulus does not fully reflect disturbances in endogenous pain inhibitory
processes.
Conclusion: The results of this study suggest that opioid medication is an important contributing
factor to pain perception accompanying LA injection, and cancer patients using high-dose opioids
may be highly susceptible to hyperalgesic responses to this clinical stimulus. We also suggest that
the possible presence of OIH may be intensified among cancer patients with poor physical and
psychosocial functional status.
Key words: Adverse effects; analgesics, opioid; anesthetics, local; cancer; hyperalgesia; injections,
subcutaneous; nociceptive pain; pain measurement; pain perception; quality of life
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