Opioid responsiveness of nociceptive versus mixed pain in clinical cancer patients

Published:November 12, 2018DOI:


      • Cancer pain driven by neuropathic mechanisms is believed to be opioid resistant.
      • We find similar opioid requirements in nociceptive and mixed cancer pain patients.
      • Mixed cancer pain may be considered a type of nociceptive pain.



      To investigate whether clinical cancer patients with mixed nociceptive–neuropathic pain are less responsive to opioids than patients with nociceptive pain.


      Pain is common in advanced cancer patients. Pain driven by neuropathic mechanisms is considered to be resistant to opioids. This hypothesis is mainly based on animal studies and single-dose opioid studies in humans but has not been confirmed in clinical practice.


      Data were prospectively collected from 240 clinical cancer pain patients using opioids. Multiple linear regression was used for assessing the associations between the logarithm of the morphine equivalent dose (MED) at three days after admission (T = 3d) relative to admission (T = 0d) (logRMED) and type of pain (nociceptive versus mixed pain), corrected for gender, age, primary cancer site and use of non-opioid and adjuvant analgesics. As secondary outcome measures, associations between logMED and logPFent (fentanyl plasma level) at T = 3d and type of pain were assessed.


      Pain intensity between T = 0d and T = 3d was significantly and evenly reduced in patients with nociceptive pain (n = 173) and mixed pain (n = 67). Median (interquartile range) MED was 20 (10–52) and 20 (20–80) mg (T = 0d), 40 (10–67) and 40 (20–100) mg (T = 3d), median PFent (T = 3d) was 1.59 (0.58–3.19) and 1.38 (0.54–4.39) ng/ml, none of them significantly different, in patients with nociceptive and mixed pain, respectively. Neither logRMED, logMED (T = 3d), or logPFent (T = 3d) was significantly associated with type of pain, after correction for confounding factors.


      We conclude that, at least in clinical cancer patients, mixed pain is as responsive to opioids as nociceptive pain.


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