Predicting the analgesic effect to oxycodone by ‘static’ and ‘dynamic’ quantitative sensory testing in healthy subjects

Abstract

The large inter-individual variability in the magnitude of analgesia in response to opioids and the high prevalence of adverse events associated with their use underline the clinical importance of being able to predict who will or will not respond to opioid treatment. The present study used both static and dynamic quantitative sensory testing (QST) on 40 healthy volunteers in order to test whether this methodology can predict the analgesic effects of oral oxycodone, as compared to a placebo, on latency to onset, pain intensity, and tolerance to the cold pressor test (CPT). Static QST consisted of measuring heat and cold pain thresholds. Dynamic QST included measurements of the magnitude of the diffuse noxious inhibitory control (DNIC)-like effect and of temporal summation (TS). Results showed that oxycodone, but not the placebo, significantly elevated the latency and tolerance to cold pain and significantly reduced pain intensity. The static QST results showed that heat pain thresholds predicted the magnitude of reduction in pain intensity in response to oxycodone treatment (F((1,22))=5.63, p=0.027, R(2)=0.17). The dynamic QST results showed that TS predicted the effect of oxycodone on the tolerance to CPT (F((1,38))=9.11, p=0.005, R(2)=0.17). These results suggest that both static and dynamic QST have the potential to be useful in the prediction of the response to opioid treatment.

Inhibition of TRPM8 Channels Reduces Pain in the Cold Pressor Test in Humans

“…Thus, the third cohort was dosed to study the effect of PF-05105679 on the cold pressor test at 600 and 900 mg. From the pharmacokinetic analysis of the 300 mg, this maximum plasma concentration for this dose would be observed at the second cold pressor test evaluation with the 900-mg dose, and thus, was not tested in the efficacy arm of the study. PF-05105679 provided similar efficacy to the active comparator oxycodone (20 mg), the effects of which were consistent with previous studies with this opioid (Zwisler et al, 2009;Eisenberg et al, 2010). The differing time course of analgesia for both drugs is consistent with their pharmacokinetic profile.…”

Endogenous opioid function mediates the association between laboratory-evoked pain sensitivity and morphine analgesic responses

“…In a clinical trial examining the effects of daily morphine administration in postherpetic neuralgia patients over a 6 week period, greater morphine-related reductions in clinical pain over the trial were observed in patients showing lower baseline (pre-drug) sensitivity to acute heat pain 18 . The only prior controlled laboratory study examining the influence of pre-drug acute pain sensitivity on responses to a single opioid analgesic dose (in healthy individuals) found similar results, reporting that lower pre-drug laboratory heat pain sensitivity predicted greater reductions in cold pressor pain responses following oxycodone administration 21 . While intriguing, neither of the existing studies of this issue directly controlled for placebo effects in predictive analyses.…”

“…One individual difference factor previously reported to predict opioid analgesic responses in humans is sensitivity to laboratory evoked pain stimuli 18,21 . In a clinical trial examining the effects of daily morphine administration in postherpetic neuralgia patients over a 6 week period, greater morphine-related reductions in clinical pain over the trial were observed in patients showing lower baseline (pre-drug) sensitivity to acute heat pain 18 .…”

Role of endogenous pain modulation in chronic pain mechanisms and treatment

“…Alpha2 agonists inhibit CPM, in a dose-dependent manner. 4 The ability of CPM to predict analgesic effect was examined in healthy controls by Eisenberg et al, 22 finding that CPM did not predict efficacy of oxycodone, whereas heat pain thresholds (HPT) and TS did. Use of CPM in prediction of analgesic effect was reported by these authors, as described above.…”