Pain Tolerance in Buprenorphine Maintenance Treatment

Buprenorphine maintenance treatment for opioid dependence may result in hyperalgesia and prevent morphine-associated antinociception.

Buprenorphine maintenance treatment for opioid dependence may result in hyperalgesia and prevent morphine-associated antinociception, according to preliminary findings published in Pain Medicine.

In this study, 12 patients maintained on stable doses of sublingual buprenorphine for 1.5 to 12 months and 10 healthy control patients were included. All study participants were pain free. Patients receiving buprenorphine maintenance treatment were categorized according to efficacious maintenance dose (2-8 mg; 9-15 mg; 16-22 mg; n=4 in each group).  

Two 1-hour-long intravenous morphine infusions (1 mg/mL) were administered to study participants to achieve 2 consecutive pseudo-steady-state plasma concentrations (80 ng/mL and 180 ng/mL for patients on buprenorphine; 11 ng/mL and 33 ng/mL for control subjects). Buprenorphine was administered to patients already on the drug 1 hour after the end of the second morphine infusion.

Nociception was assessed using the cold pressor test and electrical stimulation of the earlobe. In both tests, the time at which pain could no longer be tolerated was assessed (delay in removing one’s nondominant arm immersed in ice-cold water and request to cease electrical stimulation, respectively).

Pain tolerance assessed with the cold pressor test — but not with electrical stimulation — was lower in participants treated with buprenorphine compared with controls at baseline (17±2 seconds vs 34±6 seconds, respectively; P =.009). Morphine infusion increased pain tolerance in the cold pressor test in control patients (34±6 seconds to 52±11 seconds; P =.04), but not in patients on buprenorphine maintenance treatment.

In addition, patients on buprenorphine therapy vs controls had a reduced respiratory rate at baseline (14 breaths/min vs 17 breaths/min respectively; P =.03). This rate was further reduced in patients taking buprenorphine following morphine infusion (12 breaths/min; P <.01). In addition, at the end of morphine infusion, plasma morphine concentrations were higher in study participants on buprenorphine therapy vs controls (136±10 ng/mL vs 23±1 ng/mL, respectively).

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The investigators measured plasma buprenorphine concentrations only at the putative peak, potentially limiting the findings. Additionally, the small sample size of this study may prevent the ability to generalize the findings to the broader population receiving buprenorphine maintenance treatment.

“There is a need to explore alternative strategies for providing acute pain relief in buprenorphine (and methadone)-maintained patients,” concluded the study authors.

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Athanasos P, Ling W, Bochner F, White JM, Somogyi AA. Buprenorphine maintenance subjects are hyperalgesic and have no antinociceptive response to a very high morphine dose [published online March 5, 2018]. Pain Med. doi: 10.1093/pm/pny025