Buprenorphine maintenance subjects are hyperalgesic and have no antinociceptive response to a very high morphine dose

Objective. Acute pain management in opioiddependent persons is complicated because of tolerance and opioid-induced hyperalgesia. Very high doses of morphine are ineffective in overcoming opioid-induced hyperalgesia and providing antinociception to methadone-maintained patients in an experimental setting. Whether the same occurs in buprenorphine-maintained subjects is unknown. Design. Randomized double-blind placebo-controlled. Subjects were tested on two occasions, at least five days apart, once with intravenous morphine and once with intravenous saline. Subjects were tested at about the time of putative trough plasma buprenorphine concentrations. Setting. Ambulatory. Subjects. Twelve buprenorphine-maintained subjects: once daily sublingual dose (range 5 2–22 mg); no dose change for 1.5–12 months. Ten healthy controls. Methods. Intravenous morphine bolus and infusions administered over two hours to achieve two separate pseudo-steady-state plasma concentrations one hour apart. Pain tolerance was assessed by application of nociceptive stimuli (cold pressor [seconds] and electrical stimulation [volts]). Ten blood samples were collected for assay of plasma morphine, buprenorphine, and norbuprenorphine concentrations until three hours after the end of the last infusion; pain tolerance and respiration rate were measured to coincide with blood sampling times. Results. Cold pressor responses (seconds): baseline: control 34 6 6 vs buprenorphine 17 6 2 (P 5 0.009); morphine infusion-end: control 52 6 11(P 5 0.04), buprenorphine 17 6 2 (P> 0.5); electrical stimulation responses (volts): baseline: control 65 6 6 vs buprenorphine 53 6 5 (P 5 0.13); infusion-end: control 74 6 5 (P 5 0.007), buprenorphine 53 6 5 (P> 0.98). Respiratory rate (breaths per minute): baseline: control 17 vs buprenorphine 14 (P 5 0.03); infusion-end: control 15 (P 5 0.09), buprenorphine 12 (P< 0.01). Infusion-end plasma morphine concentrations (ng/mL): control 23 6 1, buprenorphine 136 6 10. Conclusions. Buprenorphine subjects, compared with controls, were hyperalgesic (cold pressor test), did not experience antinociception, despite high plasma morphine concentrations, and experienced respiratory depression. Clinical implications are discussed.Peter Athanasos, Walter Ling, Felix Bochner, Jason M. White, and Andrew A. Somogy

Pain: the new co-morbidity

http://www.ncbi.nlm.nih.gov/pubmed/1804424

Withdrawal hyperalgesia after acute opioid physical dependence in nonaddicted humans: A preliminary study

Copyright © 2003 American Pain Society. Published by Elsevier Science (USA).Hyperalgesia has been demonstrated to be a cardinal sign of physical withdrawal from opioids in preclinical models for more than 30 years, although few empirical data exist to support its occurrence in humans. In this preliminary study we used the acute opioid physical dependence (APD) model to test for the presence of hyperalgesia to experimental cold-pressor pain in 4 healthy non–opioid-dependent men via 3 different pretreatment opioid administration protocols previously demonstrated to induce APD (morphine 18 mg/70 kg intramuscular, morphine 10 mg/70 kg intravenous, hydromorphone 2 mg/70 kg intravenous), repeated on 2 separate occasions, and placebo. Cold-pressor pain threshold and tolerance were examined before opioid administration and 5 and 15 minutes after precipitated withdrawal with naloxone 10 mg/70 kg intravenous. Paired t tests comparing change scores between the opioid pretreatments and placebo showed that pain threshold and tolerance to the cold-pressor uniformly decreased across all APD induction methods, and the effect size was large (~70% of baseline) and reproducible. These findings provide initial support for the existence of opioid-induced hyperalgesia, which has been conceptualized as a coexisting opponent process to opioid-induced analgesia and proposed to be an alternative explanation for the development of analgesic tolerance to opioids.http://www.sciencedirect.com/science/journal/1526590

The impact of childhood trauma: preliminary findings

The article focuses on research documenting the importance of child development and childhood trauma in the occurrence of mental health, drug and alcohol issues in adulthood.Peter Athanasos, Rose Neild and Charlotte De Crespign

Heatwave, mental health-substance use

Series: Mental health-substance use, Book

Substance use and dependency

3rd Editio