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Objective: Use of opioids for pain management has increased over the past decade; however, inadequate analgesic response is common. Genetic variability may be related to opioid efficacy, but due to the many possible combinations and variables, statistical computations may be difficult. This study investigated whether data processing with support vector machine learning could predict required opioid dose in cancer pain patients, using genetic profiling. Eighteen single nucleotide polymorphisms (SNPs) within the μ and δ opioid receptor genes and the catechol-O-methyltransferase gene were selected for analysis. Results: Data from 1237 cancer pain patients were included in the analysis. Support vector machine learning did not find any associations between the assessed SNPs and opioid dose in cancer pain patients, and hence, did not provide additional information regarding prediction of required opioid dose using genetic profiling.

Opioids are increasingly used for treatment of chronic pain. However, they are only effective in a subset of patients and have multiple side effects. Thus, studies using biomarkers for response are highly warranted. The current study prospectively examined 63 opioid-naïve patients initiating opioid use for diverse types of chronic pain at five European centers. Quantitative sensory testing, electroencephalography (EEG) recordings, and assessment of pain catastrophizing were performed prior to treatment. The co-primary outcomes were change from baseline in ratings of chronic pain and quality of life after 14 days of opioid treatment. Secondary outcomes included patient's global impression of clinical change and side effects. Logistic regression models adjusted for age and sex were used to identify biomarkers predictive for successful treatment, defined as at least a 30% reduction in average pain intensity or an improvement in quality of life of at least 10 scale points. Fifty-nine patients (94%) completed the study. The mean age was 55 ± 16 years and 69% were females. Pain reduction was predicted by cold pain intensity (OR: 0.69; P = 0.01), pain catastrophizing (OR: 0.82; P = 0.03), relative delta (OR: 0.76; P = 0.03) and beta EEG activity (OR: 1.18; P = 0.04) induced by experimental cold pain. None of the study variables were related to improvement in quality of life. For the first time, individual pain processing characteristics have been linked to opioid response in a mixed chronic pain population. This has the potential to personalize treatment of chronic pain and restrict opioid use to patients with high likelihood for response.

Tine Maria Hansen,1,2 Esben Bolvig Mark,1,3 Søren Schou Olesen,2,3 Mikkel Gram,3 Jens Brøndum Frøkjær,1,2 Asbjørn Mohr Drewes2,3 1Mech-Sense, Department of Radiology, Aalborg University Hospital, 2Department of Clinical Medicine, Aalborg University, 3Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark Objective: The aim of the present study was to characterize the cortical source generators evoked by experimental tonic pain. Methods: Electroencephalography (EEG) was recorded on two separate days during rest and with immersion of the hand in ice water for 2 minutes (cold pressor test). Exact low-resolution brain electromagnetic tomography source localization was performed in 31 healthy volunteers to characterize the cortical source generators. Results: Reliability was high in all eight frequency bands during rest and cold pressor conditions (intraclass coefficients =0.47–0.83 in the cingulate and insula). Tonic pain increased cortical activities in the delta (1–4 Hz), theta (4–8 Hz), beta1 (12–18 Hz), beta2 (18–24 Hz), beta3 (24–32 Hz), and gamma (32–60 Hz) bands (all P<0.011) in widespread areas mainly in the limbic system, whereas decreased cortical activities were found in cingulate and pre- and postcentral gyri in the alpha2 (10–12 Hz) band (P=0.007). The pain intensity was correlated with cingulate activity in the beta2, beta3, and gamma bands (all P<0.04). Conclusion: Source localization of EEG is a reliable method to estimate cortical source generators. Activities in different brain regions, mainly in the limbic system, showed fluctuations in various frequency bands. Cingulate changes were correlated with pain intensity.Significance: This method might add information to the objective assessment of the cortical pain response in future experimental pain studies. Ke

Objective Opioid treatment is associated with numerous gastrointestinal adverse effects collectively known as opioid-induced bowel dysfunction (OIBD). Most current knowledge of the pathophysiology derives from animal studies limited by species differences and clinical studies, which have substantial confounders that make evaluation difficult. An experimental model of OIBD in healthy volunteers in a controlled setting is therefore highly warranted. The aim of this study was to assess bowel function in healthy volunteers during opioid treatment using subjective and objective methods. Methods Twenty-five healthy men were assigned randomly to oxycodone or placebo for 5 days in a cross-over design. The analgesic effect was assessed with muscle pressure algometry and adverse effects were measured using questionnaires including the bowel function index, gastrointestinal symptom rating scale, patient assessment of constipation symptoms and the Bristol stool form scale. Colorectal volumes were determined using a newly developed MRI method. Results Compared with baseline, oxycodone increased pain detection thresholds by 8% (P= 0.02). Subjective OIBD was observed as increased bowel function index (464% increase; P< 0.001), gastrointestinal symptom rating scale (37% increase; P< 0.001) and patient assessment of constipation symptoms (198% increase; P< 0.001). Objectively, stools were harder and drier during oxycodone treatment (P< 0.001) and segmental colorectal volumes increased in the caecum/ascending colon by 41% (P =0.005) and in the transverse colon by 20% (P= 0.005). No associations were detected between questionnaire scores and colorectal volumes. Conclusion Experimental OIBD in healthy volunteers was induced during oxycodone treatment. This model has potential for future interventional studies to discriminate the efficacies of different laxatives, peripheral morphine antagonists and opioid treatments.