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Background: Measures of physical activity and pain-related patient-reported outcomes are important components of patient recovery after surgery. However, little is known about their association in the early post-operative period. This study aims to increase this knowledge. Our primary objective was to determine the association between average pain intensity and activity (in steps) 1 week after surgery. Secondary objectives were the association of activity with other patient-reported outcomes, age, sex, comorbidities and body mass index., Methods: Data were obtained from the PROMPT sub-project of IMI-PainCare. Patients after breast and endometriosis-related surgery, sternotomy and total knee arthroplasty completed pain-related outcomes questionnaires and wore an ActiGraph activity-tracking device. We correlated steps with average pain intensity on post-operative days 6 and 7. Secondary analyses were done using correlations and t-tests., Results: In 284 cases, there was no statistically significant correlation between steps and average pain intensity. In addition, none of the 28 secondary analyses showed a statistically significant result., Conclusions: Pain-related patient-reported outcome measures and physical activity are separate entities. Both should be measured after surgery to assess patient recovery and to identify treatment deficiencies., Significance Statement: Measuring recovery is a multi-dimensional challenge. After surgery, clinicians need to be aware that neither pain intensity nor activity levels tell the whole story. Each can hint to problems and treatment requirements., (© 2024 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation ‐ EFIC ®.)

Background: There is increasing evidence for oxytocin as a neurotransmitter in spinal nociceptive processes. Hypothalamic oxytocinergic neurons project to the spinal dorsal horn, where they activate GABA-ergic inhibitory interneurons. The present study tested whether the long-acting oxytocin-analogue carbetocin has anti-nociceptive effects in multi-modal experimental pain in humans., Methods: Twenty-five male volunteers received carbetocin 100 mcg and placebo (0.9% NaCl) on two different sessions in a randomized, double-blinded, cross-over design. Multi-modal quantitative sensory testing (QST) including a model of capsaicin-induced hyperalgesia and allodynia were performed at baseline and at 10, 60 and 120 min after drug administration. QST data were analysed using mixed linear and logistic regression models. Carbetocin plasma concentrations and oxytocin receptor genotypes were quantified and assessed in an exploratory fashion., Results: An anti-nociceptive effect of carbetocin was observed on intramuscular electrical temporal summation (estimated difference: 1.26 mA, 95% CI 1.01 to 1.56 mA, p = .04) and single-stimulus electrical pain thresholds (estimated difference: 1.21 mA, 95% CI 1.0 to 1.47 mA, p = .05). Furthermore, the area of capsaicin-induced allodynia was reduced after carbetocin compared to placebo (estimated difference: -6.5 cm 2 , 95% CI -9.8 to -3.2 cm 2 , p < .001)., Conclusions: This study provides evidence of an anti-nociceptive effect of carbetocin on experimental pain in humans., Significance: This study provides evidence of the anti-nociceptive effect of intravenous administration of the oxytocin agonist carbetocin in healthy male volunteers., (© 2021 European Pain Federation - EFIC®.)

Background: Drugs are prescribed for chronic low back pain without knowing in advance whether a patient will respond to them or not. Quantitative sensory tests (QST) can discriminate patients according to sensory phenotype, possibly reflecting underlying mechanisms of pain processing. QST may therefore be a screening tool to identify potential responders to a certain drug. The aim of this study was to investigate whether QST can predict analgesic effects of oxycodone, imipramine and clobazam in chronic low back pain., Methods: Oxycodone 15 mg (n = 50), imipramine 75 mg (n = 50) and clobazam 20 mg (n = 49) were compared to active placebo tolterodine 1 mg in a randomized, double-blinded, crossover fashion. Electrical, pressure and thermal QST were performed at baseline and after 1 and 2 h. Pain intensity was assessed on a 0-10 numeric rating scale every 30 min for up to 2 h. The ability of baseline QST to predict pain reduction after 2 h was analysed using linear mixed models. Genetic variants of drug-metabolizing enzymes and genes affecting pain sensitivity were examined as covariables., Results: No predictor of analgesic effect was found for oxycodone and clobazam. Thermal QST was associated with analgesic effect of imipramine: patients more sensitive to heat or cold were more likely to experience an effect of imipramine. Pharmacogenetic variants and pain-related candidate genes were not associated with drug efficacy., Conclusions: Thermal QST have the potential to predict imipramine effect in chronic low back pain. Oxycodone and clobazam effects could not be predicted by any of the selected QST or genetic variants., Significance: Predicting drug efficacy in chronic low back pain remains difficult. There is some evidence that patients more sensitive to heat and cold pain respond better to imipramine., (© 2018 European Pain Federation - EFIC®.)

The mu-opioid receptor (MOR1) is a target of endogenous and exogenous opioids and plays a pivotal role for anesthesia and analgesia. Variations in the 5' flanking sequence of the mu-opioid receptor gene may influence transcriptional regulation and ultimately alter protein expression of MOR1. In the present study we investigated the influence of eight single nucleotide polymorphisms (SNP) within the mu-opioid receptor promoter on promoter activity and evaluated the frequencies of the relevant SNPs in 700 patients under opioid medication. Reporter-gene-constructs were created by means of PCR and site directed mutagenesis, testing eight SNPs previously described. The neuroblastoma cell line SHSY5Y was used for transfection and promoter activity was estimated by luciferase activity. Of the eight reporter gene constructs employed to test genomic variations, two produced a significant change in luciferase activity when compared to wild-type constructs. The G-554A variation located within a known NFkB binding element resulted in a decreased activity whereas the A/G base exchange at position -1320 showed an increased luciferase activity. This particular variant generated a myeloid zinc finger (MZF1) cis-acting element known to impact transcription. The allele frequency of the -1320G variant was 0.21% in 700 Caucasian patients under opioid medication in contrast to 9.1% reported previously in drug addicted African Americans. Because of this unexpected low frequency an association analysis to opioid requirements and effects of mu-opioid receptor agonists was not feasible. In conclusion, transcriptional regulation of MOR1 is modified by two genetic variations at positions -554 and -1320 of the mu-opioid receptor promoter. Individuals presenting these variations may have an altered level of MOR expression. A possible association of these genomic variants on efficacy and side effects of opioid treatment in different ethnic groups has to be elucidated.