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Background: Tapentadol is a combined opioid agonist and norepinephrine reuptake inhibitor with fewer gastrointestinal side effects at equianalgesic doses compared with classical strong opioids. Previous studies on tapentadol have included multi‐morbid patients in whom confounders exclude detailed assessment of the mechanistic effects and strict comparison with other opioids or placebo. This study aimed at investigating the effects of tapentadol and oxycodone on gastrointestinal motility and gastrointestinal side effects. Methods: 21 healthy males participated in a randomized, double‐blind, placebo‐controlled, crossover study. Tapentadol (50 mg twice daily), oxycodone (10 mg twice daily), or placebo tablets were administered for 14 days. Segmental gastrointestinal transit times and colonic motility parameters were measured with electromagnetic capsules. Gastrointestinal side effects were assessed using questionnaires. Key Results: During dosing with tapentadol, gastrointestinal side effects and motility parameters were on placebo level. Compared with tapentadol, oxycodone increased whole gut transit time by 17.9 hours (p =.015) and rectosigmoid transit time by 6.5 hours (p =.005). Compared with tapentadol, oxycodone also reduced long, fast antegrade colonic movements (p =.001). In comparison with placebo, oxycodone prolonged whole gut transit time by 31.6 hours, (p <.001). Moreover, less long, fast antegrade colonic movements (p =.002) were observed during oxycodone. For oxycodone only, slow colonic movements were associated with gastrointestinal side effects. Conclusions & Inferences: In this mechanistic study, tapentadol caused significantly less colonic dysmotility and gastrointestinal side effects as compared with oxycodone in equianalgesic doses. [ABSTRACT FROM AUTHOR]

Background and aims: Offset analgesia (OA) is a pain modulating mechanism described as a disproportionately large decrease in pain intensity evoked by a minor decrease in stimulus intensity. Precise mechanisms of OA are still not elucidated and studies are needed to evaluate factors modulating OA. The aim of this study was to investigate OA before and during tonic cold pain (thought to induce descending inhibition), in a group of healthy volunteers. Methods: A randomized, crossover study was performed in 17 healthy participants (8 males and 9 females). The OA paradigm lasted 35 s and was induced by the traditional method using thermal stimulation applied to the forearm. A constant control heat stimulus (CTL) paradigm was used as control to assess adaptation. Pain intensity was assessed continuously. For induction of tonic cold pain, the participants immersed their hand into 2°C water for 2 min. After 1 min and 25 s, the heat stimulation (OA or CTL paradigm) was repeated to assess the modulatory effect of the cold pressor test. Results: It was possible to induce OA both before and during the cold pressor test. Tonic cold pain modulated the peak pain reported during both the OA (p=0.015) and CTL paradigms (p=0.001) reflecting endogenous pain modulation. However, the magnitude of OA was not modulated by tonic cold pain (p>0.05). Conclusions: The offset analgesia magnitude was not modulated by simultaneously tonic cold pain, thought to reflect another endogenous pain modulation mechanism. Implications: Neither offset analgesia magnitude nor adaptation were modulated by cold pressor induced endogenous analgesia. This could be explained by the fact, that offset analgesia was already at maximum in healthy participants. Hence, offset analgesia may not be a suitable assessment tool to investigate modulation induced by experimental methods or pharmacology in healthy participants. [ABSTRACT FROM AUTHOR]

Inconsistencies between species has stunted the progress of developing new analgesics. To increase the success of translating results between species, improved comparable models are required. Twelve rats received rectal balloon distensions on 2 different days separated by 24.3 (SD 24.6) days. Rectal balloon distensions were also performed in 18 humans (mean age: 34 yr; range: 21–56 yr; 12 men) on two separate occasions, separated by 9.3 (SD 5.5) days. In rats, cerebral evoked potentials (CEPs) were recorded by use of implanted skull-electrodes to distension pressure of 80 mmHg. In humans surface electrodes and individualized pressure, corresponding to pain detection threshold, were used. Comparison of morphology was assessed by wavelet analysis. Within- and between-day reproducibility was assessed in terms of latencies, amplitudes, and frequency content. In rats CEPs showed triphasic morphology. No differences in latencies, amplitudes, and power distribution were seen within or between days (all P ≥ 0.5). Peak-to-peak amplitude between the first positive and negative potential were the most reproducible characteristic within and between days (evaluated by intraclass correlation coefficients, ICC) (ICC = 0.99 and ICC = 9.98, respectively). In humans CEPs showed a triphasic morphology. No differences in latencies, amplitudes, or power distribution were seen within or between days (all P ≥ 0.2). Latency to the second negative potential (ICC = 0.98) and the second positive potential (ICC = 0.95) was the most reproducible characteristic within and between days. A unique and reliable translational platform was established assessing visceral sensitivity in rats and humans, which may improve the translational process of developing new drugs targeting visceral pain. [ABSTRACT FROM AUTHOR]

Chronic pancreatitis affects many individuals around the world, and the study of the underlying mechanisms leading to better treatment possibilities are important tasks. Therefore, animal models are needed to illustrate the basic study of pancreatitis. Recently, animal models of acute and chronic pancreatitis have been thoroughly reviewed, but few reviews address the important aspect on the translation of animal studies to human studies. It is well known that pancreatitis is associated with epigastric pain, but the understanding regarding to mechanisms and appropriate treatment of this pain is still unclear. Using animal models to study pancreatitis associated visceral pain is difficult, however, these types of models are a unique way to reveal the mechanisms behind pancreatitis associated visceral pain. In this review, the animal models of acute, chronic and un-common pancreatitis are briefly outlined and animal models related to pancreatitis associated visceral pain are also addressed.