Pain
-
Randomized Controlled Trial
Hypnotic susceptibility modulates brain activity related to experimental placebo analgesia.
Identifying personality traits and neural signatures that predict placebo responsiveness is important, both on theoretical and practical grounds. In the present functional magnetic resonance imaging (fMRI) study, we performed multiple-regression interaction analysis to investigate whether hypnotic susceptibility (HS), a cognitive trait referring to the responsiveness to suggestions, explains interindividual differences in the neural mechanisms related to conditioned placebo analgesia in healthy volunteers. HS was not related to the overall strength of placebo analgesia. ⋯ During pain perception, activity in the regions reflecting attention/arousal (bilateral anterior thalamus/left caudate) and self-related processing (left precuneus and bilateral posterior temporal foci) was negatively related to the strength of the analgesic placebo response in subjects with higher HS, but not in subjects with lower HS. These findings highlight HS influences on brain circuits related to the placebo analgesic effects. More generally, they demonstrate that different neural mechanisms can be involved in placebo responsiveness, depending on individual cognitive traits.
-
Pain and sensitization are major issues in patients with osteoarthritis both before and after total knee arthroplasty (TKA) and revision TKA (re-TKA). The aim of this study was to assess sensitization in patients with and without chronic pain after re-TKAs. Twenty patients with chronic knee pain and 20 patients without pain after re-TKA participated. ⋯ Additionally, significant correlations between knee pain intensity and cuff PPTs, temporal summation, and CPM and between total duration of knee pain and temporal summation were found (P<.05). This study demonstrated widespread sensitization in patients with pain after re-TKA and highlighted the importance of ongoing nociceptive input for the chronification process. This has important implications for future revisions, and precautions should be taken if patients have widespread sensitization.
-
Randomized Controlled Trial
Specifying the nonspecific components of acupuncture analgesia.
It is well known that acupuncture has pain-relieving effects, but the contribution of specific and especially nonspecific factors to acupuncture analgesia is less clear. One hundred one patients who developed pain of ≥ 3 on a visual analog scale (VAS, 0 to 10) after third molar surgery were randomized to receive active acupuncture, placebo acupuncture, or no treatment for 30 min with acupuncture needles with potential for double-blinding. Patients' perception of the treatment (active or placebo) and expected pain levels (VAS) were assessed before and halfway through the treatment. ⋯ Expected pain levels accounted for significant and progressively larger amounts of the variance in pain ratings after both active and placebo acupuncture (up to 69.8%). This is the first study to show that under optimized blinding conditions, nonspecific factors such as patients' perception of and expectations toward treatment are central to the efficacy of acupuncture analgesia and that these factors may contribute to self-reinforcing effects in acupuncture treatment. To obtain an effect of acupuncture in clinical practice, it may therefore be important to incorporate and optimize these factors.
-
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by recurring abdominal pain associated with alterations in bowel habits. We hypothesized that patients with chronic visceral pain associated with IBS may have microstructural differences in the brain compared with healthy control subjects (HCs), indicative of long-term neural reorganization of chronic pain pathways and regions associated with sensory integration. In the current study we performed population-based voxel-wise diffusion tensor imaging (DTI) comparisons and probabilistic tractography in a large sample of phenotyped patients with IBS (n=33) and in HCs (n=93). ⋯ Sex differences in FA and MD were also observed in the patients but not in HCs. Probabilistic tractography in patients confirmed a higher degree of connectivity between the thalamus and prefrontal cortex, as well as between the medial dorsal thalamic nuclei and anterior cingulate cortex, and a lower degree of connectivity between the GP and thalamus. Together, these results support the hypothesis that patients with chronically recurring visceral pain from IBS have long-term microstructural changes within the brain, particularly in regions associated with integration of sensory information and corticothalamic modulation.
-
Randomized Controlled Trial Multicenter Study
A phase 2, double-blind, randomized, placebo-controlled, dose-escalation study to evaluate the efficacy, safety, and tolerability of naloxegol in patients with opioid-induced constipation.
Naloxegol (previously known as NKTR-118) is a peripherally acting μ-opioid receptor antagonist engineered using polymer conjugate technology in development as an oral, once-daily agent for the treatment of opioid-induced constipation (OIC). Eligible patients with OIC (n=207), defined as <3 spontaneous bowel movements (SBMs) per week with accompanying symptoms, on a stable opioid regimen of 30-1000 mg/day morphine equivalents for ≥ 2 weeks were randomized to receive 4 weeks of double-blind placebo or naloxegol (5, 25, or 50mg) once daily in sequential cohorts after a 1-week placebo run-in. The primary end point, median change from baseline in SBMs per week after week 1 of drug administration, was statistically significant for the 25- and 50-mg naloxegol cohorts vs placebo (2.9 vs 1.0 [P=0.0020] and 3.3 vs 0.5 [P=0.0001], respectively). ⋯ Similar AEs occurred with increased frequency and severity in the 50-mg cohort. There was no evidence of a statistically significant increase from baseline in pain, opioid use for the 25- and 50-mg cohorts, or centrally mediated opioid withdrawal signs and/or symptoms with naloxegol. These data demonstrate that once-daily oral naloxegol improves the frequency of SBMs compared with placebo and is generally well tolerated in this population of patients with OIC.