Human Studies

To investigate the effectiveness of sufentanil patient-controlled intravenous analgesia pump (PCIA) and background infusion in patients of post-cesarean analgesia.

Discrimination of cues predicting non-nociceptive/nociceptive stimuli is essential for predicting whether a non-painful or painful stimulus will be administered and for eliciting placebo/nocebo (pain reduction/pain enhancement) effects. Dysfunction of the neural system involved in placebo effects has been implicated in the pathology of chronic pain, while female sex is one of the important risk factors for development of chronic pain in young adults. The dorsolateral prefrontal cortex (dl-PFC) is suggested to be involved in placebo effects and is sensitive to sex and age. In this study, to examine the neural mechanisms by which sex and age alter placebo and nocebo effects, we analyzed cerebral hemodynamic activities in the dl-PFC in different sex and age groups during a differential conditioning task. During the training session, two different sounds were followed by low- and high-intensity electrical shocks. In the following recording session, electrical shocks, the intensity of which was mismatched to the sounds, were occasionally administered to elicit placebo and nocebo effects. In young female participants, both placebo effects and hemodynamic responses to the conditioned sounds in the right dl-PFC were significantly lower than those in elderly female participants, while there were no age differences in male participants. The hemodynamic responses to the sound paired with the safe stimulus in the right dl-PFC were significantly correlated with placebo effects, except in the young female group. These results suggest that blunted placebo effects in the young female participants are ascribed to blunted responses to the sound associated with the safe stimulus in the right dl-PFC, and that sex- and age-related factors may alter the responsiveness of the right dl-PFC to associative cues predicting a safe stimulus.

The aim of the study is to explore the relationship between the extrusion of the meniscus bearing and postoperative persistent pain of Oxford unicompartmental knee arthroplasty. Patients undertaking Oxford UKA from January 2019 to June 2020 were retrospectively analyzed. Intraoperatively, the displacement and movement trajectory of the meniscus bearing was recorded by the specially designed gridding mold of the tibial component. The k-means clustering analysis was applied based on the incidence of postoperative persistent knee pain and the bearing extrusion distance. The intraoperative meniscus bearing movement trajectories were analyzed between the two groups and the patients' clinical outcomes and radiographic assessments. The k-means clustering analysis indicated that the extrusion of the bearing of 5 mm was the grouping standard. There were 27 patients with 30 knees in the extrusion group and 58 patients with 68 knees in the non-extrusion group. The proportion of optimal bearing movement trajectories in the extrusion group was significantly lower than that in the non-extrusion group ( < 0.05). Postoperative persistent knee pain occurred in six cases (6.1%), with four and two cases in the extrusion and non-extrusion groups, respectively. The incidence of postoperative persistent knee pain in the extrusion group was higher than that of the non-extrusion group ( < 0.05). Radiographic assessment showed that the continuity of the femoral and tibial components in the extrusion group was greater than that in the non-extrusion group ( < 0.05). However, there were no differences in pre- and postoperative HKAA, the varus/valgus degree of both femoral and tibial components, and the flexion/extension angles of the femoral component, and the tibial slope also showed no statistical difference ( > 0.05). For Oxford mobile-bearing UKA, the extrusion of meniscus bearing over 5 mm may increase the incidence of postoperative persistent knee pain, while the improvement of the bearing movement trajectory can effectively reduce this complication.

We assessed the potential of using EEG to detect cold thermal pain in adolescents with and without chronic musculoskeletal pain.

Although chronic pain (CP) is common, little is known about its economic burden in Alberta, Canada.

Pain is thought to be influenced by the threat value of the particular context in which it occurs. However, the mechanisms by which a threat achieves this influence on pain are unclear. Here, we explore how threat influences experimentally-induced secondary hyperalgesia, which is thought to be a manifestation of central sensitization. We developed an experimental study to investigate the effect of a manipulation of threat on experimentally-induced secondary hyperalgesia in 26 healthy human adults (16 identifying as female; 10 as male). We induced secondary hyperalgesia at both forearms using high-frequency electrical stimulation. Prior to the induction, we used a previously successful method to manipulate threat of tissue damage at one forearm (threat site). The effect of the threat manipulation was determined by comparing participant-rated anxiety, perceived threat, and pain during the experimental induction of secondary hyperalgesia, between the threat and control sites. We hypothesized that the threat site would show greater secondary hyperalgesia (primary outcome) and greater surface area (secondary outcome) of induced secondary hyperalgesia than the control site. Despite a thorough piloting procedure to test the threat manipulation, our data showed no main effect of site on pain, anxiety, or threat ratings during high-frequency electrical stimulation. In the light of no difference in threat between sites, the primary and secondary hypotheses cannot be tested. We discuss reasons why we were unable to replicate the efficacy of this established threat manipulation in our sample, including: (1) competition between threats, (2) generalization of learned threat value, (3) safety cues, (4) trust, and requirements for participant safety, (5) sampling bias, (6) sample-specific habituation to threat, and (7) implausibility of (sham) skin examination and report. Better strategies to manipulate threat are required for further research on the mechanisms by which threat influences pain.

Chronic pain in multiple sclerosis is common and difficult to treat. Its mechanisms remain incompletely understood. Dysfunction of the descending pain modulatory system is known to contribute to human chronic pain conditions. However, it is not clear how alterations in executive function influence this network, despite healthy volunteer studies linking function of the descending pain modulatory system, to cognition. In adults with multiple sclerosis-associated chronic neuropathic limb pain, compared to those without pain, we hypothesized altered functional connectivity of the descending pain modulatory system, coupled to executive dysfunction. Specifically we hypothesized reduced mental flexibility, because of potential importance in stimulus reappraisal. To investigate these hypotheses, we conducted a case-control cross-sectional study of 47 adults with relapsing remitting multiple sclerosis (31 with chronic neuropathic limb pain, 16 without pain), employing clinical, neuropsychological, structural, and functional MRI measures. We measured brain lesions and atrophy affecting descending pain modulatory system structures. Both cognitive and affective dysfunctions were confirmed in the chronic neuropathic limb pain group, including reduced mental flexibility (Delis Kaplan Executive Function System card sorting tests  < 0.001). Functional connectivity of rostral anterior cingulate and ventrolateral periaqueductal gray, key structures of the descending pain modulatory system, was significantly lower in the group experiencing chronic neuropathic pain. There was no significant between-group difference in whole-brain grey matter or lesion volumes, nor lesion volume affecting white matter tracts between rostral anterior cingulate and periaqueductal gray. Brainstem-specific lesion volume was higher in the chronic neuropathic limb pain group ( = 0.0017). Differential functional connectivity remained after correction for brainstem-specific lesion volume. Gabapentinoid medications were more frequently used in the chronic pain group. We describe executive dysfunction in people with multiple sclerosis affected by chronic neuropathic pain, along with functional and structural MRI evidence compatible with dysfunction of the descending pain modulatory system. These findings extend understanding of close inter-relationships between cognition, function of the descending pain modulatory system, and chronic pain, both in multiple sclerosis and more generally in human chronic pain conditions. These findings could support application of pharmacological and cognitive interventions in chronic neuropathic pain associated with multiple sclerosis.

Spinal fusion surgery is a common and painful musculoskeletal surgery performed in the adolescent population. Despite the known risk for developing chronic postsurgical pain, few perioperative psychosocial interventions have been evaluated in this population, and none have been delivered remotely (via the Internet) to improve accessibility.