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The present study investigated pain trajectories of husbands and wives over their mid-later years, the grouping of these trajectories, and differences in baseline biopsychosocial profiles and health and well-being outcomes in later years across the pain trajectory groups.
Learn More >The current study used data from a clinical trial to identify variables that are associated with and/or mediate the beneficial effects of four psychological chronic pain treatments: one teaching patients self-hypnosis to reduce pain intensity (HYP), one teaching self-hypnosis to change thoughts about pain (hypnotic cognitive therapy, or HYP-CT), one teaching cognitive restructuring skills to change thoughts about pain (cognitive therapy, or CT), and one providing education about pain (ED; included as an active control condition). Of 17 possible mechanism variables examined, and with alpha not corrected for multiple comparisons, significant between-group differences were observed for three. Two of these (changes in beliefs about control over pain and number of days of skill practice) were supported as mediators of the beneficial effects of HYP, CT, or HYP-CT, relative to ED. Six mechanism variables evidenced significant pre- to post-treatment changes in the sample as a whole, without showing significant between-group differences. Pre- to post-treatment changes in all six were associated with improvements in pain interference, pain intensity, or both. In addition, participant ratings of therapeutic alliance at post-treatment were associated significantly with improvements in both pain intensity and pain interference in the sample as a whole. Thus, of the 17 possible mediators examined, there were relatively few that serve as mediators for the beneficial effects of specific treatments; a larger number of variables predicted treatment outcome overall. The extent to which these variables are treatment mediators (i.e., are responsible for, rather than merely associated with, treatment-related improvements) will require further research.
Learn More >Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect of cancer treatment, often associated with degeneration of sensory axons or their terminal regions. Presence of the slow Wallerian degeneration protein (WLD), or genetic deletion of sterile alpha and TIR motif containing protein 1 (SARM1), which strongly protect axons from degeneration after injury or axonal transport block, alleviate pain in several CIPN models. However, oxaliplatin can cause an acute pain response, suggesting a different mechanism of pain generation. Here, we tested whether the presence of WLD or absence of SARM1 protects against acute oxaliplatin-induced pain in mice after a single oxaliplatin injection. In BL/6 and Wld mice, oxaliplatin induced significant mechanical and cold hypersensitivities which were absent in Sarm1 mice. Despite the presence of hypersensitivity there was no significant loss of intraepidermal nerve fibers (IENFs) in the footpads of any mice after oxaliplatin treatment, suggesting that early stages of pain hypersensitivity could be independent of axon degeneration. To identify other changes that could underlie the pain response, RNA sequencing was carried out in DRGs from treated and control mice of each genotype. Sarm1 mice had fewer gene expression changes than either BL/6 or Wld mice. This is consistent with the pain measurements in demonstrating that Sarm1DRGs remain relatively unchanged after oxaliplatin treatment, unlike those in BL/6 and Wld mice. Changes in levels of four transcripts – Alas2, Hba-a1, Hba-a2, and Tfrc – correlated with oxaliplatin-induced pain, or absence thereof, across the three genotypes. Our findings suggest that targeting SARM1 could be a viable therapeutic approach to prevent oxaliplatin-induced acute neuropathic pain.
Learn More >Persistent post-mastectomy pain (PPMP) is a significant negative outcome occurring after breast surgery, and understanding which individual women are most at risk is essential to targeting of preventive efforts. The biopsychosocial model of pain suggests that factors from many domains may importantly modulate pain processing and predict the progression to pain persistence.
Learn More >The study evaluated if chronic musculoskeletal (MSK) pain predicts the severity of insomnia, and whether the effect is moderated by age, gender, and number of comorbid diseases in older people. An 18-month prospective study was performed within the framework of a community health program in Hong Kong. A total of 498 older people aged ≥ 60 with multimorbidity were recruited. The predictors included the presence of chronic MSK pain, pain measured by the Brief Pain Inventory (BPI), insomnia measured by baseline Insomnia Severity Index (ISI), and number of co-morbid diseases, age, and gender. The outcome was ISI repeated at 18 months. The moderators included age, gender, and number of comorbid diseases. Multivariate linear regression and moderation analysis were conducted. We found that the presence of chronic MSK pain (β = 1.725; 95% CI, 0.607-2.842; P < 0.01) predicted the severity of ISI, after controlling for age, gender, BMI, and the number of comorbid diseases. Participants with chronic MSK pain throughout the period had worse trend of improvement in ISI compared to those who were "pain-free" (β = 2.597; 95% CI, 1.311-3.882; P < 0.001). Age, gender, and number of comorbid diseases did not moderate the longitudinal relationship. We propose that pain management should prioritized in the prevention of insomnia.
Learn More >Cognitive-behavioral therapy (CBT) can reduce preoperative pain catastrophizing and may improve postsurgical pain outcomes. We hypothesized that CBT would reduce pain catastrophizing more than no-CBT controls and result in improved pain outcomes.
Learn More >Disrupted connectivity within visual, attentional and salience networks in the visual snow syndrome.
Here we investigate brain functional connectivity in patients with visual snow syndrome (VSS). Our main objective was to understand more about the underlying pathophysiology of this neurological syndrome. Twenty-four patients with VSS and an equal number of gender and age-matched healthy volunteers attended MRI sessions in which whole-brain maps of functional connectivity were acquired under two conditions: at rest while watching a blank screen and during a visual paradigm consisting of a visual-snow like stimulus. Eight unilateral seed regions were selected a priori based on previous observations and hypotheses; four seeds were placed in key anatomical areas of the visual pathways and the remaining were derived from a pre-existing functional analysis. The between-group analysis showed that patients with VSS had hyper and hypoconnectivity between key visual areas and the rest of the brain, both in the resting state and during a visual stimulation, compared with controls. We found altered connectivity internally within the visual network; between the thalamus/basal ganglia and the lingual gyrus; between the visual motion network and both the default mode and attentional networks. Further, patients with VSS presented decreased connectivity during external sensory input within the salience network, and between V5 and precuneus. Our results suggest that VSS is characterised by a widespread disturbance in the functional connectivity of several brain systems. This dysfunction involves the pre-cortical and cortical visual pathways, the visual motion network, the attentional networks and finally the salience network; further, it represents evidence of ongoing alterations both at rest and during visual stimulus processing.
Learn More >Prospective cohort study.
Learn More >Expectations contribute to cognitive pain modulation through opioidergically-mediated descending inhibition. Mindfulness meditation reduces pain independent of endogenous opioids, engaging unique corticothalamo-cortical mechanisms. However, it remains unknown whether expectations for pain-relief predict mindfulness-induced analgesia and if these expectations are modified by endogenous opioids.
Learn More >Transient Receptor Potential Melastatin 3 (TRPM3) is a heat-activated ion channel in primary sensory neurons of the dorsal root ganglia (DRG). Pharmacological and genetic studies implicated TRPM3 in various pain modalities, but TRPM3 inhibitors were not validated in TRPM3 mice. Here we tested two inhibitors of TRPM3 in male and female wild type and TRPM3 mice in nerve injury-induced neuropathic pain. We found that intraperitoneal injection of either isosakuranetin, or primidone reduced heat hypersensitivity induced by chronic constriction injury (CCI) of the sciatic nerve, in wild type, but not in TRPM3 mice. Primidone was also effective when injected locally in the hind paw, or intrathecally. Consistently, intrathecal injection of the TRPM3 agonist CIM0216 reduced paw withdrawal latency to radiant heat in wild type, but not in TRPM3 mice. Intraperitoneal injection of 2 mg/kg, but not 0.5 mg/kg isosakuranetin, inhibited cold and mechanical hypersensitivity in CCI, both in wild-type and TRPM3 mice, indicating a dose dependent off target effect. Primidone had no effect on cold sensitivity, and only a marginal effect on mechanical hypersensitivity. Genetic deletion or inhibitors of TRPM3 reduced the increase in the levels of the early genes cFos and pERK in the spinal cord and DRG in CCI mice, suggesting spontaneous activity of the channel. Intraperitoneal isosakuranetin also inhibited spontaneous pain related behavior in CCI in the conditioned place preference assay, and this effect was eliminated in TRPM3 mice. Overall our data indicate a role of TRPM3 in heat hypersensitivity and in spontaneous pain after nerve injury.Neuropathic pain is a major unsolved medical problem. The heat-activated TRPM3 ion channel is a potential target for novel pain medications, but it is not clear what pain modalities it plays roles in. Here we used a combination of genetic and pharmacological tools to assess the role of this channel in spontaneous pain, heat-, cold- and mechanical hypersensitivity in a nerve injury model of neuropathic pain in mice. Our findings indicate a role for TRPM3 in heat hyperalgesia, and spontaneous pain, but not in cold, and mechanical hypersensitivity. We also find that not only TRPM3 located in the peripheral nerve termini, but also TRPM3 in the spinal cord, or proximal segments of DRG neurons is important for heat hypersensitivity.
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