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Optimizing long-term outcomes of exposure for chronic primary pain from the lens of learning theory.
Exposure in vivo is a theory-driven and widely used treatment to tackle functional disability in people with chronic primary pain. Exposure is quite effective; yet, in line with exposure outcomes for anxiety disorders, a number of patients may not profit from it, or relapse. In this focus article, we critically reflect on the current exposure protocols in chronic primary pain, and provide recommendations on how to optimize them. We propose several adaptations that are expected to strengthen inhibitory learning and/or retrieval of the extinction memory, thus likely decreasing relapse. We summarise the limited, but emerging experimental data in the pain domain, and draw parallels with experimental evidence in the anxiety literature. Our reflections and suggestions pertain to the use of the fear hierarchy, reassurance, positive psychology interventions, exposure with a range of stimuli and within different contexts, and the use of safety behaviours during treatment, as well as associating the fear-inducing stimuli with novel outcomes. In addition, we reflect on the importance of specifically tackling (the return of) pain-related avoidance behaviour with techniques such as disentangling fear from avoidance and reinforcing approach behaviours. Finally, we discuss challenges in the clinical application of exposure to improve functioning in chronic primary pain and possible avenues for future research. Perspectives: Inspired by recent advances in learning theory and its applications on the treatment of anxiety disorders, we reflect on the delivery of exposure treatment for chronic primary pain and propose strategies to improve its long-term outcomes.
Learn More >Evaluate the Impact Stratification Score (ISS) measure of low back pain impact that assesses physical function, pain interference, and pain intensity.
Learn More >We sought to investigate the patient experience of telemedicine for headache care during the coronavirus disease 2019 (COVID-19) pandemic.
Learn More >The current study introduces a new paradigm for exploring cognitive factors in pain. Interacting with virtual objects via embodied avatar hands increased the illusion of "being there" in the virtual world, increased VR analgesia for acute pain, and reduced accuracy on an attention demanding task. Twenty-four healthy volunteer college students participated in this within-subject randomized crossover design study. During Phase 1, each participant received brief thermal pain stimuli during interactive embodied avatar VR vs. passive VR (no avatar and no interactivity), VR treatment order randomized. After each pain stimulus, participants provided subjective 0-10 ratings of pain. Compared to the passive VR condition, during the interactive avatar VR, participants reported significant reductions in (1) worst pain, (2) pain unpleasantness, (3) time thinking about pain and (4). they had significantly more fun during the pain stimulus (p = .000 for each). During Phase 2, participants performed a divided attention task in each of the two VR conditions. Participants made significantly more errors on the divided attention task during the interactive avatar VR condition, compared to passive VR, implicating an attention mechanism for how virtual reality reduces pain and helping understand how VR influences pain perception.Trial registration: NCT04245475. Date of registration: 29/01/2020.
Learn More >Migraine is a common neurological disease that is often accompanied by psychiatric comorbidities. However, the relationship between abnormal brain function and psychiatric comorbidities in migraine patients remains largely unclear. Therefore, the present study sought to explore the correlations between the resting-state functional deficits and psychiatric comorbidities in migraine without aura (MwoA) patients.
Learn More >It has been hypothesised that attentional bias to environmental threats can contribute to persistent pain. It is unclear whether people with acute low back pain (LBP) have an attentional bias to environmental threats. We investigated if attentional bias of threat related words is different in people with acute LBP and pain-free controls.
Learn More >Application of spatially interlaced innocuous warm and cool stimuli to the skin elicits illusory pain, known as the thermal grill illusion (TGI). This study aimed to discriminate the underlying mechanisms of central and peripheral neuropathic pain focusing on pain quality, which is considered to indicate the underlying mechanism(s) of pain. We compared pain qualities in central and peripheral neuropathic pain with reference to pain qualities of TGI-induced pain.
Learn More >The anesthetic ketamine after intravenous dosing is nearly completely metabolized to R- and S-stereoisomers of the active norketamine (analgesic, psychoactive) and 2,6-hydroxynorketamine (potential analgesic, antidepressant) as well as the inactive dehydronorketamine. Oral administration favors the formation of 2,6-hydroxynorketamines via extensive presystemic metabolism. The authors hypothesized that plasma exposure to 2,6-hydroxynorketamines relative to the psychoactive ketamine is greater after prolonged-release ketamine tablets than it is after intravenous ketamine.
Learn More >σ-1 receptors (σR) modulate nociceptive signaling, driving the search for selective antagonists to take advantage of this promising target to treat pain. In this study, a new series of benzylpiperazinyl derivatives has been designed, synthesized, and characterized for their affinities toward σR and selectivity over the σ-2 receptor (σR). Notably, 3-cyclohexyl-1-{4-[(4-methoxyphenyl)methyl]piperazin-1-yl}propan-1-one () showed the highest σR receptor affinity ( σ = 1.6 nM) among the series with a significant improvement of the σR selectivity ( σ/ σ 886) compared to the lead compound ( σ/ σ 432). Compound was further tested in a mouse formalin assay of inflammatory pain and chronic nerve constriction injury (CCI) of neuropathic pain, where it produced dose-dependent (3-60 mg/kg, i.p.) antinociception and anti-allodynic effects. Moreover, compound demonstrated no significant effects in a rotarod assay, suggesting that this σR antagonist did not produce sedation or impair locomotor responses. Overall, these results encourage the further development of our benzylpiperazine-based σR antagonists as potential therapeutics for chronic pain.
Learn More >Diabetic polyneuropathy (DPN) is the most common complication in diabetes and can be painful in up to 26% of all diabetic patients. Peripheral nerves are shielded by the blood-nerve barrier (BNB) consisting of the perineurium and endoneurial vessels. So far, there are conflicting results regarding the role and function of the BNB in the pathophysiology of DPN. In this study, we analyzed the spatiotemporal tight junction protein profile, barrier permeability, and vessel-associated macrophages in Wistar rats with streptozotocin-induced DPN. In these rats, mechanical hypersensitivity developed after 2 weeks and loss of motor function after 8 weeks, while the BNB and the blood-DRG barrier were leakier for small, but not for large molecules after 8 weeks only. The blood-spinal cord barrier remained sealed throughout the observation period. No gross changes in tight junction protein or cytokine expression were observed in all barriers to blood. However, expression of Cldn1 mRNA in perineurium was specifically downregulated in conjunction with weaker vessel-associated macrophage shielding of the BNB. Our results underline the role of specific tight junction proteins and BNB breakdown in DPN maintenance and differentiate DPN from traumatic nerve injury. Targeting claudins and sealing the BNB could stabilize pain and prevent further nerve damage. KEY MESSAGES: • In diabetic painful neuropathy in rats: • Blood nerve barrier and blood DRG barrier are leaky for micromolecules. • Perineurial Cldn1 sealing the blood nerve barrier is specifically downregulated. • Endoneurial vessel-associated macrophages are also decreased. • These changes occur after onset of hyperalgesia thereby maintaining rather than inducing pain.
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