Pain
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Randomized Controlled Trial
Trajectories of Change During a Randomized Controlled Trial of Internet-delivered Psychological Treatment for Adolescent Chronic Pain: How does Change in Pain and Function Relate?
Although pain and function improve at immediate posttreatment for youth receiving cognitive behavioral therapy for chronic pain, limited data are available to understand changes that youth make during psychological treatment. We sought to characterize distinct trajectory patterns of change in pain and function to understand the temporal association of these changes during internet-delivered cognitive behavioral therapy (CBT). Weekly repeated assessments of pain and function were conducted during 8 weeks of treatment among 135 adolescents, aged 11 to 17 years, with chronic pain who were randomized to the cognitive behavioral intervention arm of an ongoing trial of internet-delivered CBT (Web-based management of adolescent pain; Web-MAP2). ⋯ There was no support for improvements in either pain or function to precede changes in the other domain. Findings may be useful in informing future studies of psychosocial treatments for pediatric chronic pain to consider how to target treatment strategies to distinct patient response profiles. This may lead to the development of intervention strategies that can both more effectively target children's pain and function during treatment and lead to sustained changes after treatment.
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Randomized Controlled Trial
GABAergic modulation in central sensitization in humans: a randomized placebo-controlled pharmacokinetic-pharmacodynamic study comparing clobazam with clonazepam in healthy volunteers.
Positive allosteric modulators of GABAA receptors (GAMs) acting at specific subtypes of GABAA receptors effectively restore compromised spinal pain control in rodents. Studies addressing a similar antihyperalgesic effect in humans are sparse and are hampered by sedative effects of nonselective GAMs available for use in humans. We present results from a randomized controlled double-blind crossover study in 25 healthy volunteers, which addressed potential antihyperalgesic actions of clobazam (CBZ) and clonazepam (CLN) at mildly sedating equianticonvulsive doses. ⋯ Active compounds induced stronger sedation than placebo, but these differences disappeared 8 hours after drug application. We demonstrate here that GAMs effectively reduce central sensitization in healthy volunteers. These results provide proof-of-principle evidence supporting efficacy of GAMs as antihyperalgesic agents in humans and should stimulate further research on compounds with improved subtype specificity.
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Randomized Controlled Trial
A new objective method for acquisition and quantification of reflex receptive fields.
The nociceptive withdrawal reflex (NWR) is a polysynaptic spinal reflex correlated with pain perception. Assessment of this objective physiological measure constitutes the core of existing methods for quantification of reflex receptive fields (RRFs), which however still suffer from a certain degree of subjective involvement. This article proposes a strictly objective methodology for RRF quantification based on automated identification of NWR thresholds (NWR-Ts). ⋯ The NWR-T-based quantifications required a smaller sample size than any of the existing RRF measures to detect a clinically relevant effect in a crossover study design involving more than 1 session. Of all measures, quantification from mapping of inversed NWR-Ts demonstrated superior reliability both within (CR, 0.25) and between sessions (CR, 0.28). The study presents a more reliable and robust quantification of the RRF to be used as biomarker of pain hypersensitivity in clinical and experimental research.
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Randomized Controlled Trial
Spinal cord stimulation attenuates temporal summation in patients with neuropathic pain.
Evidence has shown that electrical stimulation at the dorsal columns attenuated the "wind-up" phenomenon in dorsal horn neurons in nerve-injured rats. This study was aimed to test the effect of spinal cord stimulation (SCS) on temporal summation (TS), the clinical correlate of the wind-up phenomenon in patients with radicular leg pain. Eighteen patients with SCS implants were tested both 30 minutes after SCS activation ("ON") and 2 hours after turning it off ("OFF"), in a random order. ⋯ In the nonpainful leg, SCS activation failed to produce an effect on TS (24 ± 20 vs 21 ± 24 in SCS "OFF" and "ON", respectively; P = 0.277). In contrast, a significant decrease in the magnitude of TS in the affected leg was observed in response to SCS activation (from 32 ± 33 to 19 ± 24; P = 0.017). These results suggest that attenuation of TS, which likely represents suppression of hyperexcitability in spinal cord neurons, is a possible mechanism underlying SCS analgesia in patients with neuropathic pain.
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Randomized Controlled Trial
Differential neurophysiological correlates of bottom-up and top-down modulations of pain.
The perception of pain is highly variable. It depends on bottom-up-mediated factors like stimulus intensity and top-down-mediated factors like expectations. In the brain, pain is associated with a complex pattern of neuronal responses including evoked potentials and induced responses at alpha and gamma frequencies. ⋯ In contrast, placebo analgesia was associated with changes of evoked potentials, but not of alpha and gamma responses. These findings reveal that pain-related neuronal responses are differentially sensitive to bottom-up and top-down modulations of pain, indicating that they provide complementary information about pain perception. The results further show that pain-induced gamma oscillations do not invariably encode pain perception but may rather represent a marker of sensory processing whose influence on pain perception varies with behavioral context.