The journal of pain : official journal of the American Pain Society
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Intervertebral disc degeneration (DD) is a cause of low back pain (LBP) in some individuals. However, although >30% of adults have DD, LBP only develops in a subset of individuals. To gain insight into the mechanisms underlying nonpainful versus painful DD, human cerebrospinal fluid (CSF) was examined using differential expression shotgun proteomic techniques comparing healthy control participants, subjects with nonpainful DD, and patients with painful DD scheduled for spinal fusion surgery. ⋯ Cystatin C and hemopexin were selected for further examination using enzyme-linked immunosorbent assay in a larger cohort. While cystatin C correlated with DD severity but not pain or disability, hemopexin correlated with pain intensity, physical disability, and DD severity. This study shows that CSF can be used to study mechanisms underlying painful DD in humans, and suggests that while painful DD is associated with nerve injury, inflammation itself is not sufficient to develop LBP.
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Upon systemic administration in rats, the prodrug L-4-chlorokynurenine (4-Cl-KYN; AV-101; VistaGen Therapeutics, Inc, South San Francisco, CA) is rapidly absorbed, actively transported across the blood-brain barrier, and converted in astrocytes to 7-chlorokynurenic acid (7-Cl-KYNA), a potent and specific antagonist of the glycine B coagonist site of the N-methyl-D-aspartate (NMDA) receptor. We examined the effects of 4-Cl-KYN in several rat models of hyperalgesia and allodynia and determined the concentrations of 4-Cl-KYN and newly produced 7-Cl-KYNA in serum, brain, and spinal cord. ⋯ Our conclusions show that after systemic delivery, the highest 2 doses (167 and 500 mg/kg) of 4-Cl-KYN yielded brain concentrations of 7-Cl-KYNA exceeding its half maximal inhibitory concentration (IC50) at the glycine B site and resulted in dose-dependent antihyperalgesia in the 4 models of facilitated processing associated with tissue inflammation and nerve injury. On the basis of the relative dose requirements for analgesic actions and side effect profiles from these experiments, 4-Cl-KYN is predicted to have antihyperalgesic efficacy and a therapeutic ratio equal to gabapentin and superior to MK-801.
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Half of children admitted after surgery experience intense pain in hospital, and many experience continued pain and delayed functional recovery at home. However, there is a gap in tools available to measure acute functional ability in pediatric postsurgical settings. We aimed to validate the Youth Acute Pain Functional Ability Questionnaire (YAPFAQ) in a large inpatient pediatric surgical population, evaluate its responsiveness to expected functional recovery, and develop a short form for broad clinical implementation. The YAPFAQ is a self-report measure assessing acute functional ability, developed in children admitted for acute sickle cell pain. We evaluated psychometric properties of the measure in 564 children ages 8 to 18 years admitted after surgery. A sample of 54 participants completed the YAPFAQ daily for 3 days after major surgery to assess responsiveness. The measure showed good reliability (Cronbach α = .96) and construct validity, with expected relationships with physical health-related quality of life (r = -.53, P < .001) and pain intensity (r = .42, P < .001). YAPFAQ scores decreased over time showing good responsiveness to expected recovery. A 3-item short form of the YAPFAQ showed promising psychometric properties. Early assessment of functioning after surgery may identify children at risk for poor functional outcomes and allow targeting of therapies to improve postsurgical recovery. ⋯ The YAPFAQ showed promising psychometric properties in a pediatric postsurgical population. This study addresses a gap in tools available to monitor functional recovery during hospitalization after pediatric surgery. Early detection of problems with recovery may enable targeted therapies to improve postsurgical outcomes.
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There is increasing evidence that contextual forms of cognitive-behavioral therapy (CBT) are effective in the management of chronic pain, yet little is understood about the factors that moderate or predict outcomes in these treatments. This systematic review aimed to identify pretreatment participant characteristics associated with positive treatment responses in contextual CBT for chronic pain. Medline, EMBASE, PsychINFO, and CENTRAL were searched to identify eligible studies. Studies were included if the participants were adults with chronic pain, designs were longitudinal, treatments focused on psychological flexibility or mindfulness, and reported results allowed for examination of moderators or predictors of standard treatment outcomes. Of 991 records initially identified, 20 were eligible for inclusion in the review. Some evidence suggested that baseline emotional functioning predicts treatment response, but the direction of this association varied between studies. Substantive findings were inconsistent and inconclusive, however, methodological limitations were consistent. These included treatment heterogeneity, and a lack of theoretical, a priori guidance in examining potential predictors. Future research should adopt a theoretically based approach to examining moderators in relation to specific treatment methods and therapeutic processes. Considering moderation without first considering mediation is probably a limited strategy. ⋯ In this systematic review we examined evidence for potential predictors or moderators of outcomes in contextual CBT for chronic pain. Substantive findings were inconclusive but important methodological limitations and a lack of theoretical guidance were found. Future research should explicitly plan relevant methods and follow clear theoretical models.
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Parents play an important role in supporting school functioning in youth with chronic pain, but no validated tools exists to assess parental responses to child and adolescent pain behaviors in the school context. Such a tool would be useful in identifying targets of change to reduce pain-related school impairment. The goal of this study was to develop and preliminarily validate the Parent Responses to School Functioning Questionnaire (PRSF), a parent self-report measure of this construct. ⋯ Criterion validity was demonstrated by significant correlations with school absence rates and overall school functioning, and construct validity was demonstrated by correlations with general parental responses to pain. Three subscales emerged capturing parents' personal distress, parents' level of distrust of the school, and parents' expectations and behaviors related to their child's management of challenging school situations. These results provide preliminary support for the PRSF as a psychometrically sound tool to assess parents' responses to child pain in the school setting.