The journal of pain : official journal of the American Pain Society
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Sickle cell disease (SCD) is associated with episodes of severe vaso-occlusive pain beginning in infancy with a subset of patients with SCD transitioning to chronic pain. Response to experimental pain using quantitative sensory testing in these patients suggests altered pain processing. The objectives of this study were to characterize sensitivity to multiple modalities of experimental pain stimuli and to interrogate the relationship of psychological covariates, clinical pain burden, and pain-related outcomes to experimental pain sensitivity in children with SCD compared with healthy individuals of similar age and sex. ⋯ Anxiety, depressive symptoms, catastrophizing, and somatization were found to be associated with increased sensitivity to experimental pain stimuli. Increased frequency of painful episodes in SCD was associated with decreased sensitivity to heat pain and decreased mechanical temporal summation. These data suggest that careful consideration be given to psychological factors, age, sex, and clinical burden of pain when studying response to experimental pain in SCD.
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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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This study aimed to describe utilization of opioid medications among infants, children, and adolescents on the inpatient setting. These data are needed to guide clinical trials and improve research methodologies, as well as to inform more about possible sources of opioid misuse in the United States. A retrospective chart review was conducted covering a span of 1 year, with a special focus on the prescription of opioids for long-term treatment of chronic pain. ⋯ Among those who were prescribed opioids for >14 days, the focus was often for reasons other than pain. These data indicate that models of chronic pain that may be utilized in clinical trials of longer-term opioid usage in pediatrics are exceedingly limited. In addition, the patterns of utilization indicate that opioid administration among pediatric inpatients is not a likely contributory factor to concerns about opioid misuse in the United States.
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A growing body of research has identified fear of visceral sensations as a potential mechanism in the development and maintenance of visceral pain disorders. However, the extent to which such learned fear affects visceroception remains unclear. To address this question, we used a differential fear conditioning paradigm with nonpainful esophageal balloon distensions of 2 different intensities as conditioning stimuli (CSs). ⋯ Analyses of galvanic skin and startle eyeblink responses as physiological markers of successful conditioning showed increased fear responses to the CS+ compared with the CS-, but only in the group with the low-intensity stimulus as CS+. Computational modeling of response times and response accuracies revealed that differential fear learning affected perceptual decision-making about the intensities of visceral sensations such that sensations were more likely to be categorized as more intense. These results suggest that associative learning might indeed contribute to visceral hypersensitivity in functional gastrointestinal disorders.
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Emotional, motivational, and interpersonal dimensions are considered integral to pain experience but have largely been examined separately. In this focus article, we argue that an integrative theoretical account that acknowledges each of these elements is a critical next step to capture the complexity and nuance of interpersonal pain dynamics and to shape future research. The aim of this focus article is to provide a foundation for such an account by drawing upon established insights from appraisal theory of emotion, influential behavioral models, empathy/interpersonal pain research, and social psychology literature to highlight conceptual relationships, potential mechanisms of action, and avenues of inquiry that have not previously been examined in the context of pain. ⋯ We discuss an affective-motivational tension between self- and other-oriented goals that can arise within the interpersonal pain context, and how such dynamics may affect the nature and effectiveness of caregiving behavior. We then describe the role of emotion regulation and strategies that may facilitate optimal interpersonal pain dynamics and caregiving within a multiple goal context. Finally, we outline a foundation for an integrative theoretical model and directions for future research.