The journal of pain : official journal of the American Pain Society
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Use of multiple pharmacies concurrently (pharmacy shopping) and overlapping prescriptions may be indicators of potential misuse or abuse of prescription opioid medications. To evaluate strategies for identifying patients at high risk, we first compared different definitions of pharmacy shopping and then added the indicator of overlapping opioid prescriptions. We identified a cohort of 90,010 Medicaid enrollees who used ≥ 3 opioid prescriptions for ≥ 90 days during 2008 to 2010 from a multistate Medicaid claims database. We compared the diagnostic odds ratios for opioid overdose events of 9 pharmacy shopping definitions. Within a 90-day interval, a threshold of 4 pharmacies had the highest diagnostic odds ratio and was used to define pharmacy shopping. The overdose rate was higher in the subgroup with overlapping prescriptions (18.5 per 1,000 person-years [PYs]) than in the subgroup with pharmacy shopping as the sole indicator (10.7 per 1,000 PYs). Among the subgroup with both conditions, the overdose rate was 26.3 per 1,000 PYs, compared with 4.3 per 1,000 PYs for those with neither condition. Overlapping opioid prescriptions and pharmacy shopping measures had adjusted hazard ratios of 3.0 and 1.8, respectively, for opioid overdose. Using these measures will improve accurate identification of patients at highest risk of opioid overdose, the first step in implementing targeted prevention policies. ⋯ Long-term prescription opioid use may lead to adverse events, including overdose. Both pharmacy shopping and overlapping opioid prescriptions are associated with adverse outcomes. This study demonstrates that using both indicators will better identify those at high risk of overdose.
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Descending pain inhibition is an endogenous pain control system thought to depend partially on the activation of bulbospinal monoaminergic pathways. Deficits in descending pain inhibition have been reported in numerous human chronic pain conditions, but there is currently no consensus regarding the neurochemical correlates responsible for this deficit. The aims of this study were to 1) assess the efficacy of descending pain inhibition in pain-free and chronic pain subjects, 2) screen for changes in centrally (ie, cerebrospinal fluid) and peripherally (ie, plasma) acting monoamine concentrations, and 3) explore the relationship between descending pain inhibition and monoamine neurotransmitter concentrations. Our results clearly show a deficit in pain inhibition, along with lower plasma norepinephrine and metanephrine concentrations in chronic pain subjects, compared to pain-free subjects. No differences were found in cerebrospinal fluid neurotransmitter concentrations. Finally, our results revealed a positive relationship between blood-bound norepinephrine and metanephrine concentrations and the efficacy of descending pain inhibition. Thus, basal monoamine levels in blood were related to descending pain inhibition. This finding supports the emerging idea that individual differences in descending pain inhibition may be linked to individual differences in peripheral processes, such as monoamines release in blood, which are possibly related to cardiovascular control. ⋯ This article presents psychophysical and neurochemical findings that indicate that the latent potential of descending pain inhibitory responses is associated with differential activity in peripheral processes governed by monoamine neurotransmitter release, bringing insights into the relationship between descending pain inhibition and cardiovascular control in humans.
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The reliability of quantitative sensory testing (QST) is affected by the error attributable to both test occasion and rater (examiner) and the interactions between them. Most reliability studies account for only 1 source of error. The present study employed a fully crossed, multivariate generalizability design to account for rater and occasion variance simultaneously. Nineteen healthy volunteers were examined with a battery of 7 QST procedures 4 times on 2 occasions by 2 raters. The QST battery was composed to include a mix of different pain stimuli and response domains, including threshold, intensity, tolerance, and modulation with mechanical, thermal, and chemical stimuli. The classical test-retest and interrater reliability (.19 < intraclass correlation coefficient <.92) was in line with the literature, and generalizability analysis indicated that the universe score was generally the dominant source of variation (relative contribution = 19%, 78%). Error attributable to the interaction between study participant and occasion was also influential. Dependability coefficients indicated that a substantial increase in reliability and feasibility could be achieved by employing a composite QST battery compared to single QST procedures. Reliability was improved more by repeated testing on separate occasions than by repeated testing by different raters. ⋯ When balancing reliability and feasibility, the current findings suggest that a carefully selected battery of QST procedures repeated on a few occasions may be optimal.
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Social communication deficits and repetitive behaviors are established characteristics of autism spectrum disorder (ASD) and the focus of considerable study. Alterations in pain sensitivity have been widely noted clinically but remain understudied and poorly understood. The ASD population may be at greater risk for having their pain undermanaged, especially in children with impaired cognitive ability and limited language skills, which may affect their ability to express pain. Given that sensitivity to noxious stimuli in adolescents with ASD has not been systematically assessed, here we measured warm and cool detection thresholds and heat and cold pain thresholds in 20 high-functioning adolescents with ASD and 55 typically developing adolescents using a method-of-limits quantitative sensory testing protocol. Adolescents with ASD had a loss of sensory function for thermal detection (P < .001, both warm and cool detection thresholds) but not pain threshold (P > .05, both heat and cold pain thresholds) in comparison to controls, with no evidence for significant age or sex effects (P > .05). Intelligence quotients and symptomatology were significantly correlated with a loss of some types of thermal perception in the ASD population (ie, warm detection threshold, cool detection threshold, and heat pain threshold; P < .05). Decreased thermal sensitivity in adolescents with ASD may be associated with cognitive impairments relating to attentional deficits. Our findings are consistent with previous literature indicating an association between thermal perception and cortical thickness in brain regions involved in somatosensation, cognition, and salience detection. Further brain-imaging research is needed to determine the neural mechanisms underlying thermal perceptual deficits in adolescents with ASD. ⋯ We report quantitative evidence for altered thermal thresholds in adolescents with ASD. Reduced sensitivity to warmth, coolness, and heat pain was related to impaired cognitive ability. Caregivers and clinicians should consider cognitive ability when assessing and managing pain in adolescents with ASD.
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Acute postoperative pain remains a significant health care issue. Development of anatomically relevant animal models of postoperative pain, with improved predictive validity, would advance understanding of postoperative pain mechanisms and improve treatment outcomes. This study aimed to develop, characterize, and validate a rat model of acute postoperative pain associated with inguinal hernia repair based on the Lichtenstein inguinal hernia repair procedure (without hernia induction). We hypothesized that the surgery would result in reduced spontaneous locomotor activity, which would represent a pain-related phenotype. Postsurgical characterization involved extensive monitoring of home cage and open field locomotor activity, as well as mechanical hypersensitivity and assessment of c-Fos expression in the dorsal horn of the spinal cord. In pharmacologic validation studies, rats received morphine, carprofen, or paracetamol 1 hour before, and/or immediately after, surgery. Rats that underwent hernia repair surgery exhibited significantly lower horizontal and vertical activities in the home cage and open field in the early postsurgical period, compared with sham rats or rats that underwent skin incision only. Morphine, carprofen, and paracetamol attenuated the surgery-induced reductions in locomotor activity, to varying degrees. Surgery was associated with significantly increased c-Fos expression in the ipsilateral dorsal horn of the spinal cord, an effect attenuated by carprofen treatment. These results support the development and characterization of a novel, anatomically relevant animal model of acute postoperative pain that may facilitate development of improved treatment regimens. ⋯ Acute pain following inguinal hernia repair can be difficult to treat. Here we report, for the first time, the development of a novel, anatomically relevant rat model to facilitate improved understanding and treatment of acute postoperative pain following inguinal hernia repair.