The journal of pain : official journal of the American Pain Society
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Observational Study
Multivariable modeling of phenotypic risk factors for first-onset TMD: the OPPERA prospective cohort study.
Incidence of temporomandibular disorder (TMD) was predicted with multivariable models that used putative risk factors collected from initially TMD-free individuals in the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study. The 202 baseline risk factors included sociodemographic and clinical characteristics, measures of general health status, experimental pain sensitivity, autonomic function, and psychological distress. Study participants (n = 2,737) were then followed prospectively for a median of 2.8 years to ascertain cases of first-onset TMD. Lasso regression and random forest models were used to predict incidence of first-onset TMD using all of the aforementioned measures. Variable importance scores identified the most important risk factors, and their relationship with TMD incidence was illustrated graphically using partial dependence plots. Two of the most important risk factors for elevated TMD incidence were greater numbers of comorbid pain conditions and greater extent of nonspecific orofacial symptoms. Other important baseline risk factors were preexisting bodily pain, heightened somatic awareness, and greater extent of pain in response to examiners' palpation of the head, neck, and body. Several demographic variables persisted as risk factors even after adjusting for other OPPERA variables, suggesting that environmental variables not measured in OPPERA may also contribute to first-onset TMD. ⋯ Multivariable methods were used to identify the most important predictors of first-onset TMD in the OPPERA study. Important variables included comorbid pain conditions, preexisting pain, and somatic awareness. Demographic characteristics, which probably reflect environmental variables not measured in OPPERA, also appear to play an important role in the etiology of TMD.
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Previous studies have reported that the intrathecal (i.t.) administration of transforming growth factor β1 (TGF-β1) prevents and reverses neuropathic pain. However, only limited information is available regarding the possible role and effects of spinal TGF-β1 in neuropathic pain. We aimed to investigate the antinociceptive effects of exogenous TGF-β1 on chronic constriction injury (CCI)-induced neuropathic pain in rats. We demonstrated that sciatic nerve injury caused a downregulation of endogenous TGF-β1 levels on the ipsilateral side of the lumbar spinal dorsal gray matter, and that the i.t. administration of TGF-β1 (.01-10 ng) significantly attenuated CCI-induced thermal hyperalgesia in neuropathic rats. TGF-β1 significantly inhibited CCI-induced spinal neuroinflammation, microglial and astrocytic activation, and upregulation of tumor necrosis factor-α. Moreover, i.t. TGF-β1 significantly attenuated the CCI-induced downregulation of glutamate transporter 1, the glutamate aspartate transporter, and the excitatory amino acid carrier 1 on the ipsilateral side. Furthermore, i.t. TGF-β1 significantly decreased the concentrations of 2 excitatory amino acids, aspartate and glutamate, in the spinal dialysates in CCI rats. In summary, we conclude that the mechanisms of the antinociceptive effects of i.t. TGF-β1 in neuropathy may include attenuation of spinal neuroinflammation, attenuation, or upregulation of glutamate transporter downregulation, and a decrease of spinal extracellular excitatory amino acids. ⋯ Clinically, medical treatment is usually initiated after the onset of intractable pain. Therefore, in the present study, i.t. TGF-β1 was designed to be administered 2 weeks after the establishment of CCI pain. Compared to the continuous TGF-β1 infusion mode, single-dose administration seems more convenient and practical to use.
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Chronic pain resulting from physical stressors is often accompanied by psychological disorders such as depression. Although depressive disorders are associated with changes in brain anatomy, it remains unknown if changes in brain anatomy associated with increased state depression levels also occur in patients with chronic pain. When individuals are experiencing physical stressors such as ongoing pain, depressive personality traits may predispose them to develop depressive states. The aim of this study was to use brain morphometry to determine the interaction among chronic pain, state and trait depression, and regional brain structure. We investigated regional gray matter volume in 42 chronic pain patients and 35 controls using voxel-based morphometry of T1-weighted anatomical images. Significant relationships between regional gray matter volume and state or trait depressive values were determined. In chronic pain patients, state depression scores were significantly correlated to subtle changes in the thalamus and the cingulate, dorsolateral prefrontal, and hippocampal cortices. These same brain regions were also significantly correlated to trait depressive scores. Unexpectedly, gray matter volumes in these regions were not correlated to trait depressive scores in healthy controls. Because trait depressive values were not correlated to gray matter in controls, but were so in chronic pain patients, these data strongly suggest that subtle changes in brain anatomy can evoke changes in individuals' trait depression values. If these regional gray matter changes are severe enough, changes in an individual's personality trait may result. ⋯ This study demonstrates anatomical brain alterations associated with both state and trait depression in chronic pain patients. Because our study reveals that trait depression is not correlated to the anatomy of these regions in healthy controls, ongoing pain itself may result in anatomical changes that in turn can alter an individual's personality.
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The pain medication OxyContin (hereafter referred to as oxycodone extended release) has been the subject of sustained, and largely negative, media attention in recent years. We sought to determine whether media coverage of oxycodone extended release in North American newspapers has led to changes in prescribing of the drug in Nova Scotia, Canada. An interrupted time-series design examined the effect of media attention on physicians' monthly prescribing of opioids. The outcome measures were, for each physician, the monthly proportions of all opioids prescribed and the proportion of strong opioids prescribed that were for oxycodone extended release. The exposure of interest was media attention defined as the number of articles published each month in 27 North American newspapers. Variations in media effects by provider characteristics (specialty, prescribing volume, and region) were assessed. Within-provider changes in the prescribing of oxycodone extended release in Nova Scotia were observed, and they followed changes in media coverage. Oxycodone extended release prescribing rose steadily prior to receiving media attention. Following peak media attention in the United States, the prescribing of oxycodone extended release slowed. Likewise, following peak coverage in Canadian newspapers, the prescribing of oxycodone extended release declined. These patterns were observed across prescriber specialties and by prescriber volume, though the magnitude of change in prescribing varied. ⋯ This study demonstrates that print media reporting of oxycodone extended release in North American newspapers, and its continued portrayal as a social problem, coincided with reductions in the prescribing of oxycodone extended release by physicians in Nova Scotia.
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The ventrolateral periaqueductal gray (vlPAG) contributes to morphine antinociception and tolerance. Chronic inflammatory pain causes changes within the PAG that are expected to enhance morphine tolerance. This hypothesis was tested by assessing antinociception and tolerance following repeated microinjections of morphine into the vlPAG of rats with chronic inflammatory pain. Microinjection of morphine into the vlPAG reversed the allodynia caused by intraplantar administration of complete Freund's adjuvant and produced antinociception on the hot plate test. Although there was a gradual decrease in morphine antinociception with repeated testing, there was no evidence of tolerance when morphine- and saline-treated rats with hind paw inflammation were tested with cumulative doses of morphine. In contrast, repeated morphine injections into the vlPAG caused a rightward shift in the morphine dose-response curve in rats without hind paw inflammation, as would be expected with the development of tolerance. The lack of tolerance in complete Freund's adjuvant-treated rats was evident whether rats were exposed to repeated behavioral testing or not (experiment 2) and whether they were treated with 4 or 8 prior microinjections of morphine into the vlPAG (experiment 3). These data demonstrate that chronic inflammatory pain does not disrupt the antinociceptive effect of microinjecting morphine into the vlPAG, but it does disrupt the development of tolerance. ⋯ The present data show that induction of chronic inflammatory pain does not disrupt the antinociceptive effect of microinjecting morphine into the vlPAG, but it does attenuate the development of tolerance. This finding indicates that tolerance to opioids in rats with inflammatory pain is mediated by structures other than the vlPAG.