The journal of pain : official journal of the American Pain Society
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The use of rodents in preclinical studies has contributed greatly to our understanding of the pathophysiology of chronic neuropathic pain. These animal models are limited because of their poor clinical translation. We developed a pig model for chronic pain caused by surgically induced peripheral neuritis trauma (PNT). Seventy-five percent of the animals exhibited mechanical and tactile allodynia, which are indicative of painful neuropathy, by day 28 after surgery. Importantly, the PNT-injured pigs retained their ability to walk or to stand on their injured leg. Messenger RNA analysis of acute inflammatory cytokines calcitonin gene-related peptide and brain-derived neurotrophic factor at the site of injury suggests transient inflammation followed by a persistent high level of neurologic markers. Gabapentin and morphine effectively inhibited hypersensitivity to von Frey filaments and to feather stimuli, and reversed spontaneous pain-related behavior in a dose-related manner. No analgesic effect was detected in PNT-injured pigs after treatment with aprepitant, similar to observations in humans and contrary to observations in rodents. In conclusion, PNT-induced trauma in pigs may comprise a valid preclinical model for the study of the chronification of peripheral nerve injury and for the study of new pain therapies. ⋯ This article presents the characterization of a new peripheral neuritis trauma (PNT) model in pigs. The pig PNT model could help close the translational gap between preclinical and clinical responses and may contribute to improved efficacy or safety of candidate drugs.
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Chronic back pain (CBP) is associated with circumscribed atrophy in gray matter (GM) predominantly localized in areas of the so-called pain matrix and the prefrontal cortex (PFC). Previous studies applying voxel-based morphometry (VBM) for identifying structural brain alterations related to CBP have reported inconsistent results, were limited to small sample sizes, and often did not control for medication. We therefore used VBM for high-resolution magnetic resonance images to investigate the association of CBP and regional GM volume in 111 individuals with CBP and 432 pain-free controls derived from the representative Study of Health in Pomerania, controlling for effects of medication. CBP was associated with decreased regional GM in the ventrolateral PFC and dorsolateral PFC, both the ventral and dorsal medial PFC, and the anterior insula. Pain intensity showed a weak negative correlation with GM volume in the left dorsolateral PFC, ventrolateral PFC, and anterior cingulate cortex. The CBP sample showed alterations in regions commonly associated with pain processing and emotional demands. To our knowledge, this is the first VBM study reporting decreased regional GM volume in the medial PFC in a CBP sample. We were unable to confirm alterations in regions other than the dorsolateral PFC and the insula. ⋯ Previous studies reported inconsistent results for brain areas altered in chronic pain conditions, which may be in part attributable to small sample sizes, medication use, or emotional comorbidities. This study in a large and representative cohort helps to clarify these issues.
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Daily pain-related attributions for and negative affective reactions to the nonpursuit of work goals and individual differences in chronic pain severity and stress were used to predict work goal resumption in a sample of 131 adults with chronic pain. Variables were assessed via questionnaires and a 21-day diary. On days when participants reported nonpursuit of work goals in the afternoon, increases in pain-related attributions for goal interruption were positively associated with higher negative affective reactions which, in turn, were associated with an increased likelihood of same-day work goal resumption. Stress amplified the relation between pain-related attributions and negative affective reactions, and chronic pain severity was positively related to work goal resumption. ⋯ Under certain circumstances, chronic pain and pain-related attributions can have positive motivational effects on work goal resumption. The findings of the present study may contribute to the development of interruption management techniques in vocational settings that leverage the roles of pain-related attributions, goal cognition, and emotionality.
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It has long been known that the bedding type on which animals are housed can affect breeding behavior and cage environment, yet little is known about its effects on evoked behavior responses or nonreflexive behaviors. C57BL/6 mice were housed for 2 weeks on 1 of 5 bedding types: aspen Sani-Chips (standard bedding for our institute), ALPHA-Dri, Cellu-Dri, Pure-o'Cel, or TEK-Fresh. Mice housed on aspen exhibited the lowest (most sensitive) mechanical thresholds and those on TEK-Fresh exhibited 3-fold higher thresholds. Although bedding type had no effect on responses to punctate or dynamic light touch stimuli, TEK-Fresh-housed animals exhibited greater responsiveness in a noxious needle assay than did those housed on the other bedding types. Heat sensitivity was also affected by bedding because animals housed on aspen exhibited the shortest (most sensitive) latencies to withdrawal, whereas those housed on TEK-Fresh had the longest (least sensitive) latencies to response. Slight differences between bedding types were also seen in a moderate cold temperature preference assay. A modified tactile conditioned place preference chamber assay revealed that animals preferred TEK-Fresh to aspen bedding. Bedding type had no effect in a nonreflexive wheel running assay. In both acute (2 day) and chronic (5 week) inflammation induced by injection of complete Freund's adjuvant in the hindpaw, mechanical thresholds were reduced in all groups regardless of bedding type, but TEK-Fresh and Pure-o'Cel groups exhibited a greater dynamic range between controls and inflamed cohorts than aspen-housed mice. ⋯ These findings indicate that the bedding type routinely used to house animals can markedly affect the dynamic range of mechanical and heat behavior assays under normal and tissue injury conditions. Among beddings tested, TEK-Fresh bedding resulted in the least sensitive baseline thresholds for mechanical and thermal stimuli and the greatest dynamic range after tissue injury. Therefore, selection of routine cage bedding material should be carefully considered for animals that will be tested in behavioral somatosensory assays.