The journal of pain : official journal of the American Pain Society
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The effects of minocycline or riluzole treatment on spinal root avulsion-induced pain in adult rats.
Spinal root avulsion produces tactile and thermal hypersensitivity, neurodegeneration, and microglial and astrocyte activation in both the deafferented and the adjacent intact spinal cord segments. Following avulsion of the fifth lumbar spinal root, immediate and prolonged treatment with riluzole or minocycline for 2 weeks altered the development of behavioral hypersensitivity. Riluzole delayed the onset of thermal and tactile hypersensitivity and partially reversed established pain behavior. Minocycline effectively prevented and reversed both types of behavioral change. Histologic analysis revealed that both drugs reduced microglial staining in the spinal cord, with minocycline being more effective than riluzole. Astrocyte activation was ameliorated to a lesser extent. Surprisingly, neither drug provided a neuroprotective effect on avulsed motoneurons. ⋯ Immediate treatment of spinal root avulsion injuries with minocycline or riluzole prevents the onset of evoked pain hypersensitivity by reducing microglial cell activation. When treatment is delayed, minocycline, but not riluzole, reverses pre-established hypersensitivity. Thus, these drugs may provide a new translational treatment option for chronic avulsion injury pain.
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Review Meta Analysis
Associations between pain appraisals and pain outcomes: meta-analyses of laboratory pain and chronic pain literatures.
In this research, meta-analyses were performed to evaluate associations between primary appraisals of pain as a source of threat and/or challenge and responses to 1) noxious laboratory stimuli and 2) chronic noncancer pain. Twenty-two laboratory pain studies comprising 2,031 participants and 59 chronic pain studies based on 9,135 patients were identified for analysis. For laboratory pain, elevated threat appraisals were linked to overall increases in reported pain, reduced pain tolerance, and high levels of passive coping. Method of measuring appraisal as well as type and duration of noxious stimulation moderated some of these associations. Challenge appraisals were related to more pain tolerance and less passive coping but not pain intensity. For chronic pain studies, threat appraisals had positive overall correlations with pain intensity, impairment, affective distress, and passive coping but were negatively related to active coping. The pattern of associations between challenge appraisals and outcomes was largely complementary. Appraisal scale used and gender were consistent moderators of appraisal-outcome relations in chronic pain samples. In sum, appraisals of pain as a source of potential damage or opportunity have robust associations with responses to acute laboratory pain and ongoing chronic pain. ⋯ Meta-analyses evaluated associations between primary appraisals and responses to laboratory pain and chronic pain. Significant effect sizes for most outcomes suggest that appraisals of pain as a source of threat and challenge have important implications for functioning in response to pain.
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Despite rapidly increasing intervention, functional disability due to chronic low back pain (cLBP) has increased in recent decades. We often cannot identify mechanisms to explain the major negative impact cLBP has on patients' lives. Such cLBP is often termed non-specific and may be due to multiple biologic and behavioral etiologies. Researchers use varied inclusion criteria, definitions, baseline assessments, and outcome measures, which impede comparisons and consensus. Therefore, NIH Pain Consortium charged a Research Task Force (RTF) to draft standards for research on cLBP. The resulting multidisciplinary panel recommended using 2 questions to define cLBP; classifying cLBP by its impact (defined by pain intensity, pain interference, and physical function); use of a minimum dataset to describe research participants (drawing heavily on the PROMIS methodology); reporting "responder analyses" in addition to mean outcome scores; and suggestions for future research and dissemination. The Pain Consortium has approved the recommendations, which investigators should incorporate into NIH grant proposals. The RTF believes that these recommendations will advance the field, help to resolve controversies, and facilitate future research addressing the genomic, neurologic, and other mechanistic substrates of chronic low back pain. We expect that the RTF recommendations will become a dynamic document and undergo continual improvement. ⋯ A task force was convened by the NIH Pain Consortium with the goal of developing research standards for chronic low back pain. The results included recommendations for definitions, a minimum dataset, reporting outcomes, and future research. Greater consistency in reporting should facilitate comparisons among studies and the development of phenotypes.
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From a treatment perspective, it is highly relevant to pinpoint individual vulnerability factors for resistance to exposure treatment in highly fearful chronic pain patients. Previous fear conditioning research showed that healthy individuals scoring relatively high on trait anxiety display sustained fear to safety cues during extinction. In the context of fear of movement-related pain, this intriguing question has been largely neglected so far. Even more importantly, positive psychological traits such as trait positive affect may function as protective factors against the spreading of fear to safe movements and improve exposure treatment outcomes. In this study, healthy participants completed a trait anxiety and trait positive affect questionnaire and underwent acquisition and extinction of fear of movement-related pain using an experimental voluntary movement paradigm. During acquisition, one movement (CS+) was paired with a painful stimulus and another movement was not (CS-). During extinction, the CS+ was no longer reinforced. Results show failure of fear inhibition to the CS- during extinction in healthy individuals scoring relatively high on trait anxiety or relatively low on positive affect. These findings seem to suggest that safety learning is more vulnerable in healthy people with a high anxious disposition and/or relatively lower levels of positive affect. In addition, this is the first study to show that the negative impact of high trait anxiety on fear inhibition to safety cues during extinction can be countered by high levels of positive affect. These findings may have important clinical implications. ⋯ Both low positive affect and high trait anxiety are associated with impaired fear inhibition to nonpainful movements during fear extinction. Interestingly, high levels of positive affect buffer against the negative impact of trait anxiety. Increasing positive affect during exposure may counter the effects of trait vulnerabilities and improve treatment outcomes.
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The purpose of this study was to examine exercise-induced pain modulation in diabetic adults with painful diabetic neuropathy (PDN) compared to diabetic adults without PDN. Eighteen adults diagnosed with type 2 diabetes with and without PDN (mean age of 49 years) completed 2 sessions. During the familiarization session, participants completed questionnaires, were familiarized with the pain testing protocols, and completed maximal isometric contractions. During the exercise session, experimental pain testing was completed before and following exercise consisting of 3 minutes of isometric exercise performed at 25% maximal voluntary contraction. Ratings of perceived exertion and muscle pain were assessed every 30 seconds during exercise. Results indicated that ratings of perceived exertion and muscle pain during exercise were significantly higher (P < .05) for diabetic adults with PDN versus diabetic adults without PDN. Diabetic adults with PDN did not experience changes in thermal pain ratings following exercise, whereas diabetic adults without PDN reported significantly lower pain ratings following exercise. It is concluded that diabetic adults with PDN experienced high levels of muscle pain during exercise and a lack of exercise-induced hypoalgesia following exercise, in comparison to diabetic adults without PDN, who experienced lower levels of muscle pain during exercise and a hypoalgesic response following exercise. ⋯ Very little research has been conducted examining the impact of exercise on pain modulation in diabetic adults with PDN. This study provides support that adults with PDN exhibit exercise-induced endogenous pain modulatory system dysfunction.