Pain
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Fibromyalgia is a highly heterogeneous condition, but the most common symptoms are widespread pain, fatigue, poor sleep, and low mood. Nonpharmacological interventions are recommended as first-line treatment of fibromyalgia. However which interventions are effective for the different symptoms is not well understood. ⋯ Mind-body and strengthening exercises improved fatigue (ES -0.77 to -1.00), whereas aerobic and strengthening exercises improved sleep (ES -0.74 to -1.33). Psychological treatments including cognitive behavioural therapy and mindfulness improved FIQ, pain, sleep, and depression (ES -0.35 to -0.55) but not fatigue. The findings of this study suggest that nonpharmacological interventions for fibromyalgia should be individualised according to the predominant symptom.
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Activation of cannabinoid receptor type 1 (CB 1 ) produces analgesia in a variety of preclinical models of pain; however, engagement of central CB 1 receptors is accompanied by unwanted side effects, such as psychoactivity, tolerance, and dependence. Therefore, some efforts to develop novel analgesics have focused on targeting peripheral CB 1 receptors to circumvent central CB 1 -related side effects. In the present study, we evaluated the effects of acute and repeated dosing with the peripherally selective CB 1 -preferring agonist CB-13 on nociception and central CB 1 -related phenotypes in a model of inflammatory pain in mice. ⋯ This suggests that repeated CB-13 dosing leads to increased CNS exposure and unwanted engagement of central CB 1 receptors. Thus, caution is warranted regarding therapeutic use of CB-13 with the goal of avoiding CNS side effects. Nonetheless, the clear analgesic effect of acute peripheral CB 1 receptor activation suggests that peripherally restricted cannabinoids are a viable target for novel analgesic development.
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Prdm12 is a conserved epigenetic transcriptional regulator that displays restricted expression in nociceptors of the developing peripheral nervous system. In mice, Prdm12 is required for the development of the entire nociceptive lineage. In humans, PRDM12 mutations cause congenital insensitivity to pain, likely because of the loss of nociceptors. ⋯ Phenotypically, we observed that mice lacking Prdm12 exhibit normal responses to thermal and mechanical nociceptive stimuli but a reduced response to capsaicin and hypersensitivity to formalin-induced inflammatory pain. Together, our data indicate that Prdm12 regulates pain-related behavior in a complex way by modulating gene expression in adult nociceptors and controlling their excitability. The results encourage further studies to assess the potential of Prdm12 as a target for analgesic development.
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Observational Study
Long-term neuropathic pain behaviors correlate with synaptic plasticity and limbic circuits alteration: a comparative observational study in mice.
Neuropathic pain has long-term consequences in affective and cognitive disturbances, suggesting the involvement of supraspinal mechanisms. In this study, we used the spared nerve injury (SNI) model to characterize the development of sensory and aversive components of neuropathic pain and to determine their electrophysiological impact across prefrontal cortex and limbic regions. Moreover, we evaluated the regulation of several genes involved in immune response and inflammation triggered by SNI. ⋯ On the other hand, a reduced neural activity was recorded in the lateral entorhinal cortex-dentate gyrus pathway in the 1-month SNI mice, but not in the 12-month SNI mice. Finally, we observed the upregulation of specific genes involved in immune response in the hippocampus of 1-month SNI mice, but not in the 12-month SNI mice, suggesting a neuroinflammatory response that may contribute to the SNI phenotype. These data suggest that distinct brain circuits may drive the psychiatric components of neuropathic pain and pave the way for better investigation of the long-term consequences of peripheral nerve injury for which most of the available drugs are to date unsatisfactory.
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This study aimed to identify patterns of opioid dispensing in Australian workers with low back pain (LBP) and determine the association of dispensing patterns with wage replacement duration. Australian workers' compensation claimants with LBP and at least 1 day of wage replacement were included. We used group-based trajectory modelling to identify opioid dispensing patterns over a two-and-a-half-year period from reported LBP onset and quantile regression to compare wage replacement duration between each dispensing pattern group. ⋯ In addition, moderate-volume and high-volume long-term dispensing groups had significantly longer wage replacement duration compared with the short-term dispensing group (median [weeks]: 126.9, 126.0, and 30.7, respectively). Without controlling for pain severity, these results offer limited evidence that opioids lead to longer wage replacement duration. Further research controlling for pain severity, psychosocial factors, and recovery expectations is required to confirm whether the relationship between opioid dispensing pattern and wage replacement duration is causal in nature.