Pain
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Review
Towards a new model of attentional biases in the development, maintenance, and management of pain.
Individuals with chronic pain demonstrate attentional biases (ABs) towards pain-related stimuli. However, the clinical importance of these biases is yet to be determined and a sound theoretical model for explaining the role of ABs in the development and maintenance of pain is lacking. ⋯ Interventions targeting ABs were less consistent; however, there were promising findings among studies that found attentional training effects, particularly for laboratory research. The proposed Threat Interpretation Model suggests a relationship between threat, interpretation, and stimuli in determining attentional processes, which while tentative generates important testable predictions regarding the role of attention in pain and builds on previous theoretical and empirical work in this area.
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Tumor cells frequently metastasize to bone where they can generate cancer-induced bone pain (CIBP) that can be difficult to fully control using available therapies. Here, we explored whether PLX3397, a high-affinity small molecular antagonist that binds to and inhibits phosphorylation of colony-stimulating factor-1 receptor, the tyrosine-protein kinase c-Kit, and the FMS-like tyrosine kinase 3, can reduce CIBP. These 3 targets all regulate the proliferation and function of a subset of the myeloid cells including macrophages, osteoclasts, and mast cells. ⋯ Administration of PLX3397 was initiated on day 14 after prostate cancer cell injection when the tumor was well established, and tumor-induced bone remodeling was first evident. Over the next 6 weeks, sustained administration of PLX3397 attenuated CIBP behaviors by approximately 50% and was equally efficacious in reducing tumor cell growth, formation of new tumor colonies in bone, and pathological tumor-induced bone remodeling. Developing a better understanding of potential effects that analgesic therapies have on the tumor itself may allow the development of therapies that not only better control the pain but also positively impact disease progression and overall survival in patients with bone cancer.
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Activity treatments, such as treadmill exercise, are used to improve functional recovery after nerve injury, parallel to an increase in neurotrophin levels. However, despite their role in neuronal survival and regeneration, neurotrophins may cause neuronal hyperexcitability that triggers neuropathic pain. ⋯ Injury also induced Na⁺-K⁺-2Cl⁻ cotransporter 1 (NKCC1) upregulation in DRG, and K⁺-Cl⁻ cotransporter 2 (KCC2) downregulation in lumbar spinal cord dorsal horn. iTR normalized NKCC1 and boosted KCC2 expression, together with a significant reduction of microgliosis in L3-L5 dorsal horn, and a reduction of BDNF expression in microglia at 1 to 2 weeks postinjury. These data demonstrate that specific activity protocols, such as iTR, can modulate neurotrophins expression after peripheral nerve injury and prevent neuropathic pain by blocking early mechanisms of sensitization such as collateral sprouting and NKCC1/KCC2 disregulation.
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Glycine transporter 1 (GlyT1) plays a crucial role in regulating extracellular glycine concentrations and might thereby constitute a new drug target for the modulation of glycinergic inhibition in pain signaling. Consistent with this view, inhibition of GlyT1 has been found to induce antinociceptive effects in various animal pain models. We have shown previously that the lidocaine metabolite N-ethylglycine (EG) reduces GlyT1-dependent glycine uptake by functioning as an artificial substrate for this transporter. ⋯ Additionally, we found that EG reduced the increase in neuronal firing of wide-dynamic-range neurons caused by inflammatory pain induction. These findings suggest that systemically applied lidocaine exerts antihyperalgesic effects through its metabolite EG in vivo, by enhancing spinal inhibition of pain processing through GlyT1 modulation and subsequent increase of glycine concentrations at glycinergic inhibitory synapses. EG and other substrates of GlyT1, therefore, may be a useful therapeutic agent in chronic pain states involving spinal disinhibition.
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Randomized Controlled Trial
Ultrasound guided intra-articular and rotator interval corticosteroid injections in adhesive capsulitis of the shoulder. A double blind, sham controlled randomized study.
Adhesive capsulitis (frozen shoulder) is a common cause of shoulder pain and disability. Previous studies have reported that intra-articular corticosteroid injections are of benefit compared with placebo up to 6 weeks. It has been suggested that the structures primarily involved in adhesive capsulitis are the capsule and the rotator interval. ⋯ The significant group differences were maintained at week 12 but not at week 26. Similar results were found for the secondary outcome measures (night pain, Shoulder Pain and Disability Index). Differences between the corticosteroid groups were not significant at any time.