Pain
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Persistent itch is a common symptom of allergic contact dermatitis (ACD) and represents a significant health burden. The chemokine CXCL10 is predominantly produced by epithelial cells during ACD. Although the chemokine CXCL10 and its receptor CXCR3 are implicated in the pathophysiology of ACD, it is largely unexplored for itch and pain accompanying this disorder. ⋯ These results suggest that CXCL10/CXCR3 signaling mediates allergic itch but not inflammatory pain in the context of skin inflammation. Thus, upregulation of CXCL10/CXCR3 signaling in sensory neurons may contribute to itch associated with ACD. Targeting the CXCL10/CXCR3 signaling might be beneficial for the treatment of allergic itch.
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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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A large number of analgesics have failed to prove superiority over placebo in randomized controlled trials (RCTs), and as this has been related to increasing placebo responses, there is currently an interest in specifying predictors of the placebo response. The literature on placebo mechanisms suggests that factors related to patients' expectations of treatment efficacy are pivotal for the placebo response. Also, general characteristics of RCTs have been suggested to influence the placebo response. ⋯ Opioid trials, a high number of planned face-to-face visits, and randomization ratio predicted the magnitude of the placebo response, thereby supporting the expectancy hypothesis. Exploratory models with baseline pain intensity, age, washout length, and discontinuation because of adverse events accounted for approximately 10% of the variability in the placebo response. Based on these results and previous mechanisms studies, we think that patients' perception of treatment allocation and expectations toward treatment efficacy could potently predict outcomes of RCTs.
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Randomized Controlled Trial Multicenter Study
Efficacy and Safety of Tanezumab in the Treatment of Pain from Bone Metastases.
Patients with metastatic bone cancer report life-altering pain. Nerve growth factor is involved in pain signaling. Tanezumab, a nerve growth factor monoclonal antibody, has demonstrated efficacy in chronic pain. ⋯ Adverse event incidence of study 1003 was similar between groups. Although the primary endpoint was not achieved, tanezumab may provide additional sustained analgesia in patients with metastatic bone pain taking daily opioids. Additional larger studies are warranted.