Acute inflammatory response via neutrophil activation protects against the development of chronic pain.

The transition from acute to chronic pain is critically important but not well understood. Here, we investigated the pathophysiological mechanisms underlying the transition from acute to chronic low back pain (LBP) and performed transcriptome-wide analysis in peripheral immune cells of 98 participants with acute LBP, followed for 3 months. Transcriptomic changes were compared between patients whose LBP was resolved at 3 months with those whose LBP persisted. We found thousands of dynamic transcriptional changes over 3 months in LBP participants with resolved pain but none in those with persistent pain. Transient neutrophil-driven up-regulation of inflammatory responses was protective against the transition to chronic pain. In mouse pain assays, early treatment with a steroid or nonsteroidal anti-inflammatory drug (NSAID) also led to prolonged pain despite being analgesic in the short term; such a prolongation was not observed with other analgesics. Depletion of neutrophils delayed resolution of pain in mice, whereas peripheral injection of neutrophils themselves, or S100A8/A9 proteins normally released by neutrophils, prevented the development of long-lasting pain induced by an anti-inflammatory drug. Analysis of pain trajectories of human subjects reporting acute back pain in the UK Biobank identified elevated risk of pain persistence for subjects taking NSAIDs. Thus, despite analgesic efficacy at early time points, the management of acute inflammation may be counterproductive for long-term outcomes of LBP sufferers.

Predicting lymph node metastases with endoscopic resection in cT2N0M0 oesophageal cancer: A systematic review and meta-analysis.

BACKGROUND: Despite modern imaging modalities, staging of clinically staged T2N0M0 (cT2N0M0) oesophageal cancer is suboptimal, often leading to overtreatment. Endoscopic resection - the first-line therapy for early localised tumours - could be used to improve staging and to attain predictors of nodal upstaging enabling more stage-guided treatment decisions. OBJECTIVE: A systematic literature review and a meta-analysis were conducted to assess the prevalence and the pathological risk factors of lymph node metastases in cT2N0M0 oesophageal cancer. METHODS: Databases of PUBMED, EMBASE and Cochrane were searched for literature. The primary outcome was lymph node metastases determined after primary surgical resection. RESULTS: Nine studies with a total of 1650 cT2N0M0 patients were included. The prevalence of lymph node metastases was 43% (95% confidence interval: 35-50%) with heterogeneity being high across studies (I2 = 0.86, p < 0.001). Factors potentially attainable by endoscopic resection and having a significant association with lymph node metastases were invasion depth, differentiation grade, tumour size, depth of invasion in the muscularis propria and lymphovascular invasion. CONCLUSIONS: Clinical lymph node staging is inaccurate in almost half of cT2N0M0 oesophageal cancer. Endoscopic resection is a promising diagnostic modality that might even be a valid alternative to surgery in selected patients without high-risk features, but further evidence is warranted.