Background: Facial pain in multiple sclerosis is often due to trigeminal neuralgia but atypical pictures can be observed. Case presentation: A man with primary progressive multiple sclerosis developed severe unilateral facial pain in the right orbital region. Spontaneous and triggered attacks were associated with ipsilateral conjunctival injection and lacrimation. A diagnosis of short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing was made, and symptoms significantly improved with lamotrigine. Conclusion: Pain is poorly investigated in multiple sclerosis, with a dramatic impact on patients’ life quality. In this light, standardized evaluation of pain is needed to improve patient management.

2024-06-01·The American Journal of Surgery

Pain and opioid use after colorectal resection for benign versus malignant disease: A single institution analysis

Article

作者: Brockhaus, Kara K ; Colom, Sara M ; Bobel, Matthew C ; Diaz, Sarah ; Ramm, Carole ; Cleary, Robert K

BACKGROUNDStudies comparing opioid needs between benign and malignant colorectal diseases are inconclusive.METHODSSingle institution analysis of prospectively maintained colorectal surgery database. Multiple regression analyses done on perioperative numeric pain scores (NPS) and opioids prescribed at discharge.RESULTS641 patients in Benign and 276 patients in the Malignant group. Unadjusted comparison revealed significantly higher NPS for the Benign than the Malignant group preoperative and postoperative day 0 (after surgery), 1, 2, and 3 (all p ≤ 0.001). Opioids prescribed at discharge were significantly higher in the Benign group (60.0% vs 51.1%, p = 0.018). After regression analysis, there was no longer a significant difference in NPS (B = 0.703, p = 0.095) and opioids prescribed between groups [OR = 0.803 (95%CI 0.586, 1.1), p = 0.173].CONCLUSIONSPain and opioids prescribed at discharge are not significantly different between benign and malignant diseases in an enhanced recovery pain management pathway that maximizes non-opioid multimodal analgesic strategies.

2024-05-21·Angewandte Chemie International Edition

Asymmetric Carbene‐Alkyne Metathesis‐Mediated Cascade: Synthesis of Benzoxazine Polychiral Polyheterocycles and Discovery of a Novel Pain Blocker

Article

作者: Li, Fuyi ; Cai, Shuxian ; Li, Yukai ; Liu, Wenjiang ; Cai, Song ; Hu, Wenhao ; Shi, Taoda ; Liu, Shuhao ; Yang, Haoyi ; Jia, Shikun ; Wu, Linna ; Zhang, Zhijing ; Guo, Weijie ; Shu, Jirong

AbstractThis study introduces a novel approach for synthesizing Benzoxazine‐centered Polychiral Polyheterocycles (BPCPHCs) via an innovative asymmetric carbene‐alkyne metathesis‐triggered cascade. Overcoming challenges associated with intricate stereochemistry and multiple chiral centers, the catalytic asymmetric Carbene Alkyne Metathesis‐mediated Cascade (CAMC) is employed using dirhodium catalyst/Brønsted acid co‐catalysis, ensuring precise stereo control as validated by X‐ray crystallography. Systematic substrate scope evaluation establishes exceptional diastereo‐ and enantioselectivities, creating a unique library of BPCPHCs. Pharmacological exploration identifies twelve BPCPHCs as potent Nav ion channel blockers, notably compound 8 g. In vivo studies demonstrate that intrathecal injection of 8 g effectively reverses mechanical hyperalgesia associated with chemotherapy‐induced peripheral neuropathy (CIPN), suggesting a promising therapeutic avenue. Electrophysiological investigations unveil the inhibitory effects of 8 g on Nav1.7 currents. Molecular docking, dynamics simulations and surface plasmon resonance (SPR) assay provide insights into the stable complex formation and favorable binding free energy of 8 g with C5aR1. This research represents a significant advancement in asymmetric CAMC for BPCPHCs and unveils BPCPHC 8 g as a promising, uniquely acting pain blocker, establishing a C5aR1‐Nav1.7 connection in the context of CIPN.

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