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Background and Purpose Neuropathic pain is a widespread health problem with limited curative treatment. Decreased sarco/endoplasmic reticulum Ca2+‐ATPase (SERCA) expression has been reported in dorsal root ganglion (DRG) of animals suffering from neuropathic pain. We aimed to establish the relationship between SERCA expression and the pain responses and to elucidate the underlying molecular mechanism. Experimental Approach Neuropathic pain was modelled using rat chronic constriction injury (CCI). Ca2+ imaging and current clamp patch‐clamp were used to determine cytosolic Ca2+ levels and action potential firing, respectively. Western blots, immunofluorescence staining and qRT‐PCR were used to quantitatively assess protein and mRNA expression, respectively. H&E staining and coupled enzyme assays were used to evaluate the nerve injury and SERCA2b activity, respectively. Key Results SERCA2b is the predominant SERCA isoform in rat DRG and its expression is decreased after CCI at mRNA, protein and activity levels. Whereas inhibiting SERCA with thapsigargin causes neuronal hyperexcitation, nerve injury, endoplasmic reticulum (ER) stress, satellite glial cell activation and mechanical allodynia, activating SERCA by CDN1163 or overexpressing SERCA2b in DRG after CCI produces long‐term relief of mechanical and thermal allodynia accompanied by morphological and functional restoration through alleviation of ER stress. Furthermore, the down‐regulation of DRG SERCA2b in CCI rats is caused by increased production of ROS through Sp1‐dependent transcriptional inhibition. Conclusion and Implications Our findings reveal a novel pathway centring around SERCA2b as the key molecule underlying the mechanism of development and maintenance of neuropathic pain, and SERCA2b activators have the potential for therapeutic treatment of neuropathic pain.

Nine new cadinane sesquiterpenoids, alanenses A−I (1−9), were isolated from the leaves of Alangium chinense together with three previously reported analogues (10−12). The structures of these molecules were elucidated by interpretation of spectroscopic and spectrometric data. Absolute configurations were established by the comparison of experimental and calculated ECD data, chemical degradation studies for sugar moieties, and a single-crystal X-ray diffraction analysis. Compounds 1 and 2 were isolated as racemates, and enantiopurification was achieved by chiral HPLC. Compounds 3−5 are glycosylated cadinanes bearing a β-D-glucose unit, while compounds 6−9 incorporate a hydroxymethyl group in either the free form or additional ring fusion. The structure of compound 11 was originally misassigned and later revised using additional NMR data. The corrected structure is here supported by X-ray single-crystal analysis. Compounds 1 and 2 inhibit spontaneous calcium channel oscillations at low micromolar concentrations.

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Thirteen new benzamide alkaloids, delphiniumines A−M (1−13), together with one known analogue ( 14), were isolated from Delphinium anthriscifolium Hance. All of the structures were determined by spectroscopic and spectrometric analyses. Absolute configuration for 1 was established using experimental and calculated ECD data, as well as by X-ray crystallography analysis. Compound 1 possesses a previously undescribed polysubstituted cyclopentene carbon framework. Compound 2 was isolated as an artifact from 1 during the extraction process. Compound 7 is glycosylated with a β-D-glucose unit. Compound 13 bears a chlorine substituent. At a concentration of 10 μM, compounds 6, 8, and 10−12 suppressed LPS-induced NO production in RAW264.7 cells with inhibition rates ranging from 40.3% to 78.8%.