Context Veratramine may have a potential therapeutic effect for diabetic peripheral neuropathy (DPN). Objective To evaluate whether veratramine ameliorates neuropathic pain in a rat diabetic model. Materials and methods Sprague–Dawley rats were used for a diabetic model induced by a streptozotocin + high-fat diet. Two months after the induction of the diabetic model, the rats with DPN were screened according to the mechanical pain threshold. The rats with DPN were divided into a model group (n = 12) and a treated group (n = 12). Rats with diabetes, but without peripheral neuropathy, were used in the vehicle group (n = 9). The treatment group received 50 μg/kg veratramine via the tail vein once a day for 4 weeks. During modelling and treatment, rats in all three groups were fed a high-fat diet. Results The mechanical withdrawal threshold increased from 7.5 ± 1.9 N to 17.9 ± 2.6 N in DPN rats treated with veratramine. The tolerance time of the treated group to hot and cold ectopic pain increased from 11.8 ± 4.2 s and 3.4 ± 0.8 s to 20.4 ± 4.1 s and 5.9 ± 1.7 s, respectively. Veratramine effectively alleviated L4-L5 spinal cord and sciatic nerve pathological injury. Veratramine inhibited the expression of SIGMAR1 and the phosphorylation of the N-methyl-d-aspartate receptor (NMDAR) Ser896 site in spinal cord tissue, as well as inhibited the formation of SIGMAR1-NMDAR and NMDAR-CaMKII complexes. Discussion and conclusions Veratramine may alleviate the occurrence of pain symptoms in rats with DPN by inhibiting activation of the SIGMAR1-NMDAR pathway.

To assess and evaluate Chitosan-Metamizole nanoparticles for fracture healing and analgesic potential, nanoparticles were formulated using the ionotropic gelation method. The nanoparticles were evaluated for particle size, zeta potential, polydispersity index, loading efficiency, surface characteristics and drug release properties. The analgesic activity was determined in carrageenan-induced arthritic male Wister rats. Further fracture healing potency, mechanical testing, radiographic examination and bone histology of the femur were studied. The drug loading efficiency of 11.38%-17.45%, particle size of 140-220 nm, and zeta potential of 19.12-23.14 mV were observed with a spherical, smooth appearance. Nanoparticles showed sustained release behaviour over a longer period. Nearly 4-fold inhibition of oedema was observed in animals treated with nanoparticles with excellent fracture healing potential. The femurs treated with nanoparticles required greater force to fracture. Nanoparticles significantly improved the strength and healing process. Histopathological studies showed the potential of nanoparticles in the healing process. The study confirmed the potential of nanoparticles in fracture healing and enhancement of analgesic activity. K E Y W O R D Sanalgesic, bone, chitosan, fracture healing, metamizole, nanoparticles Li Yin and Liyong Yuan contributed equally to the article.