ESRRG-controlled downregulation of KCNN1 in primary sensory neurons is required for neuropathic pain.

Peripheral nerve injury-induced neuronal hyperactivity in the dorsal root ganglion (DRG) participates in neuropathic pain. The calcium-activated potassium channel subfamily N member 1 (KCNN1) mediates action potential afterhyperpolarization (AHP) and gates neuronal excitability. However, the specific contribution of DRG KCNN1 to neuropathic pain is not yet clear. We report that chronic constriction injury (CCI) of the unilateral sciatic nerve or unilateral ligation of the fourth lumbar nerve produced the downregulation of Kcnn1 mRNA and KCNN1 protein in the injured DRG. This downregulation was partially attributed to a decrease in DRG estrogen-related receptor gamma (ESRRG), a transcription factor, which led to reduced binding to the Kcnn1 promoter. Rescuing this downregulation prevented CCI-induced decreases in total potassium voltage currents and AHP currents, reduced excitability in the injured DRG neurons, and alleviated CCI-induced development and maintenance of nociceptive hypersensitivities, without affecting locomotor function and acute pain. Mimicking the CCI-induced DRG KCNN1 downregulation resulted in augmented responses to mechanical, heat, and cold stimuli in naive mice. Our findings indicate that ESRRG-controlled downregulation of DRG KCNN1 is likely essential for the development and maintenance of neuropathic pain. Thus, KCNN1 may serve as a potential target for managing this disorder.

Elastin expression in the conjoint fascial sheath and levator palpebrae superioris muscle of children with unilateral severe congenital ptosis with different muscle strengths.

Elastin expression in the conjoint facial sheath (CFS) of patients of different ages with severe ptosis has been extensively studied, but its expression in the CFS of pediatric patients with severe ptosis with different muscle strengths remains poorly understood. The aim of the present study was to investigate the expression of elastin in the CFS and levator palpebrae superioris muscle (LM) of children with severe congenital ptosis with different LM strengths. In total, 20 pediatric patients with unilateral severe congenital ptosis (20 eyes) were included, who underwent CFS + LM complex suspension surgery from June 2020 to February 2022. Among these patients, the LM strength was 0-1 mm in 10 patients and 2-3 mm in the other 10 patients. Excess CFS and LM tissue samples were obtained from the patients during surgery, before the protein expression levels of elastin in the specimens were measured by western blotting. During the 6-month postoperative follow-up period, the good correction rate, the degree of incomplete eyelid closure and the incidence of complications were observed. Western blotting results showed that, compared with that in the 0-1 mm group, elastin expression was not significantly different in the CFS, whereas it was significantly increased (P=0.021) in the LM of the 2-3 mm group. In addition, elastin expression in the CFS was markedly higher compared with that in the LM in both groups (in the 0-1 mm group, P=0.005; in the 2-3 mm group, P=0.009). Additionally, the curative effect evaluation revealed that the good correction rates in the 0-1 and 2-3 mm groups were 90 and 100%, respectively. In total, 3 patients experienced conjunctival prolapse during the follow-up period, including 2 patients in the 0-1 mm group and 1 patient in the 2-3 mm group, but there were no other complications. To conclude, elastin expression in the CFS was found to be higher compared with that in the LM of children with severe congenital ptosis. Although elastin expression in the LM was positively associated with LM strength, its expression in the CFS displayed no clear association with LM function. Therefore, these observations suggested that CFS + LM complex suspension surgery is viable to correct severe congenital ptosis in pediatric patients.