RESUMEN
Diabetic peripheral neuropathy (DPN) is a prevalent complication of diabetes mellitus that is caused by metabolic toxicity to peripheral axons. We aimed to gain deep mechanistic insight into the disease process using bulk and spatial RNA sequencing on tibial and sural nerves recovered from lower leg amputations in a mostly diabetic population. First, our approach comparing mixed sensory and motor tibial and purely sensory sural nerves shows key pathway differences in affected nerves, with distinct immunological features observed in sural nerves. Second, spatial transcriptomics analysis of sural nerves reveals substantial shifts in endothelial and immune cell types associated with severe axonal loss. We also find clear evidence of neuronal gene transcript changes, like PRPH, in nerves with axonal loss suggesting perturbed RNA transport into distal sensory axons. This motivated further investigation into neuronal mRNA localization in peripheral nerve axons generating clear evidence of robust localization of mRNAs such as SCN9A and TRPV1 in human sensory axons. Our work gives new insight into the altered cellular and transcriptomic profiles in human nerves in DPN and highlights the importance of sensory axon mRNA transport as an unappreciated potential contributor to peripheral nerve degeneration.
RESUMEN
BACKGROUND: Interscalene nerve block (INB) has become a popular technique for shoulder anesthesia. However, INB is associated with complication rates as high as 20%. Local liposomal bupivacaine (LLB) is an alternative to INB that potentially offers extended pain control with fewer adverse effects. METHODS: We conducted a dual-center randomized controlled trial of 108 participants who were treated with LLB (n = 54) or INB (n = 54) to control pain after shoulder arthroplasty. We assessed visual analog scale pain scores at 6-hour intervals from 6 to 96 hours postoperatively and at the first postoperative visit. We assessed opioid medication consumption intraoperatively and on days 1, 2, 3, and 4 postoperatively, as well as the duration of hospital and postanesthesia care unit (PACU) stays. RESULTS: At 6 hours postoperatively, the mean visual analog scale pain score was lower in the INB group (2.9 ± 3.1) than in the LLB group (5.1 ± 2.9, P < .01). The INB group consumed less opioid medication during the first 24 hours postoperatively (18 ± 12 morphine milligram equivalents) than did the LLB group (36 ± 48 morphine milligram equivalents, P = .01). The PACU stay was shorter in the INB group (102 ± 53 minutes) compared with the LLB group (139 ± 77 minutes, P < .01). CONCLUSIONS: Compared with LLB, INB provides better pain control immediately after shoulder arthroplasty as evidenced by shorter PACU stays, lower pain scores at 6 hours postoperatively, and less opioid medication consumption during the first 24 hours postoperatively. However, no differences in outcomes were observed between groups beyond 24 hours.