ABSTRACT
STUDY DESIGN: Retrospective case control. OBJECTIVES: The purpose of the current study is to determine risk factors associated with chronic opioid use after spine surgery. METHODS: In our single institution retrospective study, 1,299 patients undergoing elective spine surgery at a tertiary academic medical center between January 2010 and August 2017 were enrolled into a prospectively collected registry. Patients were dichotomized based on renewal of, or active opioid prescription at 3-mo and 12-mo postoperatively. The primary outcome measures were risk factors for opioid renewal 3-months and 12-months postoperatively. These primarily included demographic characteristics, operative variables, and in-hospital opioid consumption via morphine milligram equivalence (MME). At the 3-month and 12-month periods, we analyzed the aforementioned covariates with multivariate followed by bivariate regression analyses. RESULTS: Multivariate and bivariate analyses revealed that script renewal at 3 months was associated with black race (P = 0.001), preoperative narcotic (P < 0.001) or anxiety/depression medication use (P = 0.002), and intraoperative long lumbar (P < 0.001) or thoracic spine surgery (P < 0.001). Lower patient income was also a risk factor for script renewal (P = 0.01). Script renewal at 12 months was associated with younger age (P = 0.006), preoperative narcotics use (P = 0.001), and ≥4 levels of lumbar fusion (P < 0.001). Renewals at 3-mo and 12-mo had no association with MME given during the hospital stay or with the usage of PCA (P > 0.05). CONCLUSION: The current study describes multiple patient-level factors associated with chronic opioid use. Notably, no metric of perioperative opioid utilization was directly associated with chronic opioid use after multivariate analysis.
ABSTRACT
BACKGROUND: There are clinically relevant sex differences in acute and chronic pain mechanisms, but we are only beginning to understand their mechanistic basis. Transcriptome analyses of rodent whole dorsal root ganglion (DRG) have revealed sex differences, mostly in immune cells. We examined the transcriptome and translatome of the mouse DRG with the goal of identifying sex differences. METHODS: We used translating ribosome affinity purification sequencing and behavioral pharmacology to test the hypothesis that in Nav1.8-positive neurons, most of which are nociceptors, translatomes would differ by sex. RESULTS: We found 80 genes with sex differential expression in the whole DRG transcriptome and 66 genes whose messenger RNAs were sex differentially actively translated (translatome). We also identified different motifs in the 3' untranslated region of messenger RNAs that were sex differentially translated. In further validation studies, we focused on Ptgds, which was increased in the translatome of female mice. The messenger RNA encodes the prostaglandin PGD2 synthesizing enzyme. We observed increased PTGDS protein and PGD2 in female mouse DRG. The PTGDS inhibitor AT-56 caused intense pain behaviors in male mice but was only effective at high doses in female mice. Conversely, female mice responded more robustly to another major prostaglandin, PGE2, than did male mice. PTGDS protein expression was also higher in female cortical neurons, suggesting that DRG findings may be generalizable to other nervous system structures. CONCLUSIONS: Our results demonstrate sex differences in nociceptor-enriched translatomes and reveal unexpected sex differences in one of the oldest known nociceptive signaling molecule families, the prostaglandins.
