Sex Differences in Oxycodone/Naloxone vs. Tapentadol in Chronic Non-Cancer Pain: An Observational Real-World Study

Barrachina, Jordi; Margarit, César; Muriel, Javier; López-Gil, Vicente; López-Gil, Santiago; Ballester, Pura; Mira-Lorente, Laura; Agulló, Laura; Peiró, Ana M.

doi:10.3390/biomedicines10102468

Cited by 6 publications

(4 citation statements)

References 56 publications

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“…Interestingly, this can have a sex impact due to the higher tramadol female prescriptions in front of men recorded in national databases from Denmark, Norway, and Sweden [ 32 ]. This tendency has been confirmed in the Spanish population, where females have a higher number of tramadol prescriptions compared to a higher dose for males [ 33 ]. These differences should be considered with drug abuse cases or even as a predictor of failed analgesic therapies, which should include a sex-differences analysis.…”

Section: Discussionmentioning

confidence: 79%

Pharmacogenetic Guided Opioid Therapy Improves Chronic Pain Outcomes and Comorbid Mental Health: A Randomized, Double-Blind, Controlled Study

Agulló

Aguado²,

Muriel

et al. 2023

IJMS

Self Cite

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Interindividual variability in analgesic response is at least partly due to well-characterized polymorphisms that are associated with opioid dosing and adverse outcomes. The Clinical Pharmacogenetics Implementation Consortium (CPIC) has put forward recommendations for the CYP2D6 phenotype, but the list of studied drug-gene pairs continues to grow. This clinical trial randomized chronic pain patients (n = 60), referred from primary care to pain unit care into two opioid prescribing arms, one guided by CYP2D6, μ-opioid receptor (OPRM1), and catechol-O-methyl transferase (COMT) genotypes vs. one with clinical routine. The genotype-guided treatment reduced pain intensity (76 vs. 59 mm, p < 0.01) by improving pain relief (28 vs. 48 mm, p < 0.05), increased quality of life (43 vs. 56 mm p < 0.001), and lowered the incidence of clinically relevant adverse events (3 [1–5] vs. 1 [0–2], p < 0.01) and 42% opioid dose (35 [22–61] vs. 60 [40–80] mg/day, p < 0.05) as opposed to usual prescribing arm. The final health utility score was significantly higher (0.71 [0.58–0.82] vs. 0.51 [0.13–0.67] controls, p < 0.05) by improving sleepiness and depression comorbidity, with a significant reduction of 30–34% for headache, dry mouth, nervousness, and constipation. A large-scale implementation analysis could help clinical translation, together with a pharmaco-economic evaluation.

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Section: Discussionmentioning

confidence: 79%

Pharmacogenetic Guided Opioid Therapy Improves Chronic Pain Outcomes and Comorbid Mental Health: A Randomized, Double-Blind, Controlled Study

Agulló

Aguado²,

Muriel

et al. 2023

IJMS

Self Cite

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show abstract

“…Additionally, a study included in our semi-systematic review found that women report more the use NSAIDs than men 46 . In another study of patients receiving oxycodone, females received higher morphine equivalent daily dose of opioid than men 67 . However, a study on postoperative opioid prescriptions after surgery showed that patient and provider demographic characteristics influenced doses prescribed, with males prescribed higher morphine milligram equivalents 68 .…”

Section: Discussionmentioning

confidence: 98%

Sex-differences in prostaglandin signaling: a semi-systematic review and characterization of PTGDS expression in human sensory neurons

Shen

Sankaranarayanan

Price

et al. 2023

Sci Rep

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There is increasing evidence of sex differences in underlying mechanisms causing pain in preclinical models, and in clinical populations. There are also important disconnects between clinical pain populations and the way preclinical pain studies are conducted. For instance, osteoarthritis pain more frequently affects women, but most preclinical studies have been conducted using males in animal models. The most widely used painkillers, nonsteroidal anti-inflammatory drugs (NSAIDs), act on the prostaglandin pathway by inhibiting cyclooxygenase (COX) enzymes. The purpose of this study was to analyze the preclinical and clinical literature on the role of prostaglandins and COX in inflammation and pain. We aimed to specifically identify studies that used both sexes and investigate whether any sex-differences in the action of prostaglandins and COX inhibition had been reported, either in clinical or preclinical studies. We conducted a PubMed search and identified 369 preclinical studies and 100 clinical studies that matched our inclusion/exclusion criteria. Our analysis shows that only 17% of preclinical studies on prostaglandins used both sexes and, out of those, only 19% analyzed or reported data separated by sex. In contrast, 79% of the clinical studies analyzed used both sexes. However, only 6% of those reported data separated by sex. Interestingly, 14 out of 15 preclinical studies and 5 out of 6 clinical studies that analyzed data separated by sex have identified sex-differences. This builds on the increasing evidence of sex-differences in prostaglandin signaling and the importance of sex as a biological variable in data analysis. The preclinical literature identifies a sex difference in prostaglandin D2 synthase (PTGDS) expression where it is higher in female than in male rodents in the nervous system. We experimentally validated that PTGDS expression is higher in female human dorsal root ganglia (DRG) neurons recovered from organ donors. Our semi-systematic literature review reveals a need for continued inclusivity of both male and female animals in prostaglandins studies and data analysis separated by sex in preclinical and clinical studies. Our finding of sex-differences in neuronal PTGDS expression in humans exemplifies the need for a more comprehensive understanding of how the prostaglandin system functions in the DRG in rodents and humans.

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“…In a study of NSAID prescriptions in the Danish population, women received more prescriptions for every NSAID than men [18]. In another study of patients receiving oxycodone, females received higher morphine equivalent daily dose of opioid than men [6]. However, a study on postoperative opioid prescriptions after surgery showed that patient and provider demographic characteristics influenced doses prescribed, with males prescribed higher morphine milligram equivalents [68].…”

Section: Discussionmentioning

confidence: 99%

Sex-differences in prostaglandin signaling: a semi-systematic review and characterization of PTGDS expression in human sensory neurons

Shen

Sankaranarayanan

Price

et al. 2022

Preprint

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There is increasing evidence of sex differences in underlying mechanisms causing pain in preclinical models, and in clinical populations. There are also important disconnects between clinical pain populations and the way preclinical pain studies are conducted. For instance, osteoarthritis pain more frequently affects women but most preclinical studies have been conducted using males in animal models. The most widely used painkillers, nonsteroidal anti-inflammatory drugs (NSAIDs), act on the prostaglandin pathway by inhibiting cyclooxygenase (COX) enzymes. The purpose of this study was to analyze the preclinical and clinical literature on the role of prostaglandins and COX in inflammation and pain. We aimed to specifically identify studies that used both sexes and investigate whether any sex-differences in the action of prostaglandins and COX inhibition had been reported, either in clinical or preclinical studies. We conducted a PubMed search and identified 369 preclinical studies and 100 clinical studies that matched our inclusion/exclusion criteria. Our analysis shows that only 17% of preclinical studies on prostaglandins used both sexes and, out of those, only 19% analyzed or reported data in a sex-aware fashion. In contrast, 79% of the clinical studies analyzed used both sexes. However, only 6% of those reported data in a sex-aware fashion. Interestingly, 14 out of 15 preclinical studies and 4 out of 5 clinical studies that analyzed data in a sex-aware fashion have identified sex-differences. This builds on the increasing evidence of sex-differences in prostaglandin signaling and the importance of sex-awareness in data analysis. The preclinical literature identifies a sex difference in prostaglandin D2 synthase (PTGDS) expression where it is higher in female than in male rodents in the nervous system. We experimentally validated that PTGDS expression is higher in female human dorsal root ganglia (DRG) neurons recovered from organ donors. Our semi-systematic literature review reveals a need for continued inclusivity of both male and female animals in prostaglandins studies and sex-aware analysis in data analysis in preclinical and clinical studies. Our finding of sex-differences in neuronal PTGDS expression in humans exemplifies the need for a more comprehensive understanding of how the prostaglandin system functions in the DRG in rodents and humans.

show abstract

Sex Differences in Oxycodone/Naloxone vs. Tapentadol in Chronic Non-Cancer Pain: An Observational Real-World Study

Cited by 6 publications

References 56 publications

Pharmacogenetic Guided Opioid Therapy Improves Chronic Pain Outcomes and Comorbid Mental Health: A Randomized, Double-Blind, Controlled Study

Pharmacogenetic Guided Opioid Therapy Improves Chronic Pain Outcomes and Comorbid Mental Health: A Randomized, Double-Blind, Controlled Study

Sex-differences in prostaglandin signaling: a semi-systematic review and characterization of PTGDS expression in human sensory neurons

Sex-differences in prostaglandin signaling: a semi-systematic review and characterization of PTGDS expression in human sensory neurons

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