Advancing the integration of biosignal-based automated pain assessment methods into a comprehensive model for addressing cancer pain.

BACKGROUND: Tailoring effective strategies for cancer pain management requires a careful analysis of multiple factors that influence pain phenomena and, ultimately, guide the therapy. While there is a wealth of research on automatic pain assessment (APA), its integration with clinical data remains inadequately explored. This study aimed to address the potential correlations between subjective and APA-derived objectives variables in a cohort of cancer patients. METHODS: A multidimensional statistical approach was employed. Demographic, clinical, and pain-related variables were examined. Objective measures included electrodermal activity (EDA) and electrocardiogram (ECG) signals. Sensitivity analysis, multiple factorial analysis (MFA), hierarchical clustering on principal components (HCPC), and multivariable regression were used for data analysis. RESULTS: The study analyzed data from 64 cancer patients. MFA revealed correlations between pain intensity, type, Eastern Cooperative Oncology Group Performance status (ECOG), opioids, and metastases. Clustering identified three distinct patient groups based on pain characteristics, treatments, and ECOG. Multivariable regression analysis showed associations between pain intensity, ECOG, type of breakthrough cancer pain, and opioid dosages. The analyses failed to find a correlation between subjective and objective pain variables. CONCLUSIONS: The reported pain perception is unrelated to the objective variables of APA. An in-depth investigation of APA is required to understand the variables to be studied, the operational modalities, and above all, strategies for appropriate integration with data obtained from self-reporting. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, number (NCT04726228), registered 27 January 2021, https://classic. CLINICALTRIALS: gov/ct2/show/NCT04726228?term=nct04726228&draw=2&rank=1.

Efficacy and safety of hydromorphone for cancer pain: a systematic review and meta-analysis.

BACKGROUND: Cancer pain significantly impacts individuals' quality of life, with opioids being employed as the primary means for pain relief. Nevertheless, concerns persist regarding the adverse reactions and effectiveness of opioids such as morphine. Hydromorphone, recognized as a potent opioid, is a viable alternative for managing cancer-related pain. The goal of this systematic review and meta-analysis was to determine the effectiveness and safety characteristics of hydromorphone in comparison to other opioids, as well as different methods of administering this medication within the scope of cancer pain treatment. METHODS: The PubMed, Embase, Cochrane Library, Scopus, and Web of Science databases were searched on December 25th, 2023. Following the PRISMA guidelines, a systematic investigation of databases was carried out, and suitable studies were chosen according to predetermined criteria (PICO framework). The meta-analyses were performed using a random-effects model. RESULTS: This review included 18 RCTs with 2271 patients who compared hydromorphone with morphine, oxycodone, or fentanyl, as well as other types of hydromorphone. Hydromorphone demonstrated efficacy similar to that of morphine and oxycodone in reducing cancer pain intensity, decreasing additional analgesic consumption, and improving quality of life. However, morphine showed slight superiority over hydromorphone in reducing breakthrough pain. Adverse events were comparable between hydromorphone and morphine or oxycodone. Patient-controlled and clinician-controlled hydromorphone administration routes yielded similar outcomes. CONCLUSIONS: The outcomes of this study substantiate the efficacy of hydromorphone in the management of cancer-related pain, demonstrating similar levels of effectiveness and safety as morphine and oxycodone. These findings are consistent with prior comprehensive analyses, suggesting that hydromorphone is a feasible choice for alleviating cancer-associated pain. Additional investigations are warranted to determine its efficacy in distinct patient cohorts and for different modes of administration. TRIAL REGISTRATION: Prospero registration ID: CRD42024517513. Link: https://www.crd.york.ac.uk/PROSPERO/#recordDetails .

Comparison ultrasound-guided adductor canal block and surgeon-performed block for pain management after total knee arthroplasty: a prospective randomized controlled study.

OBJECTIVE: Adductor canal block (ACB) is widely performed for postoperative analgesia for total knee arthroplasty (TKA). The aim of this study is to compare surgeon-assisted and anesthesiologist-assisted (ultrasound-guided) adductor blocks in terms of postoperative analgesic efficacy. METHODS: This study was designed as a double-blind, prospective and randomized trial. A total of 240 participants were randomly allocated to three groups: one where the surgeon performed the adductor canal block (ACBs), another where it was conducted by an anesthetist with ultrasound guidance (ACBa), and a third group without the adductor block. The follow-up management after the Total Knee Arthroplasty (TKA) procedure occurred on the first, third, and tenth days, as well as the twelfth week. Outcome measures comprised pain assessment using the Visual Analog Scale (VAS) and monitoring opioid analgesic consumption. RESULTS: No significant differences in demographic profiles were observed between the groups. Groups ACBa and ACBs exhibited significantly lower VAS scores compared to the control group at both 3 and 12 h after surgery, with group ACBa showing the lowest VAS scores among all groups. However, at 1 day, 3 days, 10 days and 12 weeks after surgery, there was no significant difference in VAS scores between the ACBa and ACBs groups. On the first three days, the ACBa group had the lowest opioid consumption and the lowest total opioid consumption. The differences in VAS scores between the groups began to decrease on the first day after surgery. CONCLUSION: The adductor canal block (ACB) has been demonstrated to be an effective method of reducing pain in patients undergoing total knee replacement (TKR) in the postoperative period. Nevertheless, despite the pronounced impact that ACB performed by an anesthesiologist under ultrasound guidance has on VAS scores according to intraoperative ACB by surgeons, its effect on clinical outcomes has not been demonstrated. TRIAL REGISTRATIONS: This study was retrospectively registered with the Clinical Trials Registry Platform on July 31, 2024 (NCT06533085).

Management of Refractory Cancer Pain with Intrathecal Drug Delivery and Spinal Cord Stimulation.

Background: Intrathecal pumps (ITPs) are indicated for refractory cancer pain and decrease systemic opioid requirements. While not yet indicated for cancer pain, spinal cord stimulators (SCSs) are used off-label for cancer pain, with increasing evidence of their efficacy. Materials and Methods: A retrospective chart review was conducted of patients who underwent both ITP and at least SCS trial for cancer pain. Primary outcomes were pain numeric rating scale (NRS) and daily morphine equivalents (MEQs). Results: Seventeen patients were identified. Both ITP and SCS were associated with significant decreases in pain ratings at the 3-month follow-up, but this decrease became nonsignificant subsequently. ITP, but not SCS, was associated with a significant decrease in MEQ. Conclusions: ITP and SCS may both provide efficacy for cancer pain, but the opioid-sparing effects of SCS may be limited. ITP and SCS may potentially be complementary in their ability to provide relief from cancer-related pain.

Perioperative opioids in high-risk children undergoing tonsillectomy - A single institution experience.

BACKGROUND: Patients undergoing tonsillectomy/ adenotonsillectomy (T/AT) can experience substantial postoperative pain. The aims of this study are to assess perioperative pain management in high-risk children (children with severe obstructive sleep apnea and other complex medical comorbidities or age younger than 2 years) undergoing T/AT, and the impact on oxygen levels and pain during extended Post-Anesthesia Care Unit (PACU) admission. METHODS: A retrospective case series study at a tertiary care children's hospital. RESULTS: There were 278 children enrolled in the study. The Apnea-Hypopnea index and mean oxygen nadir on preoperative polysomnography were 31.3 ± 25.76/h and 79.5 ± 9.5 % respectively. Overall, 246 (89 %) patients received intraoperative opioids alone (n = 35, 13 %) or in combination with non-opioid analgesia (n = 209, 75 %). While the median dose of opioid-free medications (acetaminophen, ibuprofen) ranged from 93 to 100 % of standard maximal dosing by weight and age, the median dose of opioids was significantly lower and ranged from 54 to 63 % of standard maximal dosing by weight and age, with 43 % of the patients receiving less than half the recommended maximum dose. Oxygen desaturation was charted in 21 patients (8 %) during their PACU admission. Patients who received opioid-free analgesia were as likely to develop oxygen desaturations (n = 17 (81 %) vs. n = 228 (89.4 %), p = 0.27) and to receive rescue pain medication during their PACU stay as patients who received opioids intraoperatively (n = 18 (56 %) vs. n = 167 (68 %), p = 0.23). CONCLUSIONS: Intraoperative pain management varies across high-risk pediatric tonsillectomies. Opioid-free analgesia was not associated with an increased need for pain medications during PACU admission, or with a decreased likelihood of oxygen desaturations compared to intra-operative opioid analgesia use.

Efficacy of subcutaneous sumatriptan in postcraniotomy pain and opioid consumption.

OBJECTIVE: Traditional pain management pathways following craniotomy are predicated on opioids. However, narcotics can confound critical neurological examination, contribute to respiratory depression, lower the seizure threshold, and lead to medication habituation, dependence, and/or abuse. Alternative medications to better address postoperative pain while mitigating opioid-related adverse effects remain insufficiently studied. Preliminary studies suggest sumatriptan, a 5-HT (1B/1D) receptor agonist known to regulate dural vasoactivity and inflammation, may moderate pain following trigeminal microvascular decompression and chronic postcraniotomy headache. In this study, the authors evaluated the efficacy of sumatriptan to modulate pain and opioid requirements following craniotomy surgery. METHODS: This was a single academic center, retrospective cohort study of 300 consecutive adult patients who underwent elective craniotomy surgery between 2015 and 2022. Patients were equally divided between a control and a sumatriptan cohort contingent upon administration of 6 mg of subcutaneous sumatriptan within 1 hour of surgery completion and prior to opioid administration. Postoperative opioid consumption at 6, 12, and 24 hours, as well as admission total, inpatient length of stay, and 30-day global reevaluation, were assessed. RESULTS: Three hundred patients were included for analysis. Significant differences were seen in baseline hypertension (p < 0.01), hyperlipemia (p < 0.01), anxiety (p = 0.04), and operative time (p = 0.02). A significant reduction of mean postoperative pain scores at 12 (p = 0.03) and 24 (p < 0.01) hours and total opioid consumption (p = 0.04) was observed in the sumatriptan cohort. Subgroup analysis revealed significantly lower postoperative pain scores at 6 (p = 0.05), 12 (p < 0.01), and 24 (p < 0.01) hours in patients who underwent burr hole placement in the sumatriptan cohort as compared with controls; however, no significant difference in opioid consumption was noted. No adverse events related to sumatriptan administration were noted throughout the study. CONCLUSIONS: Postoperative single-dose subcutaneous sumatriptan following elective craniotomy may reduce pain scores and opioid requirements. Additional studies are needed to better understand nuanced differences in opioid modulation and optimal patient selection.

A Review of the Literature on Episodes of Acute Fentanyl Intoxication in Pediatric Age and Toxicological Applications.

Fentanyl is an opioid with powerful analgesic effects and a high speed of action. Due to its pharmacological properties, this molecule has therapeutic application as an anesthetic in surgery or as palliative therapy for cancer patients. Unfortunately, in recent years, the easy availability of this substance, the low cost and the illegal online market have favored the large-scale diffusion of fentanyl. Fentanyl is available in different forms, including nasal spray, oral patches, soluble capsules, aerosol or the new version of fentanyl mixed with other drugs, making its use very widespread. Subjects of various ages are involved in fentanyl consumption, including minors that have not yet reached adolescence. In this work, we performed a literature review using the search engines PubMed NCBI and SCOPUS regarding episodes of acute fentanyl intoxication occurring in those of a pediatric age using the Mesh Terms "fentanyl" AND "overdose" AND "children". The inclusion criteria were English papers published in the last 10 years regarding the cases of children under the age of 10. We evaluated the most frequent methods of intake and the circumstances of such episodes. In cases of death, we analyzed the autopsy, the toxicological findings and the investigations carried out. The review results show that in this age group (under < 10 y.o. s), it is possible to identify the risk factors for fentanyl intake, such as the presence of this molecule within the family unit due to drug addiction or medical therapy. The results also demonstrate a significant risk of underestimation of this phenomenon, since the molecule is often not investigated through adequate toxicological analysis. These results, therefore, suggest always carrying out toxicological investigations in the case of suspected fentanyl intoxication, both on patients or cadavers. The investigations must always include a urinary screening for opiates, and the request for a second level analysis with molecule dosage in cases of positivity or in cases of strong suspicion for assumption. In cases of intoxication in a family context of drug addiction, it is necessary to investigate the chronicity of the intake through hair analysis and evaluate the possible co-administration of other drugs. In conclusion, we suggest a protocol, applicable both on patients or cadavers, which can be useful for physicians and forensic pathologists in order to promptly identify these cases and allow for the reporting of them to the judicial authorities with the adoption of strict prevention and control measures.

Direct effects of heroin and methadone on T cell function.

Opioid addiction presents a relevant health challenge, with chronic heroin use linked to detrimental effects on various aspects of physical, mental, and sociological health. Opioid maintenance therapy (OMT), particularly using methadone, is the primary treatment option for heroin addiction. Previous studies using blood samples from current heroin addicts and OMT patients have shown immunomodulatory effects of heroin and methadone on T cell function. However, various additional factors beyond heroin and methadone affect these results, including the consumption of other substances, a stressful lifestyle, comorbid psychological and somatic disorders, as well as additional medications. Therefore, we here investigated the direct effects of heroin and methadone on purified human T cells in vitro. Our results reveal that both, heroin and methadone directly suppress Tcell activation and proliferation. Strikingly, this inhibitory effect was markedly stronger in the presence of methadone, correlating with a decrease in secretion of pro-inflammatory cytokines. While heroin did not interfere with the in vitro differentiation and expansion of regulatory Tcells (Tregs), methadone significantly impaired the proliferation of Tregs. Overall, our findings suggest a direct inhibitory impact of both opioids on effector T cell function in vitro, with methadone additionally interfering with Treg induction and expansion in contrast to heroin.

Evolution of Fentanyl Prescription Patterns and Administration Routes in Primary Care in Salamanca, Spain: A Comprehensive Analysis from 2011 to 2022.

(1) Background: The escalating use of opioids contributes to social, health, and economic crises. In Spain, a notable surge in the medical prescription of opioids in recent years has been observed. The aim of this work was to assess the consumption rate of fentanyl, categorised by the different administration routes, in Primary Care in the province of Salamanca (Spain) spanning the years 2011 to 2022, and to compare it with the national trend and with data from the US. (2) Methods: Doses per inhabitant per day (DHD) were calculated, and interannual variations, as well as consumption rates, were subject to thorough analysis. (3) Results: The prevalence of fentanyl use in Salamanca has doubled from 1.21 DHD in 2011 to 2.56 DHD in 2022, with the transdermal system (TD) as the predominant administration route. This upward trajectory mirrors the national trend, yet the rise in fentanyl use is markedly lower than the reported data in the US. This finding may be attributed to an ageing population and potentially inappropriate fentanyl prescriptions, i.e., for the management of chronic non-cancer pain and other off-label prescriptions. (4) Conclusions: The use of fentanyl in Salamanca, particularly through transdermal systems, doubled from 2011 to 2022, aligning with the national trend. Preventive measures are imperative to prevent fentanyl misuse and moderate the observed escalation in consumption rates.

Determinants of successful opioid deprescribing: Insights from French pain physicians-A qualitative study.

BACKGROUND: Long-term use of opioids does not result in significant clinical improvement and has shown more adverse than beneficial effects in chronic pain conditions. When opioids cause more adverse effects than benefits for the patient, it may be necessary to initiate a process of deprescribing. AIM: To explore the perceptions of French pain physicians regarding the process of opioid deprescribing in patients experiencing chronic non-cancer and to generate an understanding of the barriers and levers to the deprescribing process. METHODS: We conducted a multicentric observational study with qualitative approach. Individual semi-structured interviews exploring pain physicians' perceptions, beliefs, and representations to assess the determinants of opioid deprescribing with an interview guide were used. After checking the transcripts, an inductive and independent thematic analysis of the interviews was to extract meaningful themes from the dataset. RESULTS: Twelve pain physicians were interviewed. The main obstacles to deprescribing revolved around patient-specific attributes, characteristics of the opioids themselves, and limitations within the current healthcare system, that hinder optimal patient management. Conversely, patient motivation and education, recourse to hospitalization in a Pain Department with multidisciplinary care, follow-up by the general practitioner, and training and information dissemination among patients and clinicians emerged as facilitative elements for opioid deprescribing. CONCLUSION: This study underscores the needs to improve the training of healthcare professionals, the effective communication of pertinent information to patients, and the establishment of a therapeutic partnership with the patient. It is therefore essential to carry out the deprescribing process in a collaborative and interprofessional manner, encompassing both pharmaceutical and non-pharmaceutical strategies.

Protective or potentially harmful? Altering drug consumption behaviors in response to xylazine adulteration.

Background: Xylazine is an increasingly common adulterant in the North American unregulated drug supply that is associated with adverse health outcomes (e.g., skin infections, overdose). However, there are significant knowledge gaps regarding how xylazine was initially identified and how syringe services program (SSP) staff and clients (people who use drugs) responded to its emergence. Methods: From June-July 2023, we conducted qualitative interviews with medical (e.g., clinicians) and frontline SSP staff (e.g., outreach workers) and adult clients with a history of injection drug use at a Miami-based SSP. Inductive memos identified emergent codes; thematic analysis involving team consensus established final themes. Results: From interviews with SSP staff (n = 8) and clients (n = 17), xylazine emergence was identified at different times, in various ways. Initially, during summer 2022, clients identified a "tranquilizer-like substance" that worsened sedation and withdrawal and caused wounds. SSP medical staff later identified this adulterant as xylazine by treating new medical cases and through diverse information-sharing networks that included professional societies and news sources; however, frontline SSP staff and clients needed additional educational resources about xylazine and its side effects. With limited guidance on how to reduce harm from xylazine, SSP clients altered their drug consumption routes, reduced drug use, and relied on peers' experiences with the drug supply to protect themselves. Some individuals also reported preferring xylazine-adulterated opioids and increasing their drug use, including the use of stimulants to avoid over sedation. Conclusions: Xylazine's emergence characterizes the current era of unprecedented shifts in the unregulated drug supply. We found that xylazine spurred important behavioral changes among people who use drugs (e.g., transitioning from injecting to smoking). Incorporating these experiences into early drug warning surveillance systems and scaling up drug-checking services and safer smoking supply distribution could help mitigate significant health harms caused by xylazine and other emergent adulterants.

Evaluation of Postoperative Pain When Adding a Tibial Nerve Block to the Femoral Nerve Block for Total Knee Arthroplasty.

Background: The aim of this study was to compare the postoperative analgesic efficacy when a tibial nerve block was added to the femoral nerve block for total knee arthroplasty (TKA). Methods: A total of 60 patients were randomly assigned to the experimental group (EG) or the control group (CG) in a 1:1 ratio. The thirty patients who formed the CG underwent an ultrasound-guided femoral nerve block together with neuraxial anaesthesia and the administration of opioids and NSAIDs through an intravenous elastomeric pump for the management of the postoperative pain; the other thirty, who formed the EG, underwent neuraxial anaesthesia together with femoral and tibial nerve blocks. The efficacy of the analgesic effect was evaluated based on the numerical pain rating scale (NPRS) and on the need for analgesic rescue at different time intervals within 48 h after surgery. Results: At 24 h, the mean NPRS score in the EG and CG at rest was 1.50 ± 1.19 and 1.63 ± 1.60 [U = 443.5, p = 0.113], respectively. With joint movement, the mean NPRS score was 2.80 ± 1.49 and 3.57 ± 1.79 [U = 345, p = 0.113], respectively. Ten patients in the EG [33.3%] and 24 in the CG [80%] required rescue analgesia [Phi = 0.471, p < 0.001]. At 48 h, the mean NPRS score in the EG and CG at rest was 0.33 ± 0.60 and 0.43 ± 0.72 [U = 428, p = 0.681], respectively. With movement, the mean NPRS score was 1.03 ± 0.99 in the EG and 1.60 ± 1.07 in the CG [U = 315, p = 0.038]. No patient in the EG group required rescue analgesia, while three patients in the CG [10%] did [Phi = 0.229, p = 0.076]. The mean opioid dosage in the CG was 300 mg, whereas in the EG it was 40 mg ± 62.14 [U < 0.05, p < 0.001]. Conclusions: Adding a tibial nerve block to the femoral nerve block in TKA may achieve the same analgesic efficacy within 48 h after surgery and would reduce the systematic use of opioids.

Influence of aging on opioid dosing for perioperative pain management: a focus on pharmacokinetics.

The older population continues to grow in all countries, and surgeons are encountering older patients more frequently. The management of postoperative pain in older patients can be a difficult task. Opioids are the mainstay of perioperative pain control. This paper assesses some pharmacokinetic age-related aspects and their relationship with the use of opioids in the perioperative period. Changes in body composition and organ function, and pharmacokinetics in older patients, as well as characteristics of opioids commonly used in the perioperative period are described. Specific problems, dose titration, and patient-controlled analgesia in the elderly are also reviewed. Opioids can be safety used in perioperative period, even in the elderly. The choice of drugs and doses can be individualized according to the surgery, opioid pharmacokinetics, comorbidities, and routes of administration.

Nudging to assist opioid tapering among chronic non-malignant pain patients: A systematic scoping review.

Objectives: Use of opioids can lead to frequent and severe side effects, prompting the exploration of non-pharmacological alternatives, including nudging, to reduce opioid consumption. This review identifies and evaluates patient-targeted nudges to support opioid tapering among adults with chronic non-cancer pain. Methods: We searched EMBASE, MEDLINE, CINAHL, PsycInfo, and Social Science citation index for articles published from 2010 to January 2023. Eligibility criteria were based on the PICOS framework and included original peer-reviewed English language studies on adults with chronic non-cancer pain and interventions aligning with the nudge definition by Thaler and Sunstein. Studies with relevant comparators, measurable outcomes, real-world data, and pre/post-intervention measures were included. Data were manually extracted and reported in a descriptive manner. The process adhered to PRISMA-ScR reporting guidelines. Results: Four of 222 articles fulfilled the inclusion criteria. All included nudges aimed at providing information to support decision-making and behavior change. Three nudge categories were identified: increasing salience, understanding mappings, and feedback. Outcome measures were program-related, focusing on perceptions, knowledge acquisition, engagement metrics, and psychological well-being. Conclusions: There were no statistically significant effects or only small evidence of effects in the program-related outcomes. None of the studies included a control group with standard care or no intervention comparison and none included objective measures of opioid reduction. More studies are needed to draw conclusions on the effectiveness of nudges to support opioid tapering among chronic non-cancer pain patients.

Perioperative Short-Term Glucocorticoids Do Not Increase Incidence of Complications after Total Joint Arthroplasty in Patients with Rheumatoid Arthritis.

OBJECTIVES: The safety and analgesic efficacy of perioperative glucocorticoids have been established for patients without rheumatoid arthritis. Therefore, our study aims to investigate whether similar benefits can be observed in patients with rheumatoid arthritis undergoing total joint arthroplasty. Specifically, we aim to explore the impact of perioperative glucocorticoid use on postoperative complications, opioid consumption, incidence of hypotension, hyperglycemia, 30-day mortality, and 90-day re-admission in this patient population. METHODS: Approval for the study protocol was obtained from the Medical Research Ethics Committee at Sichuan University, aligning with the principles outlined in the Declaration of Helsinki. We retrospectively analyzed a consecutive series of patients with rheumatoid arthritis who underwent total joint arthroplasty at our medical center between November 2009 and April 2021 and who were not on chronic glucocorticoid therapy before surgery. Those who received glucocorticoids at any time during hospitalization were compared to those who did not in terms of acute complications within 90 days after surgery as well as postoperative rescue opioid consumption, hypotension, and hyperglycemia during hospitalization. The two groups were also compared in terms of overall duration of hospitalization, all-cause mortality within 30 days, and readmission for any reason within 90 days. Continuous data were assessed for significance using the independent-samples t test. Categorical data were assessed using the Pearson chi-squared test. RESULTS: Of the 849 patients included in the analysis, 598 administered perioperative glucocorticoids and 251 did not. Prior to surgery, the two groups did not differ significantly in any clinicodemographic variable that we examined. The incidence of acute postoperative complications (2.3% vs. 4.0%, p = 0.187) and acute postoperative infection (2.0% vs. 2.8%, p = 0.482) was comparable between those who received perioperative glucocorticoids and those who did not, but the former group exhibited a significantly lower incidence of rescue opioid use (17.9% vs. 44.6%, p < 0.001) as well as significantly lower total rescue opioid consumption (4.7 ± 2.1 mg vs. 8.9 ± 4.6 mg, p < 0.001). However, the two groups showed similar incidences of postoperative hypotension, hyperglycemia, 30-day mortality, and 90-day re-admission. CONCLUSION: Perioperative glucocorticoids may reduce the need for rescue opioids after total joint arthroplasty of rheumatoid arthritis patients, without increasing the incidence of acute complications, hypotension or hyperglycemia.

Preoperative Opioid Use Increases Postoperative Opioid Demand, but Not Length of Stay After Spine Trauma Surgery.

BACKGROUND: Preoperative opioid use has been well-studied in elective spinal surgery and correlated with numerous postoperative complications including increases in immediate postoperative opioid demand (POD), continued opioid use postoperatively, prolonged length of stay (LOS), readmissions, and disability. There is a paucity of data available on the use of preoperative opioids in surgery for spine trauma, possibly because there are minimal options for opioid reduction prior to emergent spinal surgery. Nevertheless, patients with traumatic spinal injuries are at a high risk for adverse postoperative outcomes. This study investigated the effects of preoperative opioid use on POD and LOS in spine trauma patients. METHODS: 130 patients were grouped into two groups for primary comparison: Group 1 (preoperative opioid use, N = 16) and Group 2 (no opioid use, N = 114). Two subgroups of Group 2 were used for secondary analysis against Group 1: Group 3 (no substance abuse, N = 95) and Group 4 (other substance abuse, N = 19). Multivariable analysis was used to determine if there were significant differences in POD and LOS. RESULTS: Primary analysis demonstrated that preoperative opioid users required an estimated 97.5 mg/day more opioid medications compared to non-opioid users (P < 0.001). Neither primary nor secondary analysis showed a difference in LOS in any of the comparisons. CONCLUSIONS: Preoperative opioid users had increased POD compared to non-opioid users and patients abusing other substances, but there was no difference in LOS. We theorize the lack of difference in LOS may be due to the enhanced perioperative recovery protocol used, which has been demonstrated to reduce LOS.

"It frees your body from that pain thought": A mixed-methods exploration of patterns, contexts, and experiences of cannabis use for pain in rural communities.

U.S. adults increasingly report using cannabis to manage chronic pain and rural areas have inadequate comprehensive pain management. Using mixed methods, we aimed to understand how and why some rural adults use cannabis for pain, including within the context of co-use with opioids. Participants (N = 14, Oklahoma) were rural-dwelling adults who used tobacco and ≥1 other substance, including cannabis and opioids, ≥3 days per week. Participants completed 14 days of ecological momentary assessment (EMA) regarding substance use and subsequent in-depth interviews discussing maps of their substance use reports. Half (7/14) described cannabis use for chronic pain, and most of these (85%) reported use on ≥75% of EMA days. The most frequently reported cannabis use motive was therapeutic/medicinal (90% of use reports). Most reports were of combusted cannabis (88% of use reports) at home (99% of use reports). Same-day use of cannabis and opioids was relatively common (45% of daily surveys), but seemingly not within close temporal proximity. Interview narratives characterized cannabis as modifying pain-adjacent factors (eg, thoughts), not eliminating pain itself. They recounted using a repertoire of substances to manage different pain dimensions (eg, intensity, quality) and balance perceived trade-offs of different substances. Participants described high medical cannabis access, low pain specialist access, and most physicians as unwilling to discuss cannabis for pain. The findings suggest that rural-dwelling patients could benefit from increased access to comprehensive pain management, having cannabis addressed within pain management provider discussions, and that risks and benefits of cannabis use for pain must be better established. PERSPECTIVE: This study used a geographically explicit EMA mixed method to gather rich, intensive pilot data on cannabis use and co-use for chronic pain in rural Oklahoma. It provides unique insights to inform future research on cannabis use among a vulnerable and understudied subgroup of adults with pain-rural residents.

Opioid Use and Gut Dysbiosis in Cancer Pain Patients.

Opioids are commonly used for the management of severe chronic cancer pain. Their well-known pharmacological effects on the gastrointestinal system, particularly opioid-induced constipation (OIC), are the most common limiting factors in the optimization of analgesia, and have led to the wide use of laxatives and/or peripherally acting mu-opioid receptor antagonists (PAMORAs). A growing interest has been recently recorded in the possible effects of opioid treatment on the gut microbiota. Preclinical and clinical data, as presented in this review, showed that alterations of the gut microbiota play a role in modulating opioid-mediated analgesia and tolerability, including constipation. Moreover, due to the bidirectional crosstalk between gut bacteria and the central nervous system, gut dysbiosis may be crucial in modulating opioid reward and addictive behavior. The microbiota may also modulate pain regulation and tolerance, by activating microglial cells and inducing the release of inflammatory cytokines and chemokines, which sustain neuroinflammation. In the subset of cancer patients, the clinical meaning of opioid-induced gut dysbiosis, particularly its possible interference with the efficacy of chemotherapy and immunotherapy, is still unclear. Gut dysbiosis could be a new target for treatment in cancer patients. Restoring the physiological amount of specific gut bacteria may represent a promising therapeutic option for managing gastrointestinal symptoms and optimizing analgesia for cancer patients using opioids.

Naltrexone accelerated oral traumatic ulcer healing and downregulated TLR-4/NF-kB pathway in Wistar rats.

OBJECTIVE: To assess the effect of naltrexone on oral mucosal healing using a traumatic ulcer model DESIGN: Wistar rats (n = 112) received distilled water (control) or naltrexone (0.5, 10, or 50 mg/kg/day). Ulcers were induced on the buccal mucosa using a round skin biopsy punch (diameter 6 mm). Euthanasia was performed on days 1, 3, 7, and 14. Healing was assessed by ulcer area, histological scores, histomorphometric analysis (number of polymorphonuclears, mononuclears, and fibroblasts), and collagen percentage. Immunohistochemistry for TLR-2, TLR-4, NF-kB, and CD31 was evaluated. Nociceptive threshold was measured daily. RESULTS: The 50 mg/kg group showed reduced ulcer area on days 1 (p < 0.001), 3 (p < 0.05), and 14 (p < 0.01). In this group, there was, on day 14, an increase in the percentage of reepithelization (p = 0.043) and collagen (p < 0.05), an increase in connective tissue maturation (p = 0.016), and on day 7 an increase in fibroblasts (p < 0.001). The 10 mg/kg dose reduced the ulcer area on day 1 (p < 0.001). The 50 mg/kg group showed lower expression of TLR-4 (p < 0.001) on day 1, NF-kB on days 1 (p < 0.05) and 14 (p < 0.05), and CD31 on day 14 (p < 0.05). The 0.5 and 10 mg/kg doses reduced TLR-4 expression on day 1 (p < 0.05; p < 0.01, respectively). Nociceptive threshold increased in the 50 mg/kg group (p < 0.01). CONCLUSION: Naltrexone enhanced traumatic oral ulcer healing by reducing TLR-4/NF-kB signaling and promoting fibroblast proliferation and collagen deposition. Additionally, naltrexone reduced pain in rats.