Effect of fentanyl and remifentanil on neuron damage and oxidative stress during induction neurotoxicity.

Opioids can be used for medical and non-medical purposes. Chronic pain such as cancer, as well as the frequent use of such drugs in places such as operating rooms and intensive care units, and in non-medical areas like drug abuse the effects and side effects of these drugs need to be examined in more detail. For this purpose, the effects of fentanyl and remifentanil drugs on neuroinflammation, oxidative stress and cholinesterase metabolism were investigated. Neuron cells (CRL-10742) were used for the evaluation of the toxicity of fentanyl and remifentanil. MTT, PON1 activity and total thiol levels for its effect on oxidative stress, AChE and BChE activities for its effect on the cholinergic system, and TNF, IL-8 and IL-10 gene levels for its neuroinflammation effect were determined. The highest neurotoxic dose of fentanyl and remifentanil was determined as 10 µg/mL. It was observed that the rate of neuron cells in this dose has decreased by up to 61.80% and 56.89%, respectively. The IL-8 gene expression level in both opioids was down-regulated while IL 10 gene level was up-regulated in a dose-dependent manner compared to the control. In our results, the TNF gene expression level differs between the two opioids. In the fentanyl group, it was seen to be up-regulated in a dose-dependent manner compared to the control. Fentanyl and remifentanil showed an inhibitory effect against PON1, while remifentanil showed an increase in total thiol levels. PON1, BChE and total thiol activities showed similarity with MTT.

Impact of prescribed opioid use on development of dementia among patients with chronic non-cancer pain.

We aimed to examine the association between opioid use and the development of dementia in patients with chronic non-cancer pain in South Korea. Data were extracted from the National Health Insurance Service database in South Korea. Adult patients diagnosed with musculoskeletal diseases with chronic non-cancer pain between 2010 and 2015 were included in the analysis. Patients who were prescribed opioids regularly and continuously for ≥ 90 days were classified as opioid users. In total, 1,261,682 patients with chronic non-cancer pain were included in the final analysis, of whom 21,800 (1.7%) were opioid users. From January 1, 2016 to December 31, 2020, 35,239 (2.8%) patients with chronic non-cancer pain were newly diagnosed with dementia. In the multivariable model, opioid users showed a 15% higher risk of developing dementia than the control group. Additionally, opioid users showed a 15% and 16% higher risk of developing Alzheimer's disease and unspecified dementia, respectively, than the control group, but did not show any significant differences for vascular dementia. Among adult patients with chronic non-cancer pain, opioid users were at a higher risk of developing dementia than the control group; the risk was significantly higher for Alzheimer's disease but not for vascular dementia in this study. Our results suggest that in patients with CNCP, public health strategies should target opioid users for early dementia detection and intervention.

Trajectories of prescription opioid tapering in patients with chronic non-cancer pain: a retrospective cohort study, 2015-2020.

OBJECTIVE: To identify common opioid tapering trajectories among patients commencing opioid taper from long-term opioid therapy for chronic non-cancer pain and to examine patient-level characteristics associated with these different trajectories. DESIGN: A retrospective cohort study. SETTING: Australian primary care. SUBJECTS: Patients prescribed opioid analgesics between 2015 and 2020. METHODS: Group-based trajectory modeling and multinomial logistic regression analysis were conducted to determine tapering trajectories and to examine demographic and clinical factors associated with the different trajectories. RESULTS: A total of 3369 patients commenced a taper from long-term opioid therapy. Six distinct opioid tapering trajectories were identified: low dose / completed taper (12.9%), medium dose / faster taper (12.2%), medium dose / gradual taper (6.5%), low dose / noncompleted taper (21.3%), medium dose / noncompleted taper (30.4%), and high dose / noncompleted taper (16.7%). A completed tapering trajectory from a high opioid dose was not identified. Among patients prescribed medium opioid doses, those who completed their taper were more likely to have higher geographically derived socioeconomic status (relative risk ratio [RRR], 1.067; 95% confidence interval [CI], 1.001-1.137) and less likely to have sleep disorders (RRR, 0.661; 95% CI, 0.463-0.945) than were those who didn't complete their taper. Patients who didn't complete their taper were more likely to be prescribed strong opioids (eg, morphine, oxycodone), regardless of whether they were tapered from low (RRR, 1.444; 95% CI, 1.138-1.831) or high (RRR, 1.344; 95% CI, 1.027-1.760) doses. CONCLUSIONS: Those prescribed strong opioids and high doses appear to be less likely to complete tapering. Further studies are needed to evaluate the clinical outcomes associated with the identified trajectories.

Clinical Practice Guidelines for Cannabis and Cannabinoid-Based Medicines in the Management of Chronic Pain and Co-Occurring Conditions.

Background: One in five individuals live with chronic pain globally, which often co-occurs with sleep problems, anxiety, depression, and substance use disorders. Although these conditions are commonly managed with cannabinoid-based medicines (CBM), health care providers report lack of information on the risks, benefits, and appropriate use of CBM for therapeutic purposes. Aims: We present these clinical practice guidelines to help clinicians and patients navigate appropriate CBM use in the management of chronic pain and co-occurring conditions. Materials and Methods: We conducted a systematic review of studies investigating the use of CBM for the treatment of chronic pain. Articles were dually reviewed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Clinical recommendations were developed based on available evidence from the review. Values and preferences and practical tips have also been provided to support clinical application. The GRADE system was used to rate the strength of recommendations and quality of evidence. Results: From our literature search, 70 articles met inclusion criteria and were utilized in guideline development, including 19 systematic reviews and 51 original research studies. Research typically demonstrates moderate benefit of CBM in chronic pain management. There is also evidence for efficacy of CBM in the management of comorbidities, including sleep problems, anxiety, appetite suppression, and for managing symptoms in some chronic conditions associated with pain including HIV, multiple sclerosis, fibromyalgia, and arthritis. Conclusions: All patients considering CBM should be educated on risks and adverse events. Patients and clinicians should work collaboratively to identify appropriate dosing, titration, and administration routes for each individual. Systematic Review Registration: PROSPERO no. 135886.

Baseline Characteristics From a New Longitudinal Cohort of Patients With Noncancer Pain and Chronic Opioid Use in the United States.

Retrospective cohort studies have consistently observed that long-term prescription opioid use is a risk factor for new major depressive episodes. However, prospective studies are needed to confirm these findings and establish evidence for causation. The Prescription Opioids and Depression Pathways cohort study is designed for this purpose. The present report describes the baseline sample and associations between participant characteristics and odds of daily versus nondaily opioid use. Second, we report associations between participant characteristics and odds of depression, dysthymia, anhedonia, and vital exhaustion. Patients with noncancer pain were eligible if they started a new period of prescription opioid use lasting 30 to 90 days. Participants were 54.8 (standard deviation ± 11.3) years of age, 57.3% female and 73% White race. Less than college education was more common among daily versus nondaily opioid users (32.4% vs 27.3%; P = .0008), as was back pain (64.2% vs 51.3%; P < .0001), any nonopioid substance use disorder (12.8% vs 4.8%; P < .0001), and current smoking (30.7% vs 18.4% P < .0001). High pain interference (50.9% vs 28.4%; P < .0001) was significantly associated with depression, as was having more pain sites (6.9 ± 3.6 vs 5.7 ± 3.6; P < .0001), and benzodiazepine comedication (38.2% vs 23.4%; P < .0001). High pain interference was significantly more common among those with anhedonia (46.8% vs 27.4%; P < .0001), and more pain sites (7.0 ± 3.7 vs 5.6 ± 3.6; P < .0001) were associated with anhedonia. Having more pain sites (7.9 ± 3.6 vs 5.5 ± 3.50; P < .0001) was associated with vital exhaustion, as was back pain (71.9% vs 56.8%; P = .0001) and benzodiazepine comedication (42.8% vs 22.8%; P < .0001). Patients using prescription opioids for noncancer pain have complex pain, psychiatric, and substance use disorder comorbidities. Longitudinal data will reveal whether long-term opioid therapy leads to depression or other mood disturbances such as anhedonia and vital exhaustion. PERSPECTIVE: This study reports baseline characteristics of a new prospective, noncancer pain cohort study. Risk factors for adverse opioid outcomes were most common in those with depression and vital exhaustion and less common in dysthymia and anhedonia. Baseline data highlight the complexity of patients receiving long-term opioid therapy for noncancer pain.

A neural circuit associated with anxiety-like behaviors induced by chronic inflammatory pain and the anxiolytic effects of electroacupuncture.

AIMS: Negative emotions induced by chronic pain are a serious clinical problem. Electroacupuncture (EA) is a clinically proven safe and effective method to manage pain-related negative emotions. However, the circuit mechanisms underlying the effect of EA treatment on negative emotions remain unclear. METHODS: Plantar injection of complete Freund's adjuvant (CFA) was performed to establish a rat model of chronic inflammatory pain-induced anxiety-like behaviors. Adeno-associated virus (AAV) tracing was used to identify excitatory synaptic transmission from the rostral anterior cingulate cortex (rACC) to the dorsal raphe nucleus (DRN). Employing chemogenetic approaches, we examined the role of the rACC-DRN circuit in chronic pain-induced anxiety-like behaviors and investigated whether EA could reverse chronic pain-induced dysfunctions of the rACC-DRN circuit and anxiety-like behaviors. RESULTS: We found that chemogenetic activation of the rACC-DRN circuit alleviated CFA-induced anxiety-like behaviors, while chemogenetic inhibition of the rACC-DRN circuit resulted in short-term CFA-induced anxiety-like behaviors. Further research revealed that the development of CFA-induced anxiety-like behaviors was attributed to the dysfunction of rACC CaMKII neurons projecting to DRN serotonergic neurons (rACCCaMKII-DRN5-HT neurons) but not rACC CaMKII neurons projecting to DRN GABAergic neurons (rACCCaMKII-DRNGABA neurons). This is supported by the findings that chemogenetic activation of the rACCCaMKII-DRN5-HT circuit alleviates anxiety-like behaviors in rats with chronic pain, whereas neither chemogenetic inhibition nor chemogenetic activation of the rACCCaMKII-DRNGABA circuit altered CFA chronic pain-evoked anxiety-like behaviors in rats. More importantly, we found that EA could reverse chronic pain-induced changes in the activity of rACC CaMKII neurons and DRN 5-HTergic neurons and that chemogenetic inhibition of the rACCCaMKII-DRN5-HT circuit blocked the therapeutic effects of EA on chronic pain-induced anxiety-like behaviors. CONCLUSIONS: Our data suggest that the reversal of rACCCaMKII-DRN5-HT circuit dysfunction may be a mechanism underlying the therapeutic effect of EA on chronic pain-induced anxiety-like behaviors.

Should We Use COMM (Current Opioid Misuse Measure) to Screen for Opioid Abuse in Patients With Cancer Pain?

BACKGROUND: Growing concerns about opioid use disorder (OUD) and the resulting decrease in opioid availability for patients with cancer pain highlight the need for reliable screening tools to identify the subset of patients at increased risk for aberrant opioid use. Our study examines the utility of Current Opioid Misuse Measure (COMM) recommended by the NCCN Clinical Practice Guidelines in Oncology for Adult Cancer Pain. PATIENTS AND METHODS: We analyzed prospectively collected patient-reported outcomes of 444 consecutive patients with cancer seen in pain clinics of a cancer center at 2 time points within 100 days. The relationship of COMM to other OUD screening tools, pain, opioid doses, patient demographics, and mortality was examined using univariate and multivariable logistic regression. We also examined individual items of COMM for face validity. RESULTS: Among 444 patients who completed pain surveys at 2 time points, 157 (35.4%) did not complete COMM surveys. Using a COMM cutoff of ≥13, a total of 84 patients (29.3%; 84/287) scored positive for aberrant drug use. As patients remained on opioids for 49 to 100 days, the likelihood of improving COMM score (turning from positive to negative) was 6.1 times greater than the reverse. The number of patients with COMM ≥13 was 3.8 times higher than the number of patients with CPT diagnostic codes for OUD, 5.3 times higher than those with a positive urine drug screening, and 21 times higher than those with a positive CAGE (Cut Down, Annoyed, Guilty, Eye-Opener Questionnaire) score. COMM ≥13 was not associated with pain relief response (worst pain intensity score ≥2 points on the Brief Pain Inventory), opioid doses, gender, or age. Contrary to the intended use of COMM to identify aberrant opioid use, COMM ≥13 predicted mortality: patients with COMM ≥13 were 1.9 times more likely to die within 12 months. CONCLUSIONS: Our study found that using COMM in a cancer population may significantly overestimate the risk of opioid misuse. Using COMM without modifications can create an additional barrier to cancer pain management, such as limiting appropriate opioid use.

Intravenous Methadone for Perioperative and Chronic Cancer Pain: A Review of the Literature.

Intravenous methadone may be useful in acute and chronic pain management compared with other opioids because of its pharmacokinetic and pharmacodynamic characteristics, including the long duration of effect and ability to modulate both pain stimuli propagation and analgesic descending pathways. However, methadone is underused in pain medicine because of several misperceptions. A review of studies was performed to assess data regarding the use of methadone in perioperative pain and chronic cancer pain. The majority of studies have shown that intravenous methadone produces an effective postoperative analgesia and lowers opioid consumption in the postoperative period, without more adverse effects in comparison with other opioid analgesics, and has an interesting potential to prevent persistent postoperative pain. A minority of studies investigated the use of intravenous methadone for cancer pain management. These studies were mostly case series that showed promising activities of intravenous methadone for difficult pain conditions. There is sufficient evidence suggesting that intravenous methadone is effective in perioperative pain, while more studies are needed in patients with cancer pain.

Patients' Perspectives on the Development of Prescription Opioid Use Disorder in Patients with Chronic Non-Cancer Pain.

INTRODUCTION: In the past decade, prescription opioid use increased exponentially and concomitantly opioid use disorders (OUD) are becoming more common. Several risk factors for developing OUD have been identified, but little is known regarding the patients' perspective on developing a prescription OUD. METHODS: We recruited 25 adults undergoing treatment for prescription OUD. In-depth, semi-structured interviews focussed on experiences with long-term opioid use, knowledge and attitudes regarding opioids, and access to opioids. A directed content analysis was conducted on the transcribed interviews using NVivo. RESULTS: Participants showed that the development of an OUD is affected by various factors which could be grouped into three themes: (1) experiences driving initiation, (2) experiences driving continuation, and (3) experiences with prescription OUD. Besides the need for pain management, the dynamics of patient-provider communication, care coordination, provider vigilance, and environmental support all contributed to the way patients used their opioids. CONCLUSION: Patients' experiences illustrate that the first stage of the development of prescription OUD differs from the development of other substance addictions. Negative reinforcement might play a more prominent role in the early phase of prescription opioid use. Patients expressed a lack of guidance, both at the start of use and long-term use, easy access to new prescriptions and a lack of monitoring as main drivers of the development. Poorly controlled pain and subjective stress fuelled continuous opioid use.

Association of OPRM1, MIR23B, and MIR107 genetic variability with acute pain, chronic pain and adverse effects after postoperative tramadol and paracetamol treatment in breast cancer.

BACKGROUND: Tramadol is an opioid analgesic often used for pain management after breast cancer surgery. Its analgesic activity is due to the activation of the µ-opioid receptor, encoded by the OPRM1 gene. This study investigated the association of genetic variability in OPRM1 and its regulatory miRNA genes with outcomes of tramadol/paracetamol treatment after breast cancer surgery with axillary lymphadenectomy. PATIENTS AND METHODS: The study included 113 breast cancer patients after breast cancer surgery with axillary lymphadenectomy treated with either 75/650 mg or 37.5/325 mg of tramadol with paracetamol for pain relief within the randomized clinical trial KCT 04/2015-DORETAonko/si at the Institute of Oncology Ljubljana. All patients were genotyped for OPRM1 rs1799971 and rs677830, MIR23B rs1011784, and MIR107 rs2296616 using competitive allele-specific PCR. The association of genetic factors with acute and chronic pain as well as adverse effects of tramadol treatment was evaluated using logistic regression, Fisher's exact test, and Mann-Whitney test. RESULTS: The investigated OPRM1 related polymorphisms were not associated with acute pain assessed with the VAS scale within four weeks after surgery (all P > 0.05). Carriers of at least one polymorphic OPRM1 rs1799971 allele had a higher risk of constipation in the first four weeks after surgery compared to non-carriers (OR = 4.5, 95% CI = 1.6-12.64, P = 0.004). Carriers of at least one polymorphic OPRM1 rs677830 allele had a higher risk of constipation after third week of tramadol treatment (OR = 3.11, 95% CI = 1.08-8.89, P = 0.035). Furthermore, carriers of two polymorphic MIR23B rs1011784 alleles had a higher risk of nausea after 28 days of tramadol treatment (OR = 7.35, 95% CI = 1.27-42.6, P = 0.026), while heterozygotes for MIR107 rs2296616 allele had a lower risk of nausea after 21 days of tramadol treatment (OR = 0.21, 95% CI = 0.05-0.87, P = 0.031). In carriers of two polymorphic MIR107 rs2296616 alleles, chronic pain was significantly more common than in carriers of two wild-type alleles (P = 0.004). Carriers of at least one polymorphic MIR23B rs1011784 allele experienced more neuropathic pain after adjustment for tramadol dose (OR = 2.85, 95% CI = 1.07-7.59, P = 0.036), while carriers of at least one polymorphic OPRM1 rs677830 allele experienced less neuropathic pain compared to carriers of two wild-type alleles (OR = 0.38, 95% CI = 0.15-0.99, P = 0.047). CONCLUSIONS: Genetic variability of OPRM1 and genes coding for miRNAs that could affect OPRM1 expression may be associated with adverse effects of tramadol/paracetamol treatment as well as with chronic and neuropathic pain after breast cancer surgery with axillary lymphadenectomy.

Association between sustained opioid prescription and frequent emergency department use: a cohort study.

BACKGROUND: Chronic non-cancer pain (CNCP) is common among frequent emergency department (ED) users, although factors underlying this association are unclear. This study estimated the association between sustained opioid use and frequent ED use among patients with CNCP. METHODS: Retrospective cohort study using a Canadian provincial health insurer database (Régie d'Assurance Maladie du Québec). The database included adults with both ≥1 chronic condition and ≥ 1 ED visit in 2012 or 2013. Inclusion in the study further required a CNCP diagnosis, public drug insurance coverage and 1-year survival after the first ED visit in 2012 or 2013 (index visit). Multivariable logistic regression was used to derive ORs of frequent ED use (≥5 visits in the year following the index visit) subsequent to sustained opioid use (≥60 days opioids prescription within 90 days preceding the index visit), adjusting for important covariables. RESULTS: From 576 688 patients in the database, 58 237 were included in the study. Of these, 4109 (7.1%) had received a sustained opioid prescription and 4735 (8.1%) were frequent ED users in the follow-up year. Sustained opioid use was not associated with frequent ED use in the multivariable model (OR: 1.06, 95% CI 0.94 to 1.19). Novel associated covariables were benzodiazepine prescription (OR: 1.21, 95% CI 1.12 to 1.30) and polypharmacy (OR: 1.23, 95% CI 1.13 to 1.34). CONCLUSIONS: Due to confounding by social and medical vulnerability, patients with CNCP with sustained opioid use appear to have a higher propensity for frequent ED use in unadjusted models. However, sustained opioid use was not associated with frequent ED use in these patients after adjustment.

Myth and Truth in Opioid Consumption with Intrathecal Morphine Pump Implantation in Chronic Pain: A Retrospective Cohort Study with Claims Database in South Korea.

OBJECTIVE: To investigate the opioid consumption and the healthcare resource utilization in patients with the intrathecal drug delivery system (IDDS) therapy and the comprehensive medical management (CMM) alone. DESIGN: A retrospective cohort study with a customized claims database. SETTING: In a university-based hospital. SUBJECTS: Patients with complex regional pain syndrome, post-laminectomy syndrome, and fibromyalgia. METHODS: Using propensity score matching (1:3), we selected patients with morphine infusion through IDDS (IDDS group) and CMM alone (CMM group). The primary endpoints were comparisons of average morphine equivalents daily dosages (MEDD, mg/day) for 6 and 12 months from an index date. The number of emergency room (ER) visits and hospitalizations and the total medical expenditures were compared as secondary outcomes. RESULTS: In total, 82 patients (N = 23 in the IDDS group and N = 59 in the CMM group) were analyzed. Although a 6-month average MEDD did not reach statistical significance, a 12-month average MEDD was significantly decreased in the IDDS group compared to the CMM group (53.2 ± 46.3 vs 123.9 ± 176.4, respectively; P = 0.008). ER visits were more frequent in the IDDS group than the CMM group at baseline (5.4 vs 0.5, respectively; P = .002), which was maintained for 12 months (P < 0.001). Otherwise, the number of hospitalization and the medical expenditures for pain management were not different between the groups for 12 months. CONCLUSIONS: The combined IDDS therapy had some benefits in reducing opioid consumption for 1-year follow-up compared to the CMM alone in chronic noncancer pain patients.

CDC Clinical Practice Guideline for Prescribing Opioids for Pain - United States, 2022.

This guideline provides recommendations for clinicians providing pain care, including those prescribing opioids, for outpatients aged ≥18 years. It updates the CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016 (MMWR Recomm Rep 2016;65[No. RR-1]:1-49) and includes recommendations for managing acute (duration of <1 month), subacute (duration of 1-3 months), and chronic (duration of >3 months) pain. The recommendations do not apply to pain related to sickle cell disease or cancer or to patients receiving palliative or end-of-life care. The guideline addresses the following four areas: 1) determining whether or not to initiate opioids for pain, 2) selecting opioids and determining opioid dosages, 3) deciding duration of initial opioid prescription and conducting follow-up, and 4) assessing risk and addressing potential harms of opioid use. CDC developed the guideline using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Recommendations are based on systematic reviews of the scientific evidence and reflect considerations of benefits and harms, patient and clinician values and preferences, and resource allocation. CDC obtained input from the Board of Scientific Counselors of the National Center for Injury Prevention and Control (a federally chartered advisory committee), the public, and peer reviewers. CDC recommends that persons with pain receive appropriate pain treatment, with careful consideration of the benefits and risks of all treatment options in the context of the patient's circumstances. Recommendations should not be applied as inflexible standards of care across patient populations. This clinical practice guideline is intended to improve communication between clinicians and patients about the benefits and risks of pain treatments, including opioid therapy; improve the effectiveness and safety of pain treatment; mitigate pain; improve function and quality of life for patients with pain; and reduce risks associated with opioid pain therapy, including opioid use disorder, overdose, and death.

An Observational Study on the Use of a Patient Navigator to Help Improve Outcomes in Patients on Chronic Opioids.

BACKGROUND: In the United States, the prevalence of opioid use disorders has increased in recent years along with an attendant rise in the incidence of chronic pain disorders and prescription opioid use. Patient navigation services have been used to improve health outcomes in cancer and other chronic disease states, but it is unclear whether the implementation of patient navigation services can facilitate improved outcomes among patients receiving chronic opioid therapy. OBJECTIVES: The objective of this study was to compare the outcomes of patients receiving chronic opioid therapy plus patient navigation services and those receiving chronic opioid therapy as a part of usual care. STUDY DESIGN: This was a prospective, observational study. Consecutive patients receiving chronic opioid therapy were enrolled, with alternating assignments to patient navigation (n = 30) or usual care (n = 30). Participants in the patient navigation group received support from a non-physician, non-advanced practice provider staff member who initiated frequent contact via telephone, telemedicine, or in-clinic visits to discuss the patient's health goals. The minimum follow-up period was 90 days. Outcomes qualitatively compared across groups included final pain score, final morphine milligram equivalent (MME) per day, and discharge rates. Risk factors for discharge within the navigation group were assessed. Patient feedback was also solicited. SETTING: This study was conducted at a single independent pain clinic in the United States. RESULTS: Demographic features were similar between the navigator group and the control group. The control group had a higher average initial pain score (7.0/10) than the intervention group (5.9/10) and were receiving a higher initial dose of opioids (23.1 vs 19.0 MME/d). After an average follow-up of 108.7 days, patients in the navigator group had a 16% decrease in final opioid dose compared with a 23% increase in the control group. Furthermore, patients in the control group were discharged from the practice at a higher rate (23.3% vs 6.6%), suggesting increased opioid misuse in the control group compared with the navigator group. In the navigator group, higher levels of anxiety and depression were the primary predictors of discharge. LIMITATIONS: This was a single-center study with a small sample size. The generalizability of these results to other clinic settings is unknown. CONCLUSIONS: Patient navigation decreased opioid use and practice discharge compared with usual care in an independent pain clinic, suggesting a role for patient navigation in reducing opioid misuse and potentially reducing adverse events.

Oxycodone/naloxone versus tapentadol in real-world chronic non-cancer pain management: an observational and pharmacogenetic study.

Tapentadol (TAP) and oxycodone/naloxone (OXN) potentially offer an improved opioid tolerability. However, real-world studies in chronic non-cancer pain (CNCP) remain scarce. Our aim was to compare effectiveness and security in daily pain practice, together with the influence of pharmacogenetic markers. An observational study was developed with ambulatory test cases under TAP (n = 194) or OXN (n = 175) prescription with controls (prescribed with other opioids (control), n = 216) CNCP patients. Pain intensity and relief, quality of life, morphine equivalent daily doses (MEDD), concomitant analgesic drugs, adverse events (AEs), hospital frequentation and genetic variants of OPRM1 (rs1799971, A118G) and COMT (rs4680, G472A) genes, were analysed. Test CNCP cases evidenced a significantly higher pain relief predictable due to pain intensity and quality of life (R2 = 0.3), in front of controls. Here, OXN achieved the greatest pain relief under a 28% higher MEDD, 8-13% higher use of pregabalin and duloxetine, and 23% more prescription change due to pain, compared to TAP. Whilst, TAP yielded a better tolerability due the lower number of 4 [0-6] AEs/patient, in front of OXN. Furthermore, OXN COMT-AA homozygotes evidenced higher rates of erythema and vomiting, especially in females. CNCP real-world patients achieved higher pain relief than other traditional opioids with a better tolerability for TAP. Further research is necessary to clarify the potential influence of COMT and sex on OXN side-effects.

Medical Cannabis Used as an Alternative Treatment for Chronic Pain Demonstrates Reduction in Chronic Opioid Use - A Prospective Study.

BACKGROUND: Chronic opioid therapy (COT) has been used to treat many chronic pain conditions even with poor evidence for its long-term effectiveness. Medical cannabis has emerged with certain pain-relieving properties, which has led to questions as to its' potential application, especially in relation to its effect on opioid use. OBJECTIVES: This study investigates a proposed clinical context in offering medical cannabis as a treatment for chronic pain for those already using chronic opioid therapy. It then details patients' daily morphine milligram equivalent (MME) usage. STUDY DESIGN: This single-center prospective study follows a group of patients trialing medical cannabis treatment for chronic pain that is already using COT in order to determine individual efficacy. Continued medical cannabis treatment was a decision made by the patient, after trialing medical cannabis, to either continue medical cannabis along with COT at a reduced daily MME, or to revert back to their previous COT regimen. SETTING: This study was performed at the Allegheny Health Network Institute for Pain Medicine in Pittsburgh, Pennsylvania. The state of Pennsylvania legalized medical cannabis in April of 2016, and it became available to patients in February of 2018 through medical dispensaries. METHODS: One hundred and fifteen patients met the inclusion criteria, with the majority of those excluded due to not being treated with COT. Of the 115 who chose to undergo a medical cannabis trial in addition to their COT, 75 chose to remain certified for medical cannabis as they had significant pain relief and subsequently weaned down on opioids. Additionally, of the 115 choosing to undergo a medical cannabis trial, 30 chose to be decertified due to ineffectiveness or side effects, and those were placed back on their COT regimen. The other 10 were not included for other denoted reasons. Compliance was monitored through urine drug screens (UDS). RESULTS: There was a 67.1% average decrease in daily MME/patient from 49.9 to 16.4 MME at the first follow-up. There was a 73.3% decrease in MME at second follow-up from 49.9 to 13.3 MME with an ANOVA analysis denoting a significant difference of P < 0.0001. LIMITATIONS: The period of follow-up presented at this point includes their first 6 months of treatment with medical cannabis and COT concomitantly. CONCLUSIONS: Presenting medical cannabis to chronic pain patients on COT should be done in the context of a patient choice between medical cannabis WITH decrement of COT or continued current dose of COT in order to maximize effectiveness in opioid reduction as well as to limit polypharmacy concerns regarding medical cannabis. Allowing for a temporary short-term period where patients may trial medical cannabis, while concomitantly gradually weaning their COT, is also essential in determining medical cannabis' individual effectiveness for that patient's specific type of chronic pain, which should serve to maximize long-term opioid reduction results and hence decrease opioid-related overdose deaths.

Therapeutic alliance impact on analgesic outcomes in a real-world clinical setting: An observational study.

A good therapeutic alliance is relevant for healthcare providers exposed to patients' suffering, especially since patients and physicians may understand the painful experience differently. Our aim was to explore the impact of therapeutic alliance on analgesic outcomes in a real-world interdisciplinary pain unit (PU). A cross-sectional observational study was conducted on outpatients (n = 69) using opioids on a long-term basis for the treatment of chronic non-cancer pain, where clinical pharmacologists and pharmacists advised patients about their opioid treatment. Responses to the patient-doctor relationship questionnaire (PDRQ), sociodemographic and clinical information (pain level, quality of life and hospital use) were collected, whereas pharmacology data (analgesic prescription, adverse events, and compliance) were obtained from electronic health records. Patients were predominantly middle-aged (75 % women, 72 % retired), experiencing moderate pain (VAS 40-70 mm) on average, and under a high morphine equianalgesic dosage (95 ± 88 mg per day, mainly tapentadol or fentanyl). Patients with better PDRQ outcomes, and therefore better therapeutic alliance, showed lower pain intensity than patients with worse PDRQ outcomes (pain intensity: high scores 60 ± 47 mm and medium scores 60 ± 45 mm vs. low scores 80 ± 75 mm, p < 0.01). Along with this, pain intensity was lower when patients affirmed that, thanks to the health-care providers, they "gained new insight", "felt better", or "felt content with their doctor's treatment". What´s more, patients who affirmed "I benefit from the treatment" experienced increased pain relief (benefit 40 ± 30 vs. non-benefit 19 ± 26 mm, p = 0.010) and improved quality of life (benefit 33 ± 25 vs. non-benefit 18 ± 16 mm, p = 0.031). However, there was a percentage of patients who did not fully understand the provided information, which is something to be taken into account to improve in clinical routine. Therapeutic alliance supported by pharmacist experts on pain management can be an effective strategy to improve analgesic outcomes. Further efforts are needed to improve communication strategies for pain management. Future directions of research should include the analysis of the role of the pharmacist in poly-professional consultations as related to the advice of patients about their medication, and the mutual trust with the patients.

Survey of Patients Employing Cannabigerol-Predominant Cannabis Preparations: Perceived Medical Effects, Adverse Events, and Withdrawal Symptoms.

Introduction: Cannabigerol (CBG), and its precursor before decarboxylation, cannabigerolic acid is sometimes labeled the "mother of all cannabinoids." The purpose of the present study was to investigate reasons for use and self-reported therapeutic effects in CBG-predominant cannabis users. Usage patterns and adverse effects, including withdrawal symptoms were also explored. Methods: Cannabidiol-predominant cannabis users were recruited online to complete an online survey assessing CBG use patterns, conditions treated with CBG-predominant cannabis (containing >50% CBG), perceived efficacy, associated adverse events, and withdrawal symptoms. One hundred twenty-seven eligible participants (U.S. residents ages 21+ who reported using CBG-predominant cannabis in the past 6 months) completed the survey. Results: Most of the samples (n=65; 51.2%) reported use of CBG-predominant products solely for medical purposes (n=46; 36.2% reported use for medical and recreational purposes; n=8; 6.3% reported recreational use only, and n=8 were missing). The most common conditions the complete sample reported using CBG to treat were anxiety (51.2%), chronic pain (40.9%), depression (33.1%), and insomnia/disturbed sleep (30.7%). Efficacy was highly rated, with the majority reporting their conditions were "very much improved" or "much improved" by CBG. Furthermore, 73.9% claimed superiority of CBG-predominant cannabis over conventional medicines for chronic pain, 80% for depression, 73% for insomnia, and 78.3% for anxiety. Forty-four percent of CBG-predominant cannabis users reported no adverse events, with 16.5% noting dry mouth, 15% sleepiness, 11.8% increased appetite, and 8.7% dry eyes. Around 84.3% reported no withdrawal symptoms, with sleep difficulties representing the most frequently endorsed withdrawal symptom (endorsed by two respondents). Conclusions: This is the first patient survey of CBG-predominant cannabis use to date, and the first to document self-reported efficacy of CBG-predominant products, particularly for anxiety, chronic pain, depression, and insomnia. Most respondents reported greater efficacy of CBG-predominant cannabis over conventional pharmacotherapy, with a benign adverse event profile and negligible withdrawal symptoms. This study establishes that humans are employing CBG and suggests that CBG-predominant cannabis-based medicines should be studied in randomized controlled trials.

Opioids for chronic pain management in patients with dialysis-dependent kidney failure.

Chronic pain is highly prevalent among adults treated with maintenance haemodialysis (HD) and has profound negative effects. Over four decades, research has demonstrated that 50-80% of adult patients treated with HD report having pain. Half of patients with HD-dependent kidney failure (HDKF) have chronic moderate-to-severe pain, which is similar to the burden of pain in patients with cancer. However, pain management in patients with HDKF is often ineffective as most patients report that their pain is inadequately treated. Opioid analgesics are prescribed more frequently for patients receiving HD than for individuals in the general population with chronic pain, and are associated with increased morbidity, mortality and health-care resource use. Furthermore, current opioid prescribing patterns are frequently inconsistent with guideline-recommended care. Evidence for the effectiveness of opioids in pain management in general, and in patients with HDKF specifically, is lacking. Nonetheless, long-term opioid therapy has a role in the treatment of some patients when used selectively, carefully and combined with an ongoing assessment of risks and benefits. Here, we provide a comprehensive overview of the use of opioid therapy in patients with HDKF and chronic pain, including a discussion of buprenorphine, which has potential as an analgesic option for patients receiving HD owing to its unique pharmacological properties.