- Pharmacological Interventions for Opioid-Induced Hyperalgesia: A Scoping Review of Preclinical Trials. [Review]
- CONCLUSIONS: This scoping review identified plenty of preclinical trials investigating pharmacological interventions for OIH. Using the current literature, it is not possible to directly compare the effectiveness of the interventions. Hence, to identify the most effective interventions for each opioid, the interventions must be indirectly compared in a meta-analysis.
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- Postoperative opioid prescription and patient-reported outcomes after elective spine surgery: a Michigan Spine Surgery Improvement Collaborative study. [Journal Article]J Neurosurg Spine. 2022 Oct 07 [Online ahead of print]JN
- CONCLUSIONS: The opioid epidemic is a serious threat to national public health, and spine surgeons must practice conscientious postoperative opioid prescribing to achieve adequate pain control. The authors' analysis illustrates that a postoperative opioid prescription of 225 MME or less is associated with improved patient satisfaction, greater improvement in physical function, and decreased opioid dependence compared with those who had > 225 MME prescribed.
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- Effects of Daily Methocinnamox Treatment on Fentanyl Self-Administration in Rhesus Monkeys. [Journal Article]
- Methocinnamox (MCAM), a long-acting μ-opioid receptor antagonist, attenuates the positive reinforcing effects of opioids, such as heroin and fentanyl, suggesting it could be an effective treatment of opioid use disorder (OUD). Because treatment of OUD often involves repeated administration of a medication, this study evaluated effects of daily injections of a relatively small dose of MCAM on fent…
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- Characterization of the Discriminative Stimulus Effects of Binary Mixtures of Mu Opioid Receptor Agonists in Rats Discriminating Fentanyl. [Journal Article]J Pharmacol Exp Ther. 2022 03; 380(3):171-179.JP
- Drug overdose deaths involving synthetic opioids, primarily fentanyl, have risen dramatically over the past decade and are currently the driving force of the opioid epidemic in the United States. Fentanyl analogs with greater potency than fentanyl (e.g., carfentanil) pose serious risk to public health. Although fentanyl analogs are primarily encountered by humans as constituents of a mixture of d…
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- Methadone, Buprenorphine, Oxycodone, Fentanyl and Tramadol in Multiple Postmortem Matrices. [Journal Article]
- Peripheral blood (PB) concentrations are generally preferred for postmortem toxicological interpretation, but some autopsy cases may lack blood for sampling due to decomposition or large traumas, etc. In such cases, other tissues or bodily fluids must be sampled; however, limited information exists on postmortem concentrations in matrices other than blood. Pericardial fluid (PF), muscle and vitre…
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- A Multicriteria Decision Analysis Comparing Pharmacotherapy for Chronic Neuropathic Pain, Including Cannabinoids and Cannabis-Based Medical Products. [Journal Article]
- Background: Pharmacological management of chronic neuropathic pain (CNP) still represents a major clinical challenge. Collective harnessing of both the scientific evidence base and clinical experience (of clinicians and patients) can play a key role in informing treatment pathways and contribute to the debate on specific treatments (e.g., cannabinoids). A group of expert clinicians (pain speciali…
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- Preoperative Fluoroscopically Guided Regional Erector Spinae Plane Blocks Reduce Opioid Use, Increase Mobilization, and Reduce Length of Stay Following Lumbar Spine Fusion. [Journal Article]
- CONCLUSIONS: ESP blocks significantly reduced postop opioid use following lumbar fusion. Block patients ambulated further with PT, had reduced length of stay, and had improved PROMIS PI postoperatively. Validation of the block demonstrated the effectiveness of a novel fluoroscopic delivery technique. ESP blocks represent an underutilized method of reducing opioid consumption, improving postoperative mobilization and reducing length of stay following lumbar spine fusion.
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- Methocinnamox Reverses and Prevents Fentanyl-Induced Ventilatory Depression in Rats. [Journal Article]
- Opioid use disorder affects over 2 million Americans with an increasing number of deaths due to overdose from the synthetic opioid fentanyl and its analogs. The Food and Drug Administration-approved opioid receptor antagonist naloxone (e.g., Narcan) is used currently to treat overdose; however, a short duration of action limits its clinical utility. Methocinnamox (MCAM) is a long-lasting opioid r…
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- The Balanced Opioid Initiative: protocol for a clustered, sequential, multiple-assignment randomized trial to construct an adaptive implementation strategy to improve guideline-concordant opioid prescribing in primary care. [Randomized Controlled Trial]
- Rates of opioid prescribing tripled in the USA between 1999 and 2015 and were associated with significant increases in opioid misuse and overdose death. Roughly half of all opioids are prescribed in primary care. Although clinical guidelines describe recommended opioid prescribing practices, implementing these guidelines in a way that balances safety and effectiveness vs. risk remains a challenge…
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- Demographic and Perioperative Factors Associated With Patient-reported Outcomes Measurement Information System (PROMIS) Survey Completion. [Journal Article]
- CONCLUSIONS: This study identified demographic and perioperative variables associated with PROMIS survey completion and response rates. Patients who underwent surgery in the outpatient setting and those with high preoperative radicular limb pain were less likely to complete surveys. Interestingly, patients with clinical signs of depression were more likely to fill out surveys. Understanding variables associated with survey completion may provide the clinician with insight into which demographic groups are the most at-risk for not responding to surveys.
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- OREX-1019: A Novel Treatment of Opioid Use Disorder and Relapse Prevention. [Journal Article]
- There is an urgent need for new pharmacological treatments for substance use disorders, including opioid use disorder, particularly for use in relapse prevention. A combination of buprenorphine with naltrexone has shown particular promise, with clinical studies indicating a substantial improvement over treatment with naltrexone alone. OREX-1019 (formerly BU10119) is a compound that mimics the pha…
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- Methocinnamox Produces Long-Lasting Antagonism of the Behavioral Effects of µ-Opioid Receptor Agonists but Not Prolonged Precipitated Withdrawal in Rats. [Journal Article]
- A novel µ-opioid receptor antagonist, methocinnamox (MCAM), attenuates some abuse-related and toxic effects of opioids. This study further characterized the pharmacology of MCAM in separate groups of rats using procedures to examine antinociception, gastrointestinal motility, and withdrawal in morphine-dependent rats. Antinociceptive effects of opioid receptor agonists were measured before and af…
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- PROMIS Physical Function for prediction of postoperative pain, narcotics consumption, and patient-reported outcomes following minimally invasive transforaminal lumbar interbody fusion. [Journal Article]
- OBJECTIVEThis study aimed to determine if the preoperative Patient-Reported Outcomes Measurement Information System, Physical Function (PROMIS PF) score is predictive of immediate postoperative patient pain and narcotics consumption or long-term patient-reported outcomes (PROs) following minimally invasive transforaminal lumbar interbody fusion (MIS TLIF).METHODSA prospectively maintained databas…
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- Reversal and Prevention of the Respiratory-Depressant Effects of Heroin by the Novel μ-Opioid Receptor Antagonist Methocinnamox in Rhesus Monkeys. [Journal Article]
- One consequence of the ongoing opioid epidemic is a large number of overdose deaths. Naloxone reverses opioid-induced respiratory depression; however, its short duration of action limits the protection it can provide. Methocinnamox (MCAM) is a novel opioid receptor antagonist with a long duration of action. This study examined the ability of MCAM to prevent and reverse the respiratory-depressant …
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- Long-Lasting Effects of Methocinnamox on Opioid Self-Administration in Rhesus Monkeys. [Journal Article]
- Opioid abuse remains a serious public health challenge, despite the availability of medications that are effective in some patients (naltrexone, buprenorphine, and methadone). This study explored the potential of a pseudoirreversible mu-opioid receptor antagonist [methocinnamox (MCAM)] as a treatment for opioid abuse by examining its capacity to attenuate the reinforcing effects of mu-opioid rece…
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- Impact of capillary flow hydrodynamics on carrier-mediated transport of opioid derivatives at the blood-brain barrier, based on pH-dependent Michaelis-Menten and Crone-Renkin analyses. [Journal Article]
- Most studies of blood-brain barrier (BBB) permeability and transport are conducted at a single pH, but more detailed information can be revealed by using multiple pH values. A pH-dependent biophysical model was applied to the mechanistic analysis of published pH-dependent BBB luminal uptake data from three opioid derivatives in rat: pentazocine (Suzuki et al., 2002a, 2002b), naloxone (Suzuki et a…
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- Increases in Fentanyl-Related Overdose Deaths - Florida and Ohio, 2013-2015. [Journal Article]
- In March and October 2015, the Drug Enforcement Administration (DEA) and CDC issued nationwide alerts identifying fentanyl, particularly illicitly manufactured fentanyl (IMF), as a threat to public health and safety (1,2). IMF is pharmacologically similar to pharmaceutical fentanyl (PF), but is unlawfully produced in clandestine laboratories, obtained via illicit drug markets, and includes fentan…
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- New Morphine Analogs Produce Peripheral Antinociception within a Certain Dose Range of Their Systemic Administration. [Journal Article]
- Growing data support peripheral opioid antinociceptive effects, particularly in inflammatory pain models. Here, we examined the antinociceptive effects of subcutaneously administered, recently synthesized 14-O-methylmorphine-6-O-sulfate (14-O-MeM6SU) compared with morphine-6-O-sulfate (M6SU) in a rat model of inflammatory pain induced by an injection of complete Freund's adjuvant and in a mouse m…
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- Combined Treatment with Morphine and Δ9-Tetrahydrocannabinol in Rhesus Monkeys: Antinociceptive Tolerance and Withdrawal. [Journal Article]
- Opioid receptor agonists are effective for treating pain; however, tolerance and dependence can develop with repeated use. Combining opioids with cannabinoids can enhance their analgesic potency, although it is less clear whether combined treatment alters opioid tolerance and dependence. In this study, four monkeys received 3.2 mg/kg morphine alone or in combination with 1 mg/kg Δ(9)-tetrahydroca…
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- Intrathecal administration of nociceptin/orphanin FQ receptor agonists in rats: A strategy to relieve chemotherapy-induced neuropathic hypersensitivity. [Journal Article]
- Oxaliplatin and paclitaxel are considered central components in the treatment of colorectal and breast cancer, respectively. The development of neuropathy during chronic treatment represents the major dose-limiting side effect that leads to discontinuation or interruption of therapies. The management of neuropathy is a challenge to individuate innovative therapeutic strategies based on new target…
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- Deficits in spontaneous burrowing behavior in the rat bilateral monosodium iodoacetate model of osteoarthritis: an objective measure of pain-related behavior and analgesic efficacy. [Journal Article]
- CONCLUSIONS: Burrowing behavior provides an objective, non-reflexive read-out for pain-related behavior in the MIA model that has predictive validity in detecting analgesic efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) and an anti-NGF mAb.
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- Acute and subchronic antinociceptive effects of nociceptin/orphanin FQ receptor agonists infused by intrathecal route in rats. [Journal Article]
- Severe pain occurs in the context of many diseases and conditions and is a leading cause of disability. Nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand of the N/OFQ peptide (NOP) receptor. This peptidergic system controls pain transmission and in particular spinally administered N/OFQ has robust antinociceptive properties. The aim of this study was to investigate the spinal antinociceptiv…
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- Differential effects of endocannabinoid catabolic inhibitors on morphine withdrawal in mice. [Journal Article]
- CONCLUSIONS: These findings suggest that inhibiting endocannabinoid catabolic enzymes reduces somatic morphine withdrawal signs, but not aversive aspects as inferred in the CPA paradigm. The observation that non-dependent mice administered inhibitors of endocannabinoid degradation did not display place preferences is consistent with the idea that that endocannabinoid catabolic enzymes might be targeted therapeutically, with reduced risk of abuse.
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- Comparison of epidural versus intrathecal anaesthesia in dogs undergoing pelvic limb orthopaedic surgery. [Randomized Controlled Trial]
- CONCLUSIONS: HIA was found to have lower PF, lower intraoperative analgesic failure and faster motor block resolution. In this study HIA was shown to provide some advantages over EA in dogs undergoing commonly performed pelvic limb orthopaedic surgery in a day-hospital regime.
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- Impact of efficacy at the μ-opioid receptor on antinociceptive effects of combinations of μ-opioid receptor agonists and cannabinoid receptor agonists. [Journal Article]
- Cannabinoid receptor agonists, such as Δ(9)-tetrahydrocannabinol (Δ(9)-THC), enhance the antinociceptive effects of μ-opioid receptor agonists, which suggests that combining cannabinoids with opioids would improve pain treatment. Combinations with lower efficacy agonists might be preferred and could avoid adverse effects associated with large doses; however, it is unclear whether interactions bet…
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- Inhibition of TRPM8 channels reduces pain in the cold pressor test in humans. [Randomized Controlled Trial]
- The transient receptor potential (subfamily M, member 8; TRPM8) is a nonselective cation channel localized in primary sensory neurons, and is a candidate for cold thermosensing, mediation of cold pain, and bladder overactivity. Studies with TRPM8 knockout mice and selective TRPM8 channel blockers demonstrate a lack of cold sensitivity and reduced cold pain in various rodent models. Furthermore, T…
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- CB1 antagonism: interference with affective properties of acute naloxone-precipitated morphine withdrawal in rats. [Journal Article]
- CONCLUSIONS: Neutral antagonism of the CB1 receptor reduces the aversive affective properties of morphine withdrawal.
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- Dual inhibition of endocannabinoid catabolic enzymes produces enhanced antiwithdrawal effects in morphine-dependent mice. [Journal Article]
- Inhibition of the endocannabinoid catabolic enzymes, monoacylglycerol lipase (MAGL) or fatty acid amide hydrolase (FAAH) attenuates naloxone-precipitated opioid withdrawal signs in mice via activation of CB1 receptors. Complete FAAH inhibition blocks only a subset of withdrawal signs, whereas complete MAGL inhibition elicits enhanced antiwithdrawal efficacy, but is accompanied with some cannabimi…
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- Opioid-induced hypernociception is associated with hyperexcitability and altered tetrodotoxin-resistant Na+ channel function of dorsal root ganglia. [Journal Article]
- Opiates are potent analgesics for moderate to severe pain. Paradoxically, patients under chronic opiates have reported hypernociception, the mechanisms of which are unknown. Using standard patch-clamp technique, we examined the excitability, biophysical properties of tetrodotoxin-resistant (TTX-R) Na(+) and transient receptor potential vanilloid 1 (TRPV1) channels of dorsal root ganglia neurons (…
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- Design and discovery of a selective small molecule κ opioid antagonist (2-methyl-N-((2'-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine, PF-4455242). [Journal Article]
- By use of parallel chemistry coupled with physicochemical property design, a series of selective κ opioid antagonists have been discovered. The parallel chemistry strategy utilized key monomer building blocks to rapidly expand the desired SAR space. The potency and selectivity of the in vitro κ antagonism were confirmed in the tail-flick analgesia model. This model was used to build an exposure-r…
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