scholarly journals Mice with High FGF21 Serum Levels Had a Reduced Preference for Morphine and an Attenuated Development of Acute Antinociceptive Tolerance and Physical Dependence

2021 ◽  
Author(s):  
Louben Dorval ◽  
Brian I. Knapp ◽  
Olufolake A. Majekodunmi ◽  
Sophia Eliseeva ◽  
Jean M Bidlack
Keyword(s):  
Pain Treatment ◽  
Therapeutic Potential ◽  
Physical Dependence ◽  
Serum Levels ◽  
Opioid Use Disorder ◽  
Fibroblast Growth Factor 21 ◽  
Opioid Use ◽  
Chronic Morphine ◽  
Hot Plate ◽  
Antinociceptive Tolerance

As a result of the opioid epidemic, there is a desire to identify new targets for treating opioid use disorder. Previous studies showed that fibroblast growth factor 21 (FGF21) decreased alcohol and sweet preference in mice. In this study, FGF21-transgenic (FGF21-Tg) mice, expressing high FGF21 serum levels, and wildtype (WT) C57BL/6J littermates were treated with morphine and saline to determine if differences exist in their physiological and behavioral responses to opioids. FGF21-Tg mice displayed reduced preference for morphine in the conditioned place preference assay compared to WT littermates. Similarly, FGF21-Tg mice had an attenuation of the magnitude and rate of acute morphine antinociceptive tolerance development, and acute and chronic morphine physical dependence, but exhibited no change in chronic morphine antinociceptive tolerance. The ED50 values for morphine-induced antinociception in the 55-degree C hot plate and the 55-degree C warm-water tail withdrawal assays were similar in both strains of mice. Likewise, FGF21-Tg and WT littermates had comparable responses to morphine-induced respiratory depression. Overall, FGF21-Tg mice had an attenuated preference for morphine, a reduced development of morphine-induced dependence, and a reduction in the development of acute morphine antinociceptive tolerance. FGF21 and its receptor have therapeutic potential for reducing opioid withdrawal symptoms and craving, and augmenting opioid therapeutics for acute pain treatment.

Abuse of Opioids and Prescription Medications

2016 ◽  
Author(s):  
Isis Burgos-Chapman ◽  
Louis A. Trevisan ◽  
Kevin Sevarino
Keyword(s):  
Pain Treatment ◽  
The Elderly ◽  
Pain Medication ◽  
Opioid Use Disorder ◽  
Prescription Medications ◽  
Opioid Use ◽  
Opioid Medication ◽  
Medication Misuse ◽  
Chronic Pain Treatment

This chapter reviews an under-recognized aspect of geriatrics. The elderly population is growing in number, as is the proportion of aging baby-boomers at high risk for pain medication misuse and opioid use disorders. Given the widespread use of opioids in pain management, one can expect that problems with opioid use will increase among the elderly in the coming years. We describe the magnitude of the problem and discuss the importance of risk-stratification to identify which older patients are at elevated risk to develop problems with opioids. We examine the role of opioids in chronic pain treatment and the pitfalls of their use in the elderly. Finally, we provide general guidelines for the treatment of pain medication misuse and/or an opioid use disorder in the elderly. Opioid medication misuse and use disorders should be on every practitioner’s radar as a possible reason for problems surfacing in the elderly patient.

Identification of a Novel Spinal Dorsal Horn Astroglial d-Amino Acid Oxidase–Hydrogen Peroxide Pathway Involved in Morphine Antinociceptive Tolerance

2014 ◽  
Vol 120 (4) ◽  
pp. 962-975 ◽  
Author(s):  
Nian Gong ◽  
Xin-Yan Li ◽  
Qi Xiao ◽  
Yong-Xiang Wang
Keyword(s):  
Hydrogen Peroxide ◽  
Morphine Tolerance ◽  
Acid Oxidase ◽  
Oxygen Species ◽  
Morphine Treatment ◽  
Amino Acid Oxidase ◽  
Chronic Morphine ◽  
Hot Plate ◽  
Antinociceptive Tolerance ◽  
Interfering Rna

Abstract Background: d-Amino acid oxidase (DAAO) is a flavin adenine dinucleotide-dependent peroxisomal flavoenzyme which is almost exclusively expressed within astrocytes in the spinal cord. DAAO catalyzes oxidation of d-amino acids to hydrogen peroxide, which is a stable and less active reactive oxygen species, and may represent a final form of reactive oxygen species. This study tested the hypothesis that the spinal astroglial DAAO–hydrogen peroxide pathway plays an important role in the development of morphine antinociceptive tolerance. Methods: Rat and mouse formalin, hot-plate, and tail-flick tests were used, and spinal DAAO expression and hydrogen peroxide level were measured. Sample size of animals was six in each study group. Results: Subcutaneous and intrathecal DAAO inhibitors, including 5-chloro-benzo[d]isoxazol-3-ol, AS057278, and sodium benzoate, completely prevented and reversed morphine antinociceptive tolerance in the formalin, hot-plate, and tail-immersion tests, with a positive correlation to their DAAO inhibitory activities. Intrathecal gene silencers, small interfering RNA/DAAO and small hairpin RNA/DAAO, almost completely prevented morphine tolerance. Intrathecal 5-chloro-benzo[d]isoxazol-3-ol and small interfering RNA/DAAO completely prevented increased spinal hydrogen peroxide levels after chronic morphine treatment. Intrathecal nonselective hydrogen peroxide scavenger phenyl-tert-N-butyl nitrone and the specific hydrogen peroxide catalyst catalase also abolished established morphine tolerance. Spinal dorsal horn astrocytes specifically expressed DAAO was significantly up-regulated, accompanying astrocyte hypertrophy after chronic morphine treatment. Conclusions: For the first time, the authors’ result identify a novel spinal astroglial DAAO–hydrogen peroxide pathway that is critically involved in the initiation and maintenance of morphine antinociceptive tolerance, and suggest that this pathway is of potential utility for the management of morphine tolerance and chronic pain.

scholarly journals The dual orexin/hypocretin receptor antagonist suvorexant reduces addiction-like behaviors for the opioid fentanyl

2020 ◽  
Author(s):  
Shayna L. O’Connor ◽  
Jennifer E. Fragale ◽  
Morgan H James ◽  
Gary Aston-Jones
Keyword(s):  
Drugs Of Abuse ◽  
Therapeutic Potential ◽  
Opioid Use Disorder ◽  
Opioid Use ◽  
Self Administration ◽  
Drug Experience ◽  
Reward Seeking ◽  
Intermittent Access ◽  
General Locomotor Activity ◽  
Target Effects

AbstractThe orexin (hypocretin) system is critical for motivated seeking of all drugs of abuse, including opioids. In 2019, the National Institute on Drug Addiction (NIDA) identified the orexin system as a high priority target mechanism for novel pharmacological therapies to treat opioid use disorder (OUD). Suvorexant (Belsomra™) is a dual orexin receptor 1/orexin receptor 2 (OxR1/OxR2) antagonist that is FDA-approved for the treatment of insomnia, and thus has the potential to be readily repurposed for the treatment of OUD. However, studies have yet to test the therapeutic potential of suvorexant with respect to reducing opioid-related behaviors. Accordingly, here we investigated the efficacy of suvorexant in reducing several addiction-relevant behaviors in fentanyl self-administrating rats. In rats with limited drug experience, suvorexant decreased motivation for fentanyl on a behavioral economics (BE) task. This effect was greatest in rats with the highest motivation for fentanyl. Suvorexant was even more effective at decreasing motivation for fentanyl following induction of a more robust addiction phenotype by intermittent access (IntA) self-administration of the opioid. Suvorexant also attenuated punished responding for fentanyl and reduced cued reinstatement in IntA rats. Suvorexant did not affect general locomotor activity or natural reward seeking, indicating that at the doses used here, suvorexant can be used to reduce drug seeking with limited sedative or off-target effects. Together, these results highlight the therapeutic potential of suvorexant, particularly in individuals with the severe OUD.

Non-Opioid Alternatives to Managing Chronic Pain

2019 ◽  
pp. 55-64
Author(s):  
Vanila Singh ◽  
Rachel Katonak
Keyword(s):  
Public Health ◽  
Chronic Pain ◽  
Criminal Behavior ◽  
Pain Treatment ◽  
Well Being ◽  
Evidence Base ◽  
Opioid Use Disorder ◽  
Opioid Use ◽  
Prescription Drug Monitoring Programs ◽  
Pain Patients

While public health practitioners generally focus on the primary prevention of illness and disease by developing programs and policies that promote health and well-being, an understanding of chronic pain and its treatment is important for public health professionals working to address the opioid crisis. There are unintended consequences of well-intentioned policies that may restrict prescribing behavior or otherwise interrupt or change access to opioids. For example, one consequence of expanding state prescription drug monitoring programs has been concern by providers that “legitimate” pain patients may be subjected to increased suspicion and stigma and not able to obtain needed medications. State and federal efforts to shut down “pill mills” are vital to addressing diversion and criminal behavior, but pain patients who are also seen in these clinics may have an interruption in their treatment or access to medication. Understanding chronic pain treatment and non-opioid alternatives to pain management is an important part of developing sound public health policies to prevent opioid use disorder and its sequelae. This chapter presents these alternatives and the evidence base for each.

scholarly journals A Comparison of the Antinociceptive Properties of SJP-005 and Morphine in Rats

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 243
Author(s):  
Joris C Verster ◽  
Andrew Scholey ◽  
Thomas A Dahl ◽  
Jacqueline M Iversen
Keyword(s):  
Subcutaneous Injection ◽  
Antinociceptive Effect ◽  
Opioid Use Disorder ◽  
Opioid Use ◽  
Hot Plate ◽  
Double Blind ◽  
Hot Plate Test ◽  
Plate Test ◽  
Test Study ◽  
Group 5

SJP-005 (a combination of ketotifen and ibuprofen) is being developed as a potential treatment for pain and for opioid use disorder. It is therefore important to investigate the potential antinociceptive properties of SJP-005. Two studies were conducted to evaluate the potential effects of SJP-005 in rats. Study 1 applied the von Frey test to examine the antinociceptive effect of morphine with and without SJP-005 in adjuvant-induced hypersensitivity to tactile stimulation. In a double-blind, between-groups design, groups of rats (n = 10 each) received morphine at 3, 10, or 30 mg/kg bodyweight (bw) (subcutaneous injection) with or without SJP-005 (oral). Mechanic allodynia and paw volume were assessed before and after treatment. Study 2 utilized the hot plate test. Using a crossover design, groups of rats (n = 10 each) received either morphine at 3, 10, or 30 mg/kg bw (subcutaneous injection) preceded by oral administration of placebo (Week 1) or SJP-005 (Week 2). In Study 1, in the von Frey up-and-down test, Δ paw withdrawal responses in Group 1 (3 mg/kg bw morphine) were significantly lower compared to those in Group 4 (3 mg/kg bw morphine plus SJP-005), whereas the differences in Δ paw withdrawal between Group 2 and Group 5 (10 mg/kg bw morphine with and without SJP-005) and between Group 3 and Group 6 (10 mg/kg bw morphine with and without SJP-005) did not reach statistical difference. Trendline analysis of the dose–response relationship for the morphine + placebo groups and morphine + SJP-005 groups revealed no significant differences in the intercepts and slopes. In Study 2, no significant differences were observed on hot plate performance between morphine and morphine in combination with SJP-005. In conclusion, the findings in the von Frey up-and-down test (Study 1) suggest that animals can withstand higher levels of painful stimuli when SJP-005 is co-administered. This may also suggest a possible opioid sparing effect. However, in the hot plate test (Study 2), animals did not respond more adaptively to stronger painful stimuli after co-administering SJP-005. These observations warrant further investigation of the antinociceptive properties of SJP-005.

Acute Pain Management for Patients Receiving Medication-Assisted Therapy

2019 ◽  
Vol 30 (4) ◽  
pp. 335-342
Author(s):  
Peggy Compton
Keyword(s):  
Pain Management ◽  
Acute Pain ◽  
Pain Treatment ◽  
Management Strategies ◽  
Immediate Release ◽  
Opioid Use Disorder ◽  
Health Issues ◽  
Opioid Use ◽  
Opioid Medications ◽  
Analgesic Opioids

Evidence-based approaches for the treatment of opioid use disorder include the use of opioid medications (methadone, buprenorphine, or naltrexone), collectively referred to as medication-assisted therapy. Patients receiving medication-assisted therapy may present in the acute care setting with pain, often related to planned surgical procedures to treat health issues that were not addressed before entering treatment. Because these medications act on the same receptors as do analgesic opioids—and, in the cases of methadone and buprenorphine, have analgesic properties — managing acute pain in these patients can be challenging. Principles of effective pain management for these patients include continuing the usual medication-assisted therapy dose; using nonpharmacological and nonopioid pain management strategies as possible and immediate-release opioids, titrating to effect and monitoring for toxicity; anticipating tolerance and hyperalgesia; and establishing a collaborative treatment relationship with the medication-assisted therapy provider. Providing effective pain treatment supports ongoing recovery in patients with opioid use disorder.

scholarly journals Treatment of Opioid Use Disorder With Buprenorphine-Naloxone at Chainama Hills College Hospital in Lusaka, Zambia: A Case Report

2020 ◽  
Vol 2 (4) ◽  
Author(s):  
Brian Maila ◽  
Anatolii Tsarkov ◽  
Petro Petlovanyi ◽  
Gaise Kweku ◽  
Evans Musonda
Keyword(s):  
Physical Dependence ◽  
Opioid Use Disorder ◽  
Opioid Use ◽  
College Hospital ◽  
The Central Nervous System ◽  
Chronic Opioid Use ◽  
Opioid Withdrawal Syndrome ◽  
Recreational Use ◽  
Chronic Use

Opioid dependence is a disorder of the central nervous system that results from chronic use of opiates. Opioids cause intense feelings of euphoria, and this is what puts opiate users at risk of recreational use of these substances. There is a desire to increase the dose in order to enhance the effect of opioids, therefore addiction arises, which is a serious medical and social problem. The more opiates come from outside, the less natural opiates are produced, and more opiates are required to create a strong feeling of euphoria, which previously could be achieved with a lower dose. The consequence of a chronic opioid use is the drug tolerance, and abrupt cessation of use causes a serious condition of opioid withdrawal syndrome, indicating the presence of physical dependence. This article describes the experience and the case study of Medication Assisted Therapy (MAT) with buprenorphine and naloxone at Chainama Hills College Hospital in Lusaka, Zambia. 

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