scholarly journals Lack of effect of different pain-related manipulations on opioid self-administration, reinstatement of opioid seeking, and opioid choice in rats

2021 ◽  
Author(s):  
David J Reiner ◽  
E Andrew Townsend ◽  
Javier Orihuel Menendez ◽  
Sarah V Applebey ◽  
Sarah M Claypool ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Pain Relief ◽  
Inflammatory Pain ◽  
Experimental Pain ◽  
Reinforcement Rate ◽  
Opioid Addiction ◽  
Self Administration ◽  
Related Factors ◽  
Behavioral Impairments ◽  
Context Specific

ABSTRACTRationale and ObjectivePain-related factors increase risk for opioid addiction, and opioid-induced pain relief may function as a negative reinforcer to increase opioid taking and seeking. However, experimental pain-related manipulations generally do not increase opioid self-administration in rodents. This discrepancy may reflect insufficient learning of pain-relief contingencies or confounding effects of pain-related behavioral impairments. Here we determined if pairing noxious stimuli with opioid self-administration would promote pain-related reinstatement of opioid seeking or increase opioid choice over food.MethodsIn Experiment 1, rats self-administered fentanyl in the presence or absence of repeated intraplantar capsaicin injections in distinct contexts to model context-specific exposure to cutaneous nociception. After capsaicin-free extinction in both contexts, we tested if capsaicin would reinstate fentanyl seeking. In Experiment 2, rats self-administered heroin after intraperitoneal (i.p.) lactic acid injections to model acute visceral inflammatory pain. After lactic acid-free extinction, we tested if lactic acid would reinstate heroin seeking. In Experiment 3, we tested if repeated i.p. lactic acid or intraplantar Complete Freund’s Adjuvant (CFA; to model sustained inflammatory pain) would increase fentanyl choice over food.ResultsIn Experiments 1-2, neither capsaicin nor lactic acid reinstated opioid seeking after extinction, and lactic acid did not increase heroin-induced reinstatement. In Experiment 3, lactic acid and CFA decreased reinforcement rate without affecting fentanyl choice.ConclusionsResults extend the range of conditions across which pain-related manipulations fail to increase opioid seeking in rats and suggest that enhanced opioid-addiction risk in humans with chronic pain involves factors other than enhanced opioid reinforcement and relapse.

scholarly journals Inflammatory Pain Promotes Increased Opioid Self-Administration: Role of Dysregulated Ventral Tegmental Area   Opioid Receptors

2015 ◽  
Vol 35 (35) ◽  
pp. 12217-12231 ◽  
Author(s):  
L. Hipolito ◽  
A. Wilson-Poe ◽  
Y. Campos-Jurado ◽  
E. Zhong ◽  
J. Gonzalez-Romero ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Opioid Receptors ◽  
Inflammatory Pain ◽  
Self Administration ◽  
Ventral Tegmental

scholarly journals Context-Specific Procedures for the Diagnosis of Human Schistosomiasis – A Mini Review

2021 ◽  
Vol 2 ◽  
Author(s):  
Pytsje T. Hoekstra ◽  
Govert J. van Dam ◽  
Lisette van Lieshout
Keyword(s):  
Diagnostic Tests ◽  
Point Of Care ◽  
Public Health Problem ◽  
Nucleic Acid Amplification ◽  
Antibody Detection ◽  
Infection Model ◽  
Related Factors ◽  
Human Schistosomiasis ◽  
Diagnostic Approaches ◽  
Context Specific

Schistosomiasis is a parasitic disease caused by trematode blood flukes of the genus Schistosoma, affecting over 250 million people mainly in the tropics. Clinically, the disease can present itself with acute symptoms, a stage which is relatively more common in naive travellers originating from non-endemic regions. It can also develop into chronic disease, with the outcome depending on the Schistosoma species involved, the duration and intensity of infection and several host-related factors. A range of diagnostic tests is available to determine Schistosoma infection, including microscopy, antibody detection, antigen detection using the Point-Of-Care Circulating Cathodic Antigen (POC-CCA) test and the Up-Converting Particle Lateral Flow Circulating Anodic Antigen (UCP-LF CAA) test, as well as Nucleic Acid Amplification Tests (NAATs) such as real-time PCR. In this mini review, we discuss these different diagnostic procedures and explore their most appropriate use in context-specific settings. With regard to endemic settings, diagnostic approaches are described based on their suitability for individual diagnosis, monitoring control programs, determining elimination as a public health problem and eventual interruption of transmission. For non-endemic settings, we summarize the most suitable diagnostic approaches for imported cases, either acute or chronic. Additionally, diagnostic options for disease-specific clinical presentations such as genital schistosomiasis and neuro-schistosomiasis are included. Finally, the specific role of diagnostic tests within research settings is described, including a controlled human schistosomiasis infection model and several clinical studies. In conclusion, context-specific settings have different requirements for a diagnostic test, stressing the importance of a well-considered decision of the most suitable diagnostic procedure.

scholarly journals The Role of Propolis in Pulp Pain by Inhibiting Cyclooxygenase-2 Expression

2021 ◽  
Vol 11 (1) ◽  
pp. 11
Author(s):  
Ira Widjiastuti ◽  
Widya Saraswati ◽  
Annisa Rahma
Keyword(s):  
Side Effects ◽  
Pain Relief ◽  
Inflammatory Pain ◽  
Cyclooxygenase 2 ◽  
Propolis Extract ◽  
In Silico Studies ◽  
Cox 2

Background: Inflammation of the pulp can lead to elicit pain. Pain in inflammation is induced by the cyclooxygenase-2 enzyme (COX-2) which induces prostaglandin E2 (PGE2) resulting in pain. Pain in the pulp can be relieved by eugenol. In its application, eugenol is toxic to pulp fibroblasts. Due to the side effect, it is worth considering other biocompatible materials with minimal side effects, such as propolis. Flavonoids and phenolic acids that contained in propolis can inhibit COX-2. Therefore, an analysis outlined in the literature review is needed to examine the results of research related to the role of propolis as pulp pain relief by inhibiting COX-2 expression. Purpose: To analyze the role of propolis in pulp pain by inhibiting COX-2 expression. Reviews: Propolis extract that extracted by ethanol, water, and hydroalcohol has pain relief properties in the pulp by inhibiting COX-2 by directly binding to the COX-2 receptors and by reducing the production of proinflammatory cytokines which are COX-2 inducers, proven through in vivo, in vitro, and in silico studies in various target cell organs. Conclusion: Propolis extract has high prospect as inflammatory pain inhibitor in the pulp by inhibit COX-2 expression.

scholarly journals Fentanyl vapor self-administration model in mice to study opioid addiction

2020 ◽  
Vol 6 (32) ◽  
pp. eabc0413 ◽  
Author(s):  
K. Moussawi ◽  
M. M. Ortiz ◽  
S. C. Gantz ◽  
B. J. Tunstall ◽  
R. C. N. Marchette ◽  
...  
Keyword(s):  
Mouse Model ◽  
Opioid Addiction ◽  
Dopamine Neurons ◽  
Drug Intake ◽  
Self Administration ◽  
Protracted Abstinence ◽  
Electrophysiological Recordings ◽  
Lower Amplitude ◽  
The Many ◽  
Intravenous Catheterization

Intravenous drug self-administration is considered the “gold standard” model to investigate the neurobiology of drug addiction in rodents. However, its use in mice is limited by frequent complications of intravenous catheterization. Given the many advantages of using mice in biomedical research, we developed a noninvasive mouse model of opioid self-administration using vaporized fentanyl. Mice readily self-administered fentanyl vapor, titrated their drug intake, and exhibited addiction-like behaviors, including escalation of drug intake, somatic signs of withdrawal, drug intake despite punishment, and reinstatement of drug seeking. Electrophysiological recordings from ventral tegmental area dopamine neurons showed a lower amplitude of GABAB receptor–dependent currents during protracted abstinence from fentanyl vapor self-administration. This mouse model of fentanyl self-administration recapitulates key features of opioid addiction, overcomes limitations of the intravenous model, and allows investigation of the neurobiology of opioid addiction in unprecedented ways.

scholarly journals Ipsi- and Contralateral Moxibustion Generate Similar Analgesic Effect on Inflammatory Pain

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Chuan-Yi Zuo ◽  
Peng Lv ◽  
Cheng-Shun Zhang ◽  
Ru-Xue Lei ◽  
Wei Zhou ◽  
...  
Keyword(s):  
Pain Relief ◽  
Phase I ◽  
Phase Ii ◽  
Inflammatory Pain ◽  
Analgesic Effect ◽  
Withdrawal Latency ◽  
Significant Difference ◽  
Freund’S Adjuvant ◽  
Freund's Adjuvant ◽  
Biting Time

The aim of this study was to investigate whether contralateral moxibustion would generate a similar analgesic effect with ipsilateral moxibustion. Contra- and ipsilateral moxibustion were separately applied to Zusanli (ST36) acupoints of inflammatory pain mice. The analgesic effect was evaluated, respectively, by licking/biting time (LBT) of formalin-induced inflammatory pain and thermal withdrawal latency (TWL) of complete Freund’s adjuvant- (CFA-) induced inflammatory pain. For formalin-induced pain, compared with formalin group, the total LBT of ipsi- and contralateral moxibustion reduced in both phase I and phase II, but there was no significant difference between ipsi- and contralateral moxibustion. For CFA-induced inflammatory pain, compared with CFA group, TWL of ipsi- and contra-Moxi groups increased immediately after moxibustion intervention; however there was no obvious difference between ipsi- and contralateral moxibustion at any timepoint. It indicated that contralateral moxibustion had a similar analgesic effect with ipsilateral moxibustion in both formalin- and CFA-induced pain. These results suggest that both ipsi- and contralateral moxibustion could be applied for pain relief.

scholarly journals Higher anhedonia during withdrawal from initial opioid exposure is protective against subsequent opioid self-administration in rats

2019 ◽  
Author(s):  
Yayi Swain ◽  
Peter Muelken ◽  
Annika Skansberg ◽  
Danielle Lanzdorf ◽  
Zachary Haave ◽  
...  
Keyword(s):  
Individual Differences ◽  
Drug Exposure ◽  
Opioid Addiction ◽  
Self Administration ◽  
Behavioral Measures ◽  
Acute Dependence ◽  
Individual Measure ◽  
Spontaneous Withdrawal ◽  
Relationship Of ◽  
Initial Drug

AbstractUnderstanding factors contributing to individual differences in vulnerability to opioid addiction is essential for developing more effective preventions and treatments, yet few reliable behavioral predictors of subsequent opioid self-administration have been identified in rodents. Sensitivity to the acute effects of initial drug exposure predicts later addiction vulnerability in both humans and animals, but the relationship of sensitivity to withdrawal from initial drug exposure and later drug use vulnerability is unclear. The goal of the current study was to evaluate whether the degree of anhedonia experienced during withdrawal from early opioid exposure predicts subsequent vulnerability to opioid addiction. Rats were first tested for withdrawal sensitivity following acute injections of morphine (i.e., “acute dependence”), measured as elevations in intracranial self-stimulation (ICSS) thresholds (anhedonia-like behavior) during naloxone-precipitated and spontaneous withdrawal. Rats were then tested for addiction vulnerability using various measures of i.v. morphine self-administration (MSA) including acquisition, demand, extinction, and reinstatement induced by morphine, stress, and/or drug-associated cues. Greater naloxone-precipitated withdrawal across repeated morphine injections and greater peak spontaneous withdrawal severity following a single morphine injection were associated with lower addiction vulnerability on multiple MSA measures. Withdrawal-induced anhedonia predicted a wider range of MSA measures than did any individual measure of MSA itself. These data suggest that high anhedonia during withdrawal from initial opioid exposure is protective against subsequent opioid addiction vulnerability in rodents, thereby establishing one of the first behavioral measures to predict individual differences in opioid SA. This model promises to be useful for furthering our understanding of behavioral and neurobiological mechanisms underlying vulnerability to opioid addiction.

Antinociceptive Effects of VV-Hemorphin-5 Peptide Analogues Containing Aminophosphonate Moiety in Mouse Formalin Model of Pain

2020 ◽  
Vol 27 ◽  
Author(s):  
Borislav Assenov ◽  
Daniela Pechlivanova ◽  
Elena Dzhambazova ◽  
Petia Peneva ◽  
Petar Todorov
Keyword(s):  
Amino Acid ◽  
Opioid Peptides ◽  
Inflammatory Pain ◽  
Solid Phase ◽  
Antinociceptive Effect ◽  
Solid Phase Peptide Synthesis ◽  
Experimental Pain ◽  
Formalin Injection ◽  
Endogenous Opioid ◽  
Peptide Analogues

Background: Hemorphins are endogenous hemoglobin-derived peptides that belong to the family of “atypical” opioid peptides with both affinities to opioid receptors and ability to release other endogenous opioid peptides. Objective: In the present study, peptide analogues of Valorphin (VV-hemorphin-5) containing amino phosphonate moiety synthesized by solid-phase peptide synthesis (Fmoc-strategy) were investigated for their potential antinociceptive activities and compared to the reference VV-H in formalin-induced model of acute and inflammatory pain in mice. Methods: The hemorphin analogues were prepared by replacement of the one and/or two N-terminal Val in VV-hemorphin5 (VV-H) with ((dimethoxy phosphoryl) methyl)-L-valine and ((dimethoxy phosphoryl) methyl)-L-leucine to obtained the compounds pVV-H, pL-H, and pLV-H. Aiming to additionally prove the importance of amino acid valine, we introduced the ((dimethoxy phosphoryl) methyl)-L-leucine to the N-side of VV-hemorphin-5 (pLVV-H). The experiments were carried out on adult male ICR mice. All peptides were administered intracerebroventricularly at three doses (50, 25 and 12,5 µg/mouse). We have studied the effects of the peptides on acute (1st phase) and inflammatory (2nd phase) pain reaction using un experimental model with intraplantar formalin injection. Results: VV-H showed a significant antinociceptive effect both in the acute and inflammatory phases of the test. Although Valorphin hexa-, hepta-, and octapeptide analogs demonstrated a significant antinociceptive effect, they showed substantial differences considering their effective dose and the phase of the test as compared to the Valorphin. Discussion: Data showed that modified heptapeptides pVV-H and pLV-H exerted the same or better antinociception in acute and inflammatory pain, in comparison to the reference peptide, while pL-H and pLVV-H analogues were less effective. Conclusion: Our study contributes to the elucidation of the role of Valine and the number of amino acid residues in the structure of hemorphin peptide analogs in their effectiveness in suppressing both acute and inflammatory experimental pain.

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