5-O-methylcneorumchromone K Exerts Antinociceptive Effects in Mice via Interaction with GABAA Receptors

The proper pharmacological control of pain is a continuous challenge for patients and health care providers. Even the most widely used medications for pain treatment are still ineffective or unsafe for some patients, especially for those who suffer from chronic pain. Substances containing the chromone scaffold have shown a variety of biological activities, including analgesic effects. This work presents for the first time the centrally mediated antinociceptive activity of 5-O-methylcneorumchromone K (5-CK). Cold plate and tail flick tests in mice showed that the 5-CK-induced antinociception was dose-dependent, longer-lasting, and more efficacious than that induced by morphine. The 5-CK-induced antinociception was not reversed by the opioid antagonist naloxone. Topological descriptors (fingerprints) were employed to narrow the antagonist selection to further investigate 5-CK’s mechanism of action. Next, based on the results of fingerprints analysis, functional antagonist assays were conducted on nociceptive tests. The effect of 5-CK was completely reversed in both cold plate and tail-flick tests by GABAA receptor antagonist bicuculline, but not by atropine or glibenclamide. Molecular docking studies suggest that 5-CK binds to the orthosteric binding site, with a similar binding profile to that observed for bicuculline and GABA. These results evidence that 5-CK has a centrally mediated antinociceptive effect, probably involving the activation of GABAergic pathways.

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Ellagic Acid ameliorates Streptozotocin-Induced Diabetic Hyperalgesia in Rat: Involvement of Oxidative Stress

Basic and Clinical Neuroscience Journal ◽

10.32598/bcn.2021.2413.1 ◽

2021 ◽

Author(s):

Siamak Shahidi ◽

◽

Alireza Komaki ◽

Safoura Raoufi ◽

Iraj Salehi ◽

...

Keyword(s):

Oxidative Stress ◽

Ellagic Acid ◽

Therapeutic Potential ◽

Biological Activities ◽

Antinociceptive Effect ◽

Diabetic Rats ◽

Diabetic Rat ◽

Tail Flick ◽

Stress Markers ◽

Total Antioxidant

Background/Aim: Hyperalgesia is one of the current complications of diabetes mellitus that Oxidative stress and inflammation have principal role in its development. Ellagic Acid (EA) as a herbal component, has some biological activities, including antioxidant and anti-inflammatory effects. This study was designed to evaluate the possible beneficial effect of EA on hyperalgesia in streptozotocin (STZ)-induced diabetic rat. Materials and Methods: Rats were divided into control(vehicle received), diabetic, EA (25, 50 mg/kg)-treated control and EA(25, 50 mg/kg)-treated diabetic groups. Diabetes was induced by a single intraperitoneal (IP) injection of streptozotocin (STZ) (60 mg/Kg). EA was administered daily by oral gavage for 4 weeks. Hyperalgesia was assessed using tail flick (TF) and hot plate (HP) tests. Also, oxidative stress markers including malondialdehyde (MDA), total oxidant status (TOS) and total antioxidant capacity (TAC) in the serum were evaluated. Results: Diabetic animals showed marked reductions in TF and HP latencies, elevation of serum MDA level and TOS and diminution of serum TAC compared to controls significantly. Treatment of Diabetic rats with EA ameliorated reduction of TF latency at the dose of 25 mg/kg and HP latency at the dose of 50 mg/kg. Furthermore EA significantly increased TAC and decreased MDA level at dose of 50 mg/kg and reduced TOS at both doses in the serum of diabetic animals. In EA treated normal rats we could see no significant alterations in the parameters studied. Conclusion: These results displayed potent antinociceptive effect of EA in diabetic rats via attenuating oxidative stress. This proposes therapeutic potential of EA for damping diabetic hyperalgesia.

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Where are we and where to go for supportive cancer care in China? A national survey of patients and healthcare providers

10.21203/rs.3.rs-263902/v1 ◽

2021 ◽

Author(s):

Xiaotian Zhang ◽

Yiming Zhou ◽

Ting Deng ◽

Xianglin Yuan ◽

Jianping Xiong ◽

...

Keyword(s):

Supportive Care ◽

Health Care Providers ◽

Pain Treatment ◽

Nationwide Survey ◽

Multidisciplinary Teams ◽

Care Providers ◽

Supportive Cancer Care ◽

Tertiary Hospitals ◽

Oncology Care ◽

Supportive Oncology

Abstract This study aimed to make a comprehensive, nationwide survey of supportive care for cancer patients in China. Two sets of questionnaires, one for medical professionals and one for patients, were distributed. Responses were received from 12,686 medical care personnel and 11,172 patients or their family representatives from 34 provinces. It was found that only about one-fourth of caregivers felt they had much knowledge about oncology supportive care, and nearly 10% admitted to having little or no knowledge. Multidisciplinary teams for supportive care were more often available in tertiary hospitals (19.9%) than in non-tertiary hospitals (15.4%) (p < 0.05). Pain was the most common patient concern; however, pain treatment was only the fifth most common therapy administered by health care providers. Patient concerns were more often subjective (pain, economic burden, appearance, and sexual dysfunction), whereas caregiver treatments were more often directed at objective concerns (nutrition and adverse reactions to treatment regimens). Patients reported that they received no guidance or guidance only when they proposed it for psychological (25%), physical exercise (15%), nutrition (40%), or spiritual (40%-65%) needs. We conclude that the concept of supportive care is widely accepted and implemented throughout China. However, gaps exist in caregiver knowledge about supportive oncology care, the use of multidisciplinary teams, especially in non-tertiary hospitals, and the interventions between what caregivers give and what patients subjectively need. Improvements in caregiver education in supportive oncology care and the delivery of care are needed.

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Is Hippocampus Susceptible to Antinociceptive Tolerance to NSAIDs Like the Periaqueductal Grey?

Pain Research and Treatment ◽

10.1155/2014/654578 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Nana Tsiklauri ◽

Ivliane Nozadze ◽

Gulnazi Gurtskaia ◽

Merab G. Tsagareli

Keyword(s):

Dorsal Hippocampus ◽

Antinociceptive Effect ◽

Male Rats ◽

Opioid Antagonist ◽

Tail Flick ◽

Pain Models ◽

Inflammatory Drugs ◽

Antinociceptive Tolerance ◽

Undesirable Feature

Emotional distress is the most undesirable feature of painful experience. Numerous studies have demonstrated the important role of the limbic system in the affective-motivational component of pain. The purpose of this paper was to examine whether microinjection of nonsteroidal anti-inflammatory drugs (NSAIDs), Clodifen, Ketorolac, and Xefocam, into the dorsal hippocampus (DH) leads to the development of antinociceptive tolerance in male rats. We found that microinjection of these NSAIDs into the DH induces antinociception as revealed by a latency increase in the tail-flick (TF) and hot plate (HP) tests compared to controls treated with saline into the DH. Subsequent tests on consecutive three days, however, showed that the antinociceptive effect of NSAIDs progressively decreased, suggesting tolerance developed to this effect of NSAIDs. Both pretreatment and posttreatment with the opioid antagonist naloxone into the DH significantly reduced the antinociceptive effect of NSAIDs in both pain models. Our data indicate that microinjection of NSAIDs into the DH induces antinociception which is mediated via the opioid system and exhibits tolerance.

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PAIN THAT LIMITS PHYSICAL ACTIVITY AFFECTS COGNITION IN ADULTS

Innovation in Aging ◽

10.1093/geroni/igz038.2627 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S716-S716

Author(s):

Amanda F Elliott ◽

Ann Horgas

Keyword(s):

Older Adults ◽

Chronic Pain ◽

Health Care Providers ◽

Cognitive Skills ◽

Pain Treatment ◽

Medium Effect ◽

Behavioral Risk ◽

Care Providers ◽

Cross Sectional ◽

The Relationship

Abstract Reduced cognitive skills have been observed in adults with chronic pain. The purpose of this study was to explore the relationship between pain and cognition in adults utilizing a large national sample. This was a cross-sectional study employing the 2015 wave of the Behavioral Risk Factor Surveillance System (BRFSS). A total of 134,058 adults had complete data on the variables of interest for this study. Half of the sample (50%; n = 66,479) reported having joint symptoms or arthritis that was physically limiting and 16% (n = 21,976) reported having difficulty concentrating, remembering, or making decisions. Twelve percent (n = 16,537) of this sample reported having both physically limiting pain and difficulty concentrating and remembering. Chi-square analyses reveal a statistically significant association between pain and cognition in this sample [X2(1, N= 134,058) = 6925.5, p<.01], with a small to medium effect size (phi=0.227). This study provides support that pain is associated with difficulty concentrating and remembering in adults. Pain is a common persistent symptom among older adults and its effect on cognitive functioning should be noted. Effective pain treatment strategies are warranted to help reduce the cognitive burden of chronic pain. In turn, in older adults who are experiencing concentration or memory problems, health care providers should assess the individual’s pain as a possible contributor. Additional studies assessing both pain and cognition are warranted, especially looking at the relationship of these conditions over time.

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Antinociception Following Implantation of AtT-20 and Genetically Modified AtT-20/hENK Cells in Rat Spinal Cord

Journal of Neural Transplantation and Plasticity ◽

10.1155/np.1993.15 ◽

1993 ◽

Vol 4 (1) ◽

pp. 15-26 ◽

Cited By ~ 16

Author(s):

Hope H. Wu ◽

Steven C. McLoon ◽

George L. Wilcox

Keyword(s):

Spinal Cord ◽

Antinociceptive Effect ◽

Alternative Therapy ◽

Immunohistochemical Analysis ◽

Opioid Antagonist ◽

Control Group ◽

Tail Flick ◽

Rat Spinal Cord ◽

Adrenergic Agonist ◽

Spinal Subarachnoid Space

AtT-20 cells, which produceß-endorphin, and AtT-20/hENK cells, which are AtT-20 cells transfected with a proenkephalin gene, were implanted in the rat spinal subarachnoid space in an effort to produce an antinociceptive effect. Host rats were tested for antinociceptive activity by standard nociceptive tests, tail flick and hot plate. Although cell implants had minimal effect on the basal response to thermal nociceptive stimuli, administration of theß2-adrenergic agonist isoproterenol produced antinociception in the cell-implanted group but not in the control group. The antinociceptive effect of isoproterenol was dose-related and could be blocked by the opioid antagonist naloxone. Immunohistochemical analysis of spinal cords revealed the presence of enkephalin-negative cells surrounding the spinal cord of rats receiving AtT-20 cell implants, and enkephalinpositive cells surrounding the spinal cord of rats. receiving AtT-20/hENK cell implants. These results suggest that opioid-releasing cells implanted around rat spinal cord can produce antinociception and may provide an alternative therapy for chronic pain.

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The Study of Analgesic Effects of Leonurus cardiaca L. in Mice by Formalin, Tail Flick and Hot Plate Tests

International Scholarly Research Notices ◽

10.1155/2014/687697 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5 ◽

Cited By ~ 7

Author(s):

Masoume Rezaee-Asl ◽

Mandana Sabour ◽

Vahid Nikoui ◽

Sattar Ostadhadi ◽

Azam Bakhtiarian

Keyword(s):

Biological Activities ◽

Antinociceptive Effect ◽

Intraperitoneal Administration ◽

Ethanolic Extract ◽

Antimicrobial Activities ◽

Tail Flick ◽

Nociceptive Response ◽

Alcoholic Extract ◽

Hot Plate ◽

Leonurus Cardiaca

Leonurus cardiaca, commonly known as motherwort, is a member of the Lamiaceae family. It has a number of interesting biological activities, for example, sedative and hypotensive, antioxidant, anti-inflammatory, and antimicrobial activities. The aim of the present study was to investigate the effect of alcoholic extract of aerial part of Leonurus cardiaca on nociceptive response using formalin, tail flick, and hot plate tests in mice. The acute treatment of mice with an ethanolic extract at doses of 500 and 250 mg/kg by intraperitoneal administration produced a significant antinociceptive in the first and second phases of formalin test, respectively. The hot plate and tail flick tests showed an increase in the antinociceptive effect at dose 500 mg/kg. These results suggest that Leonurus cardiaca possesses central and peripheral antinociceptive actions.

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Unusual Drugs of Abuse in Chronic Pain Patients

10.2310/pm.15085 ◽

2017 ◽

Author(s):

Alan D. Kaye ◽

Elyse Cornett ◽

Charles Fox ◽

Shilpadevi Patil ◽

Harish Siddaiah ◽

...

Keyword(s):

Health Care ◽

Chronic Pain ◽

Drug Abuse ◽

Health Care Providers ◽

Drugs Of Abuse ◽

Pain Treatment ◽

The United States ◽

Care Providers ◽

Chronic Pain Patients ◽

Pain Patients

Chronic pain occurs in one third of the American population. Management of chronic pain is a growing area in health care; however, there is a dilemma for health care providers to treat the chronic pain of individuals who have known current or suspected drug abuse or addiction. Even if the individual is not addicted to opiates or prescription pain medications, it is possible to become addicted to a new substance. The National Institutes of Health considers drug addiction a neurophysiologic disease, and as of 2014, 24.6 million people in the United States abuse drugs. As more patients are seeking treatment for chronic pain, health care providers are seeing an increase in patients who have a history of drug abuse or addiction, and it is imperative that health care providers are aware of how best to care for these patients. This review discusses chronic pain and the drugs that are typically used to treat chronic pain, as well as drugs that have been reported to be abused in chronic pain patients. There are limited or no data available on the more recent designer drugs, such as bath salts, K2 (spice), and even common drugs of abuse, such as methylenedioxymethamphetamine (MDMA). More research should be conducted on what drugs are abused in chronic pain patients, especially nonopioid drugs such as stimulants. This information would help educate health care providers and create better pain treatment regimens for patients who abuse drugs. Key words: chronic pain, drug abuse, marijuana, methamphetamine, opioids

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Is It “True” Pain? Pain Treatment Discharge Planning for Seriously Injured Patients

Ethnicity & Disease ◽

10.18865/ed.31.1.139 ◽

2021 ◽

Vol 31 (1) ◽

pp. 139-148

Author(s):

Shoshana V. Aronowitz ◽

Therese S. Richmond ◽

Peggy Compton ◽

Sara F. Jacoby

Keyword(s):

Health Care ◽

Health Care Providers ◽

Nurse Practitioners ◽

Trauma Care ◽

Pain Treatment ◽

Physician Assistants ◽

The United States ◽

Opioid Overdose ◽

Care Providers ◽

Injured Patients

Background: The United States is experiencing an opioid overdose crisis accounting for as many as 130 deaths per day. As a result, health care providers are increasingly aware that prescribed opioids can be misused and diverted. Prescription of pain medication, including opioids, can be influenced by how health care providers perceive the trustworthiness of their patients. These perceptions hinge on a multiplicity of characteristics that can include a patient’s race, ethnicity, gender, age, and presenting health condition or injury. The purpose of this study was to identify how trauma care providers evaluate and plan hospital discharge pain treatment for patients who survive serious injuries.Methods: Using a semi-structured guide from November 2018 to January 2019, we interviewed 12 providers (physicians, nurse practitioners, physician assistants) who prescribe discharge pain treatment for injured patients at a trauma center in Philadelphia, PA. We used thematic analysis to interpret these data.Results: Participants identified the importance of determining “true” pain, which was the overarching theme that emerged in analysis. Subthemes included perceptions of the influence of reliable methods for pain assessment, the trustworthiness of their patient population, and the consequences of not getting it right.Conclusions: Trauma care providers described a range of factors, beyond patient-elicited pain reports, in order to interpret their patients’ analgesic needs. These included consideration of both the risks of under treatment and unnecessary suffering, and overtreatment and contribution to opioid overdoses.Ethn Dis. 2021;31(1):139- 148; doi:10.18865/ed.31.1.139

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