scholarly journals Cannabinoids in Chronic Pain: Therapeutic Potential Through Microglia Modulation

2022 ◽  
Vol 15 ◽  
Author(s):  
Nynke J. van den Hoogen ◽  
Erika K. Harding ◽  
Chloé E. D. Davidson ◽  
Tuan Trang
Keyword(s):  
Chronic Pain ◽  
Immune Cells ◽  
Therapeutic Potential ◽  
Emotional Experience ◽  
Opioid Analgesics ◽  
Pain Modulation ◽  
Pain Outcomes ◽  
Cb2 Receptors ◽  
Affective Components ◽  
Peripheral Immune Cells

Chronic pain is a complex sensory, cognitive, and emotional experience that imposes a great personal, psychological, and socioeconomic burden on patients. An estimated 1.5 billion people worldwide are afflicted with chronic pain, which is often difficult to treat and may be resistant to the potent pain-relieving effects of opioid analgesics. Attention has therefore focused on advancing new pain therapies directed at the cannabinoid system because of its key role in pain modulation. Endocannabinoids and exogenous cannabinoids exert their actions primarily through Gi/o-protein coupled cannabinoid CB1 and CB2 receptors expressed throughout the nervous system. CB1 receptors are found at key nodes along the pain pathway and their activity gates both the sensory and affective components of pain. CB2 receptors are typically expressed at low levels on microglia, astrocytes, and peripheral immune cells. In chronic pain states, there is a marked increase in CB2 expression which modulates the activity of these central and peripheral immune cells with important consequences for the surrounding pain circuitry. Growing evidence indicate that interventions targeting CB1 or CB2 receptors improve pain outcomes in a variety of preclinical pain models. In this mini-review, we will highlight recent advances in understanding how cannabinoids modulate microglia function and its implications for cannabinoid-mediated analgesia, focusing on microglia-neuron interactions within the spinal nociceptive circuitry.

scholarly journals Receptor and Molecular Targets for the Development of Novel Opioid and Non-Opioid Analgesic Therapies

2021 ◽  
pp. 153-163
Keyword(s):  
Chronic Pain ◽  
Key Words ◽  
Cannabinoid Receptors ◽  
Transient Receptor Potential ◽  
Therapeutic Potential ◽  
Opioid Analgesic ◽  
Opioid Analgesics ◽  
Transient Receptor Potential Vanilloid ◽  
Nociceptive Transmission ◽  
Pubmed Database

BACKGROUND: Although conventional pain relief therapeutics have centered around μ-opioid agonists, these drugs are limited by adverse side effects, including respiratory depression and addiction potential. The ongoing opioid epidemic has galvanized research into novel analgesic therapies with more favorable profiles. New pharmacologic agents have been developed to target neuronal pathways involved in pain sensation. Certain receptors have been recognized to mediate nociceptive transmission, central sensitization, and the development of chronic pain states. OBJECTIVES: We conducted a literature review to identify potential targets for novel analgesic therapies. STUDY DESIGN: This study is a narrative review of potential analgesic targets. We characterize their antinociceptive mechanisms of action and evaluate their therapeutic potential. METHODS: A systemized search of available literature on novel analgesics was performed. A search was performed through the PubMed database to identify articles with key words of “novel analgesics,” “novel non-opioid analgesics,” “novel pain targets,” and “non-opioid analgesics.” Potential drug classes were identified and researched through corresponding keywords, with an emphasis on publications from 2018 to 2020. Older articles were included if frequently referenced by current literature. RESULTS: Potential novel analgesic targets include Nav1.7, Nav1.8, CaV2.2, and transient receptor potential vanilloid-1 (TRPV1) cation channel receptors in the peripheral nervous system. Other approaches disrupt the synthesis of pronociceptive signaling molecules such as nitric oxide, prostaglandin E2, and interleukin-6 (IL-6). Within central pain pathways, modification of -opioid, -opioid, N-methyl-D-aspartate, and cannabinoid receptors have been investigated in chronic pain and hyperalgesia models. Recent advances in molecular technology have also presented opportunities to modify protein expression or the cellular genome altogether. LIMITATIONS: Several analgesic targets have only demonstrated efficacy in preclinical trials. There are limited data evaluating the long-term safety profiles of therapies further on in development. CONCLUSIONS: We provide an overview of potential analgesic therapies in various stages of development, which may become clinically relevant in the near future. Some drugs such as TRPV1 agonists, anti-IL-6, and anti-nerve growth factor antibodies have demonstrated analgesic effect in specific clinical pain states. KEY WORDS: Nav1.7, Cav2.2, TRPV1, mPGES-1, IL-6, FAAH, NGF, gene therapy

scholarly journals Manajemen Nyeri Kronis pada Kehamilan

2020 ◽  
Vol 2 (1) ◽  
pp. 48-62
Author(s):  
Budi Yulianto Sarim ◽  
Bambang Suryono
Keyword(s):  
Chronic Pain ◽  
Tissue Damage ◽  
International Association ◽  
Emotional Experience ◽  
Opioid Analgesics ◽  
Pelvic Girdle ◽  
Pelvic Girdle Pain ◽  
Pharmacological Management ◽  
Mechanical Factors ◽  
In Pregnancy

Menurut IASP ( International Association of the Study of Pain) nyeri didefinisikan sebagai “an unpleasant sensory and emotional experience associated with actual or potential tissue damage or describe interm of such damage”. Nyeri adalah rasa inderawi dan pengalaman emosional yang tidak menyenangkan akibat adanya kerusakan jaringan yang nyata atau yang berpotensi rusak atau sesuatu yang tergambarkan seperti itu.Kelainan muskuloskeletal yang sering dialami oleh wanita hamil adalah berupa nyeri lumbopelvis pada kehamilan (pelvic girdle pain) dan nyeri kronis lumbal (low back pain).Adapun yang menyebabnya adalah faktor hormonal, faktor mekanis dan vaskuler. Manajemen untuk nyeri kronis pada wanita hamil dapat dilakukan melalui manajemen non farmakologis dan manajemen farmakologis. Manajemen non farmakologis dapat dikerjakan dengan cara fisioterapi, terapi distraksi, terapi musik, guided imaginary dan relaksasi. Untuk manajemen farmakologis, obat – obatan yang dapat diberikan adalah asetaminofen, NSAID dan analgesik opioid.   Management Chronic Pain in Pregnancy Abstract According to the IASP (International Association of the Study of Pain) pain is defined as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage or describe the interim of such damage". Pain is a sensation and or emotional experience unpleasant and disturbing as a result of tissue damage, or potential tissue damage. Musculoskeletal disorders are often experienced by pregnant women is pelvic girdle pain and chronic pain lumbar. The etiology of that is the hormonal factor, mechanical factors and vascular factors. Management of chronic pain in pregnancy can be done through non-pharmacological management and pharmacological management. Non pharmacological management can be done by means of physiotherapy, distraction therapy, music therapy, guided imaginary and relaxation. For pharmacological management can be given is acetaminophen, NSAIDs and opioid analgesics.

scholarly journals Hypothesizing in the Face of the Opioid Crisis Coupling Genetic Addiction Risk Severity (GARS) Testing with Electrotherapeutic Nonopioid Modalities Such as H-Wave Could Attenuate Both Pain and Hedonic Addictive Behaviors

2022 ◽  
Vol 19 (1) ◽  
pp. 552
Author(s):  
Ashim Gupta ◽  
Abdalla Bowirrat ◽  
Luis Llanos Gomez ◽  
David Baron ◽  
Igor Elman ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Opioid Analgesics ◽  
The United States ◽  
Opioid Overdose ◽  
Addictive Behaviors ◽  
Pain Clinics ◽  
Analgesic Agents ◽  
Addiction Risk ◽  
Affective Components

In the United States, amid the opioid overdose epidemic, nonaddicting/nonpharmacological proven strategies are available to treat pain and manage chronic pain effectively without opioids. Evidence supporting the long-term use of opioids for pain is lacking, as is the will to alter the drug-embracing culture in American chronic pain management. Some pain clinicians seem to prefer classical analgesic agents that promote unwanted tolerance to analgesics and subsequent biological induction of the “addictive brain”. Reward genes play a vital part in modulation of nociception and adaptations in the dopaminergic circuitry. They may affect various sensory and affective components of the chronic pain syndromes. The Genetic Addiction Risk Severity (GARS) test coupled with the H-Wave at entry in pain clinics could attenuate pain and help prevent addiction. The GARS test results identify high-risk for both drug and alcohol, and H-Wave can be initiated to treat pain instead of opioids. The utilization of H-Wave to aid in pain reduction and mitigation of hedonic addictive behaviors is recommended, notwithstanding required randomized control studies. This frontline approach would reduce the possibility of long-term neurobiological deficits and fatalities associated with potent opioid analgesics.

scholarly journals A novel role for CCR3 in brain T-cell infiltration and cognition in aging

2021 ◽  
Author(s):  
Arnaud Teichert ◽  
Sanket Rege ◽  
Juliet Masumi ◽  
Lily Akrapongpisak ◽  
Hannah Hackbart ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Cells ◽  
Therapeutic Strategy ◽  
Therapeutic Potential ◽  
Direct Action ◽  
T Cell Infiltration ◽  
Age Related ◽  
Immune Mediated ◽  
Cognitive Benefits ◽  
Peripheral Immune Cells

Abstract Targeting immune-mediated, age-related, biology has the potential to be a transformative therapeutic strategy. However, the redundant nature of the multiple cytokines that change with aging requires identification of a master downstream regulator to successfully exert therapeutic efficacy. Here, we discovered CCR3 as a prime candidate, and inhibition of CCR3 has profound pro-cognitive benefits, but these benefits are not driven by an obvious direct action on CNS-resident cells. Instead, CCR3-expressing cells in the periphery that are modulated in aging inhibit infiltration of T cells across the blood-brain barrier and reduce neuroinflammation. The axis of CCR3-expressing peripheral immune cells influencing crosstalk from periphery to brain provides a novel and therapeutically tractable link. These findings indicate the broad therapeutic potential of CCR3 inhibition in a spectrum of neuroinflammatory diseases of aging.

scholarly journals Immune Actions on the Peripheral Nervous System in Pain

2021 ◽  
Vol 22 (3) ◽  
pp. 1448
Author(s):  
Jessica Aijia Liu ◽  
Jing Yu ◽  
Chi Wai Cheung
Keyword(s):  
Chronic Pain ◽  
Nervous System ◽  
Peripheral Nervous System ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Process Integration ◽  
Current Knowledge ◽  
Therapeutic Strategies ◽  
Lipid Mediators ◽  
Cellular Changes

Pain can be induced by tissue injuries, diseases and infections. The interactions between the peripheral nervous system (PNS) and immune system are primary actions in pain sensitizations. In response to stimuli, nociceptors release various mediators from their terminals that potently activate and recruit immune cells, whereas infiltrated immune cells further promote sensitization of nociceptors and the transition from acute to chronic pain by producing cytokines, chemokines, lipid mediators and growth factors. Immune cells not only play roles in pain production but also contribute to PNS repair and pain resolution by secreting anti-inflammatory or analgesic effectors. Here, we discuss the distinct roles of four major types of immune cells (monocyte/macrophage, neutrophil, mast cell, and T cell) acting on the PNS during pain process. Integration of this current knowledge will enhance our understanding of cellular changes and molecular mechanisms underlying pain pathogenies, providing insights for developing new therapeutic strategies.

scholarly journals Profiles of Peripheral Immune Cells of Uncomplicated COVID-19 Cases with Distinct Viral RNA Shedding Periods

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 514
Author(s):  
Denise Utami Putri ◽  
Cheng-Hui Wang ◽  
Po-Chun Tseng ◽  
Wen-Sen Lee ◽  
Fu-Lun Chen ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Cells ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Severe Disease ◽  
Viral Rna ◽  
Disease Course ◽  
Peripheral Blood Mononuclear ◽  
Peripheral Immune Cells ◽  
Cell Profile

The heterogeneity of immune response to COVID-19 has been reported to correlate with disease severity and prognosis. While so, how the immune response progress along the period of viral RNA-shedding (VRS), which determines the infectiousness of disease, is yet to be elucidated. We aim to exhaustively evaluate the peripheral immune cells to expose the interplay of the immune system in uncomplicated COVID-19 cases with different VRS periods and dynamic changes of the immune cell profile in the prolonged cases. We prospectively recruited four uncomplicated COVID-19 patients and four healthy controls (HCs) and evaluated the immune cell profile throughout the disease course. Peripheral blood mononuclear cells (PBMCs) were collected and submitted to a multi-panel flowcytometric assay. CD19+-B cells were upregulated, while CD4, CD8, and NK cells were downregulated in prolonged VRS patients. Additionally, the pro-inflammatory-Th1 population showed downregulation, followed by improvement along the disease course, while the immunoregulatory cells showed upregulation with subsequent decline. COVID-19 patients with longer VRS expressed an immune profile comparable to those with severe disease, although they remained clinically stable. Further studies of immune signature in a larger cohort are warranted.

scholarly journals Brain-Derived Neurotrophic Factor and Immune Cells in Osteoarthritis, Chronic Low Back Pain, and Chronic Widespread Pain Patients: Association with Anxiety and Depression

Medicina ◽  
2021 ◽  
Vol 57 (4) ◽  
pp. 327
Author(s):  
Dominique Josephine Dimmek ◽  
Christoph Korallus ◽  
Sabine Buyny ◽  
Gutenbrunner Christoph ◽  
Ralf Lichtinghagen ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Low Back Pain ◽  
Back Pain ◽  
Immune Cells ◽  
Chronic Widespread Pain ◽  
Anxiety And Depression ◽  
Low Back ◽  
Widespread Pain ◽  
Chronic Pain Patients ◽  
Pain Patients

Background and Objectives: Musculoskeletal dysfunction can induce several types of chronic pain syndromes. It is of particular interest to elucidate the pathomechanism of different forms of chronic pain. It is possible that patients who have developed chronic widespread pain (CWP) may endure different pathomechanisms as compared to those who suffer from local pain (osteoarthritis, OA) and regional pain (chronic low back pain, cLBP), especially with regard to pain regulation and its related biomediators. The aim of this study was to determine the differences in pathomechanisms among these patients by measuring pain-related biomediators, particularly brain-derived neurotrophic factor (BDNF). Additionally, subpopulations of immune cells were determined in parallel. Materials and Methods: Patients and healthy subjects (HSs) were recruited (age and gender-matched). BDNF was measured from serum samples of patients and HSs and the data of body composition parameters were recorded. Additionally, both patients and HSs were asked to fill in questionnaires related to pain intensity, anxiety, and depression. Results: Our results highlight that the levels of both free and total BDNF are significantly lower in pain patients compared to HSs, with p values of 0.041 and 0.024, respectively. The number of CD3− CD56bright natural killer (NK) cells shows significant differences between the groups. Comparing all chronic pain patients with HSs reveals a significantly lower number of CD4+ CD8+ T cells (p = 0.031), CD3− CD56bright NK cells (p = 0.049) and CD20+ CD3− cells (p = 0.007). Conclusions: To conclude, it seems that a general conformity between the pathomechanisms of different chronic pain diseases exists, although there are unique findings only in specific chronic pain patients.

scholarly journals AB0953 CANNABINOIDS: FRIEND OR FOE OR A BYSTANDER?

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1774.2-1774
Author(s):  
N. Jain ◽  
N. Reddy ◽  
A. Moorthy
Keyword(s):  
Chronic Pain ◽  
Complementary Medicine ◽  
Health Care Professionals ◽  
Primary Care Physicians ◽  
Therapeutic Potential ◽  
Current Therapy ◽  
Common Diagnosis ◽  
Patient Reported ◽  
Ongoing Pain ◽  
Primary Physicians

Background:Cannabinoids has recently gained popularity for use in chronic pain. There is a lot of inquisitiveness among our patients wherein health care professionals are asked about its efficacy, side effects and sometimes even ask for a prescription! As there is paucity of data and research about its use in rheumatology, patient reported outcome(PROM) can guide ahead in expanding our knowledge and experience.Objectives:To study usage of cannabinoids by rheumatology patientsTo study awareness among primary physicians regarding Cannabinoid usage in rheumatology.Methods:Cross sectional survey with two arms. Arm 1 Information from patients attending tertiary rheumatology clinic,including perception regarding the use of Cannabinoids.Arm 2 consisted of collecting data via web-based survey with20-question from 100 GPs of Leicestershire. Questions on demographics, perspectives on and knowledge of cannabinoid use. Statistical analysis SPSS software.Results:Arm1 Total 102 rheumatology patients with 60%were females and 45% secondary education. 48% were unemployed. 75% Caucasians, 18% Asians. RA most common diagnosis followed by OA and FMS. 40 % depression and anxiety in addition to Rheumatic disease. 94% reported ongoing pain with 6-8 on a VAS scale. 79% were satisfied with their current therapy. 65% had heard about complementary medicine and 15% reported using cannabinoids.Most common form Cannabinoids oil 60% followed by smoking 20%. 56% reported using >3 months and majority 72% use daily. Median age 55 years. 88% users Caucasians. Mean disease duration 6.25 years among users indicates chronicity of disease has a direct proportion in usage. All users had ongoing pain of 7 on VAS. 87% believed it helps them managing pain effectively with a pain free state. On an average spends between 50-100 pounds per week. More than half believe cannabinoids should be available as a prescription drug in NHS and 30% interested to know more about it.In Arm 2 consisting of Primary care physicians, response rate 50%. Average clinical experience 5 years. Only 20% heard about usage of complementary medicine by rheumatology patient. Most replied that 10% of their patients use Cannabinoids for pain management. Most did not believe use of cannabinoids benefited the patients. Only 4% recommend its usage. 25% think it should be available as prescription. 40% experienced patients asking about cannabinoids during appointment. 88% of respondents did not know much about cannabinoid usage in rheumatology and have never prescribed it in their practice.Conclusion:Cannabinoids widely used by the rheumatology patients with PROM favouring its efficacy for control of chronic pain. Preclinical data suggest that cannabinoids might have a therapeutic potential RA1, OA, FMS2. Clinical data regarding cannabinoid treatment for rheumatic diseases are scarce, therefore, recommendations concerning cannabinoid treatment cannot be made. All patients who reported using it suffered from moderate to severe chronic pain. Thus main indication of usage was pain rather than recreational purpose. Although a small survey it clearly highlights lack of knowledge among primary physicians. These results emphasise the need for further research regarding the benefits and risks of cannabinoids in rheumatology.References:[1]RichardsonD. etal Characterisation ofthe cannabinoid receptor system in synovial tissue andfluid in patients with OA and RA Arthritis Res.Ther. 10, R43 (2008).[2]Walitt, B etal Cannabinoids for fibromyalgia. Cochrane DatabaseSyst. Rev. 7, CD011694 (2016).Disclosure of Interests:Nibha Jain: None declared, Neelima Reddy: None declared, Arumugam Moorthy Speakers bureau: Abbvie, Novartis,UCB,MSD

Sleep disturbance in patients attending specialized chronic pain clinics in Denmark: a longitudinal study examining the relationship between sleep and pain outcomes

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Henrik Bjarke Vaegter ◽  
Mette Terp Høybye ◽  
Frederik Hjorth Bergen ◽  
Christine E. Parsons
Keyword(s):  
Quality Of Life ◽  
Chronic Pain ◽  
Sleep Quality ◽  
Pain Intensity ◽  
Sleep Disturbances ◽  
Pain Disability ◽  
Pain Clinics ◽  
Pain Outcomes

Abstract Objectives Sleep disturbances are highly prevalent in patients with chronic pain. However, the majority of studies to date examining sleep disturbances in patients with chronic pain have been population-based cross-sectional studies. The aims of this study were to 1) examine the frequency of sleep disturbances in patients referred to two interdisciplinary chronic pain clinics in Denmark, 2) explore associations between sleep disturbances and pain intensity, disability and quality of life at baseline and follow-up, and 3) explore whether changes in sleep quality mediated the relationships between pain outcomes at baseline and pain outcomes at follow-up. Methods We carried out a longitudinal observational study, examining patients enrolled in two chronic pain clinics assessed at baseline (n=2,531) and post-treatment follow-up (n=657). Patients reported on their sleep disturbances using the sleep quality subscale of the Karolinska Sleep Questionnaire (KSQ), their pain intensity using 0–10 numerical rating scales, their pain-related disability using the Pain Disability Index (PDI), and quality of life using the EuroQol-VAS scale. The average time between baseline and follow-up was 207 days (SD=154). Results At baseline, the majority of patients reported frequent sleep disturbances. We found a significant association at baseline between self-reported sleep disturbances and pain intensity, pain-related disability, and quality of life, where greater sleep disturbance was associated with poorer outcomes. At follow-up, patients reported significant improvements across all pain and sleep outcomes. In two mediation models, we showed that changes in sleep disturbances from baseline to follow-up were significantly associated with (i) pain intensity at follow-up, and (ii) pain disability at follow-up. However, baseline pain intensity and disability scores were not associated with changes in sleep disturbances and, we did not find evidence for significant mediation of either pain outcome by changes in sleep disturbances. Conclusions Self-reported sleep disturbances were associated with pain outcomes at baseline and follow-up, with greater sleep disturbances associated with poorer pain outcomes. Changes in sleep quality did not mediate the relationships between baseline and follow-up scores for pain intensity and disability. These findings contribute to a growing body of evidence confirming an association between sleep and chronic pain experience, particularly suggestive of a sleep to pain link. Our data following patients after interdisciplinary treatment suggests that improved sleep is a marker for a better outcome after treatment.

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