Protective role of neuronal and lymphoid cannabinoid CB2 receptors in neuropathic pain

AbstractCannabinoid CB2 receptor (CB2r) agonists are potential painkillers void of psychotropic effects. Peripheral immune cells, neurons and glia express CB2r, however the involvement of CB2r from these cells in neuropathic pain remains unresolved. We explored spontaneous neuropathic pain through on-demand self-administration of the selective CB2r agonist JWH133 in wild-type and knockout mice lacking CB2r in neurons, monocytes or constitutively. Operant self-administration reflected drug-taking to alleviate spontaneous pain, nociceptive and affective manifestations. While constitutive deletion of CB2r disrupted JWH133-taking behavior, this behavior was not modified in monocyte-specific CB2r knockouts and was increased in mice defective in neuronal CB2r knockouts suggestive of increased spontaneous pain. Interestingly, CB2r-positive lymphocytes infiltrated the injured nerve and possible CB2r transfer from immune cells to neurons was found. Lymphocyte CB2r depletion also exacerbated JWH133 self-administration and inhibited antinociception. This work identifies a simultaneous activity of neuronal and lymphoid CB2r that protects against spontaneous and evoked neuropathic pain.

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Protective role of neuronal and lymphoid cannabinoid CB2 receptors in neuropathic pain

eLife ◽

10.7554/elife.55582 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 2

Author(s):

David Cabañero ◽

Angela Ramírez-López ◽

Eva Drews ◽

Anne Schmöle ◽

David M Otte ◽

...

Keyword(s):

Neuropathic Pain ◽

Immune Cells ◽

Protective Role ◽

Spontaneous Pain ◽

Wild Type ◽

Self Administration ◽

Psychotropic Effects ◽

Peripheral Immune Cells ◽

Simultaneous Activity

Cannabinoid CB2 receptor (CB2) agonists are potential analgesics void of psychotropic effects. Peripheral immune cells, neurons and glia express CB2; however, the involvement of CB2 from these cells in neuropathic pain remains unresolved. We explored spontaneous neuropathic pain through on-demand self-administration of the selective CB2 agonist JWH133 in wild-type and knockout mice lacking CB2 in neurons, monocytes or constitutively. Operant self-administration reflected drug-taking to alleviate spontaneous pain, nociceptive and affective manifestations. While constitutive deletion of CB2 disrupted JWH133-taking behavior, this behavior was not modified in monocyte-specific CB2 knockouts and was increased in mice defective in neuronal CB2 knockouts suggestive of increased spontaneous pain. Interestingly, CB2-positive lymphocytes infiltrated the injured nerve and possible CB2transfer from immune cells to neurons was found. Lymphocyte CB2depletion also exacerbated JWH133 self-administration and inhibited antinociception. This work identifies a simultaneous activity of neuronal and lymphoid CB2that protects against spontaneous and evoked neuropathic pain.

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Protective role of berberine on ulcerative colitis through modulating enteric glial cells–intestinal epithelial cells–immune cells interactions

Acta Pharmaceutica Sinica B ◽

10.1016/j.apsb.2019.08.006 ◽

2020 ◽

Vol 10 (3) ◽

pp. 447-461 ◽

Cited By ~ 10

Author(s):

Heng Li ◽

Chen Fan ◽

Huimin Lu ◽

Chunlan Feng ◽

Peilan He ◽

...

Keyword(s):

Ulcerative Colitis ◽

Epithelial Cells ◽

Glial Cells ◽

Immune Cells ◽

Intestinal Epithelial Cells ◽

Protective Role ◽

Intestinal Epithelial ◽

Enteric Glial Cells

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Circadian Clock Regulates Inflammation and the Development of Neurodegeneration

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.696554 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xiao-Lan Wang ◽

Lianjian Li

Keyword(s):

Circadian Clock ◽

Immune Cells ◽

Brain Function ◽

Cellular Tissue ◽

Physiological Processes ◽

Circadian Control ◽

Prevention And Treatment ◽

Potential Strategy ◽

Peripheral Immune Cells

The circadian clock regulates numerous key physiological processes and maintains cellular, tissue, and systemic homeostasis. Disruption of circadian clock machinery influences key activities involved in immune response and brain function. Moreover, Immune activation has been closely linked to neurodegeneration. Here, we review the molecular clock machinery and the diurnal variation of immune activity. We summarize the circadian control of immunity in both central and peripheral immune cells, as well as the circadian regulation of brain cells that are implicated in neurodegeneration. We explore the important role of systemic inflammation on neurodegeneration. The circadian clock modulates cellular metabolism, which could be a mechanism underlying circadian control. We also discuss the circadian interventions implicated in inflammation and neurodegeneration. Targeting circadian clocks could be a potential strategy for the prevention and treatment of inflammation and neurodegenerative diseases.

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Role of Peripheral Immune Cells-Mediated Inflammation on the Process of Neurodegenerative Diseases

Frontiers in Immunology ◽

10.3389/fimmu.2020.582825 ◽

2020 ◽

Vol 11 ◽

Author(s):

Qiuyu Yang ◽

Guoqing Wang ◽

Feng Zhang

Keyword(s):

Neurodegenerative Diseases ◽

Immune Cells ◽

Peripheral Immune Cells

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The role of peripheral immune cells in the CNS in steady state and disease

Nature Neuroscience ◽

10.1038/nn.4475 ◽

2017 ◽

Vol 20 (2) ◽

pp. 136-144 ◽

Cited By ~ 193

Author(s):

Marco Prinz ◽

Josef Priller

Keyword(s):

Steady State ◽

Immune Cells ◽

Peripheral Immune Cells

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The attenuation of pain behaviour and serum interleukin-6 concentration by nimesulide in a rat model of neuropathic pain

Scandinavian Journal of Pain ◽

10.1016/j.sjpain.2010.08.003 ◽

2010 ◽

Vol 1 (4) ◽

pp. 229-234 ◽

Cited By ~ 5

Author(s):

Taraneh Moini Zanjani ◽

Masoumeh Sabetkasaei ◽

Behnaz Karimian ◽

Farzaneh Labibi ◽

Babak Farokhi ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Neuropathic Pain ◽

Immune System ◽

Immune Cells ◽

Interleukin 6 ◽

Inflammatory Responses ◽

Pain Behaviour ◽

Behavioural Tests

AbstractBackgroundEvidence for a role of immune system in hyperalgesic pain states is increasing. Recent work in neuroimmunology suggests that the immune system does more than simply perform its well known functions of recognizing and removing invading pathogens and tumors. Interest in neuroinflammation and neuroimmune activation has grown rapidly in recent years with the recognition of the role of central nervous system inflammatiom and immune responses in the aetiology of pain states. Among various theories, the role of inflammatory responses of the injured nerve has recently received attention. Cytokines are heterogenous group of polypeptides that activate the immune system and mediate inflammatory responses, acting on a variety of tissue, including the peripheral and central nervous system. Interleukin-6 (IL-6) a pro-inflammatory cytokine, is potentially important in pain aetiology, have pronociceptive actions. Neuropathic pain may be due to a primary insult to the peripheral or central nervous system. Substances released during inflammation from immune cells play an important role in the development and maintenance of chronic pain. Nimesulide, a highly selective cox-2 inhibitor, effectively reduces hyperalgesia due to peripherally administration of inflammatory agents like formalin. The safety of nimesulide was reported for some conditions in which other NSAIDs are contraindicated. Here we have determined the effect of nimesulide on pain behaviour and serum IL-6 level in chronic constriction injury (CCI) model of neuropathic pain.MethodsExperiments were carried out on male Wistar rats, (weight 150–200 g, n = 8). Rats were divided into 3 different groups: 1-CCI + saline 0.9% 2Sham + saline 0.9% (control) 3CCI + drug. Nimesulide (1.25, 2.5, 5 mg/kg, i.p.) was injected 1h before surgery and continued daily to day 14 post-ligation. 42 °C water for thermal hyperalgesia, von Frey filaments for mechanical allodynia, acetone test for cool allodynia and 10 °C water for cold hyperalgesia were respectively used as pain behavioural tests. Behavioural tests were recorded before surgery and on postoperative days 1, 3, 5, 7, 10, 14 and the serum concentration of IL-6 was determined at the day 14.ResultsThe results of this study showed a decrease in hyperalgesia and allodynia following nimesulide administration.ConclusionsIt appears that nimesulide was able to reduce pain behaviour due to nerve inflammation and a parallel decrease in the serum IL-6 concentration was observed.ImplicationsThe immune system is an important mediator in the cascade of events that ultimately results in hyperalgesia. Cytokines contribute to the patheogenesis of neuropathic pain, therefore drugs that inhibit cytokine release from immune cells may reduce inflammatory pain states.

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Author response: Protective role of neuronal and lymphoid cannabinoid CB2 receptors in neuropathic pain

10.7554/elife.55582.sa2 ◽

2020 ◽

Author(s):

David Cabañero ◽

Angela Ramírez-López ◽

Eva Drews ◽

Anne Schmöle ◽

David M Otte ◽

...

Keyword(s):

Neuropathic Pain ◽

Protective Role ◽

Author Response ◽

Cb2 Receptors ◽

Cannabinoid Cb2 Receptors

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Lactoferrin and oral pathologies: a therapeutic treatment

Biochemistry and Cell Biology ◽

10.1139/bcb-2020-0052 ◽

2020 ◽

pp. 1-10

Author(s):

Luigi Rosa ◽

Maria Stefania Lepanto ◽

Antimo Cutone ◽

Giusi Ianiro ◽

Stefania Pernarella ◽

...

Keyword(s):

Topical Administration ◽

Protective Role ◽

Pathogenic Microorganisms ◽

Protective Function ◽

Maxillary Bone ◽

Abiotic Surfaces ◽

Bone Damage ◽

Aerobic And Anaerobic ◽

Simultaneous Activity

The oral cavity is a non-uniform, extraordinary environment characterized by mucosal, epithelial, abiotic surfaces and secretions as saliva. Aerobic and anaerobic commensal and pathogenic microorganisms colonize the tongue, teeth, jowl, gingiva, and periodontium. Commensals exert an important role in host defenses, while pathogenic microorganisms can nullify this protective function causing oral and systemic diseases. Every day, 750–1000 mL of saliva, containing several host defense constituents including lactoferrin (Lf), are secreted and swallowed. Lf is a multifunctional iron-chelating cationic glycoprotein of innate immunity. Depending on, or regardless of its iron-binding ability, Lf exerts bacteriostatic, bactericidal, antibiofilm, antioxidant, antiadhesive, anti-invasive, and anti-inflammatory activities. Here, we report the protective role of Lf in different oral pathologies, such as xerostomia, halitosis, alveolar or maxillary bone damage, gingivitis, periodontitis, and black stain. Unlike antibiotic therapy, which is ineffective against bacteria that are within a biofilm, adherent, or intracellular, the topical administration of Lf, through its simultaneous activity against microbial replication, biofilms, adhesion, and invasiveness, as well as inflammation, has been proven to be efficient in the treatment of all known oral pathologies without any adverse effects.

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