Involvement of neutrophils and interleukin-18 in nociception in a mouse model of muscle pain

Yoshida, Shinichirou; Hagiwara, Yoshihiro; Tsuchiya, Masahiro; Shinoda, Masamichi; Koide, Masashi; Hatakeyama, Hiroyasu; Chaweewannakorn, Chayanit; Yano, Toshihisa; Sogi, Yasuhito; Itaya, Nobuyuki; Sekiguchi, Takuya; Yabe, Yutaka; Sasaki, Keiichi; Kanzaki, Makoto; Itoi, Eiji

doi:10.1177/1744806918757286

Cited by 24 publications

(26 citation statements)

References 50 publications

(91 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, excessive PMN responses may contribute to ongoing inflammation and tissue damage in a number of diseases and ailments [32,33,34,35]. Compelling evidence supports the use of cannabis and CBD in a plethora of pathological conditions, some of which stem from the exacerbation of the inflammatory response of PMN and include pain [36], multiple sclerosis [37], diabetic complications [38], inflammatory bowel disease [39], cardiovascular diseases [40], hypoxia-ischemia injury [41], rheumatoid arthritis [35], cancer [42], and Crohn’s disease [43]. Collectively, our findings point to PMN as potential targets for the therapeutic actions of cannabis and CBD.…”

Section: Discussionmentioning

confidence: 99%

A Novel Standardized Cannabis sativa L. Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte Functions

Tagne

Marino

Legnaro

et al. 2019

IJMS

View full text Add to dashboard Cite

Cannabis and cannabinoids offer significant therapeutic benefits for a wide scope of pathological conditions. Among them, the clinical issues rooted in inflammation stand out, nonetheless, the underlying mechanisms are not yet plainly understood. Circumstantial evidence points to polymorphonuclear leukocytes (PMN) as targets for the anti-inflammatory effects of cannabis. Therefore, we conducted this study to assess the effects of CM5, a novel Cannabis sativa L. extract standardized in 5% cannabidiol (CBD), on human PMN functions, including cell migration, oxidative metabolism and production of tumour necrosis factor (TNF)-α. We then sought to investigate whether such effects could be ascribed to its content in CBD. Cell migration was assessed by the Boyden chamber assay, oxidative metabolism by means of spectrofluorimetric measurement of reactive oxygen species (ROS) production, and TNF-α was measured by real time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Results show that both CM5 and CBD inhibit PMN migration, ROS and TNF-α production, indicating that CBD may be the main item responsible for the effects of CM5. CM5 is however more potent than CBD on cell migration and TNF-α production, and less effective on ROS production, suggesting that beyond CBD, other components of the cannabis plant may contribute to the biological effects of the extract. As a whole, such results support the use of cannabis standardized extract and CBD to stem inflammation; however, they also warrant in-depth investigation of the underlying cellular and molecular mechanisms to better exploit their therapeutic potential.

show abstract

Section: Discussionmentioning

confidence: 99%

A Novel Standardized Cannabis sativa L. Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte Functions

Tagne

Marino

Legnaro

et al. 2019

IJMS

View full text Add to dashboard Cite

show abstract

“…7 Furthermore, we previously reported that IL-18 is secreted from neutrophils using a muscle pain model. 9…”

Section: Introductionmentioning

confidence: 99%

Involvement of inflammasome activation via elevation of uric acid level in nociception in a mouse model of muscle pain

et al. 2019

Self Cite

View full text Add to dashboard Cite

Muscle pain is a common condition in many diseases and is induced by muscle overuse. Muscle overuse induces an increase in uric acid, which stimulates the nucleotide-binding oligomerization domain-like receptor (NLR). This receptor contains the pyrin domain NLRP-3 inflammasome which when activated, results in the secretion of potent pro-inflammatory cytokines such as interleukin-1β (IL-1β). The aim of this study was to investigate the involvement of inflammasome activation via the elevation of uric acid level in nociception in a mouse model of muscle pain. The right hind leg muscles of BALB/c mice were stimulated electrically to induce excessive muscle contraction. The left hind leg muscles were not stimulated as a control. Mechanical withdrawal thresholds, levels of uric acid, IL-1β, and NLRP3, caspase-1 activity, and the number of macrophages were investigated. Furthermore, the effects of xanthine oxidase inhibitors, such as Brilliant Blue G, caspase-1 inhibitor, and clodronate liposome, on pain were investigated. In the stimulated muscles, mechanical withdrawal thresholds decreased, and the levels of uric acid, NLRP3, and IL-1β, caspase-1 activity, and the number of macrophages increased compared to that in the non-stimulated muscles. Administration of the inhibitors attenuated hyperalgesia caused by excessive muscle contraction. These results suggested that IL-1β secretion and NLRP3 inflammasome activation in macrophages produced mechanical hyperalgesia by elevating uric acid level, and xanthine oxidase inhibitors may potentially reduce over-exercised muscle pain.

show abstract

“…For example, the present study demonstrated, for the first time, the involvement of P2X3 receptors in neutrophil migration induced by static contraction. It is well known that neutrophils have a role on different pain conditions [16,17,65,67], including muscle pain [11,30,33,68,69]. Neutrophils invade skeletal muscles and are assumed to produce pro-inflammatory cytokines after exercise-induced muscle damage [70].…”

Section: Discussionmentioning

confidence: 99%

P2X3 receptors contribute to muscle pain induced by static contraction by a mechanism dependent on neutrophil migration

Aquino

Santos

Jorge

et al. 2019

Purinergic Signalling

View full text Add to dashboard Cite

P2X3 receptors are involved with several pain conditions. Muscle pain induced by static contraction has an important socioeconomic impact. Here, we evaluated the involvement of P2X3 receptors on mechanical muscle hyperalgesia and neutrophil migration induced by static contraction in rats. Also, we evaluated whether static contraction would be able to increase muscle levels of TNF-α and IL-1β. Male Wistar rats were pretreated with the selective P2X3 receptor antagonist, A-317491, by intramuscular or intrathecal injection and the static contraction-induced mechanical muscle hyperalgesia was evaluated using the Randall-Selitto test. Neutrophil migration was evaluated by measurement of myeloperoxidase (MPO) kinetic-colorimetric assay and the cytokines TNF-α and IL-1β by enzyme-linked immunosorbent assay. Intramuscular or intrathecal pretreatment with A-317491 prevented static contraction-induced mechanical muscle hyperalgesia. In addition, A-317491 reduced static contraction-induced mechanical muscle hyperalgesia when administered 30 and 60 min of the beginning of static contraction, but not after 30 and 60 min of the end of static contraction. Intramuscular A-317491 also prevented static contraction-induced neutrophil migration. In a period of 24 h, static contraction did not increase muscle levels of TNF-α and IL-1β. These findings demonstrated that mechanical muscle hyperalgesia and neutrophil migration induced by static contraction are modulated by P2X3 receptors expressed on the gastrocnemius muscle and spinal cord dorsal horn. Also, we suggest that P2X3 receptors are important to the development but not to maintenance of muscle hyperalgesia. Therefore, P2X3 receptors can be pointed out as a target to musculoskeletal pain conditions induced by daily or work-related activities.

show abstract

Involvement of neutrophils and interleukin-18 in nociception in a mouse model of muscle pain

Cited by 24 publications

References 50 publications

A Novel Standardized Cannabis sativa L. Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte Functions

A Novel Standardized Cannabis sativa L. Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte Functions

Involvement of inflammasome activation via elevation of uric acid level in nociception in a mouse model of muscle pain

P2X3 receptors contribute to muscle pain induced by static contraction by a mechanism dependent on neutrophil migration

Contact Info

Product

Resources

About