A Nonpeptide Oxytocin Receptor Agonist for a Durable Relief of Inflammatory Pain

Hilfiger, Louis; Zhao, Qian; Kerspern, Damien; Inquimbert, Perrine; Andry, Virginie; Goumon, Yannick; Darbon, Pascal; Hibert, Marcel; Charlet, Alexandre

doi:10.1038/s41598-020-59929-w

Cited by 40 publications

(44 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We consider that some of the secreted oxytocin is consumed for pain relief; thus, the salivary oxytocin levels would vary widely. In addition, the metabolism of oxytocin is rapid [ 56 ]. Previous studies showed that the half-life of oxytocin in the blood and cerebrospinal fluid is 5 min and 20 min, respectively [ 57 , 58 ].…”

Section: Discussionmentioning

confidence: 99%

Pain relief associated with decreased oxyhemoglobin level in left dorsolateral prefrontal cortex

et al. 2021

View full text Add to dashboard Cite

Pain in the elbow, shoulder, knee, lower back, and various other joints is relieved by adhesion of pyramidal thorn patches. To elucidate the pain relief mechanism induced by the patches, we established a quantitative method for estimating the pain reduction and investigated the brain regions that change in association with pain relief. We first attempted to quantify the pain relief using transcutaneous electric stimulation (TCES) and a visual analog scale (VAS), and then applied near-infrared spectroscopy (NIRS) to the prefrontal cortex, including the dorsolateral prefrontal cortex (DLPFC) and the orbitofrontal cortex (OFC). We also examined the salivary oxytocin levels, which are thought to reflect oxytocin secretion levels from the posterior pituitary in the brain. Application of pyramidal thorn patches to pain regions decreased the pain degree estimated using TCES and VAS. Oxyhemoglobin levels were likely to be decreased in the left DLPFC on the basis of NIRS measurements during patch treatment, suggesting that the left DLPFC is involved in pain relief. On the other hand, the salivary oxytocin levels varied widely. A potential reason for the varying salivary oxytocin levels is its utilization in the pain region as an analgesic agent. Our results suggest that the left DLPFC will become a target brain region for pain therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Pain relief associated with decreased oxyhemoglobin level in left dorsolateral prefrontal cortex

et al. 2021

View full text Add to dashboard Cite

show abstract

“…This peptide binds to μ-opioid receptors and plays a role in social networking and maintaining social bonds (Pearce et al, 2017 ). These observations are important, but it should be noted that many other factors can influence the perception and processing of pain (Millan, 2002 ), including oxytocin (Gamal-Eltrabily et al, 2020 ; Hilfiger et al, 2020 ; Schneider et al, 2020 ), which as described earlier positively modulates signaling mediated by opioid receptors (dal Monte et al, 2017 ; Meguro et al, 2018 ; Salighedar et al, 2019 ). Furthermore, depending on age and health status, the perception of pain does not necessarily reflect circulating β-endorphin levels (Bruehl et al, 2017 ; Ahn et al, 2019 ).…”

Section: The Links Between Oxytocin and Musicmentioning

confidence: 93%

“…Similarly, the use of intranasal oxytocin as a therapeutic tool in conditions such as PTSD shows promise (Giovanna et al, 2020 ) and may be even more effective when used with other treatments including combination with appropriate prosocial music-related activities. As another example, the combined use of music and the anti-nociceptive properties of oxytocin may enhance the therapeutic efficacy of strategies aimed at reducing the perception of chronic (Garza-Villarreal et al, 2017 ; Hilfiger et al, 2020 ; Schneider et al, 2020 ) or peri-operative pain (Nilsson et al, 2005 , 2009 ; Nilsson, 2009 ; Van der Heijden et al, 2015 ). Last but not least, the use of oxytocin in the treatment of autism spectrum disorders (Yamasue and Domes, 2018 ) and other psychiatric conditions (Peled-Avron et al, 2020 ) may benefit from synergistic application with appropriate music-related therapeutic strategies (Quintin, 2019 ).…”

Section: Conclusion and Therapeutic Implicationsmentioning

confidence: 99%

Links Between the Neurobiology of Oxytocin and Human Musicality

Harvey

2020

Front. Hum. Neurosci.

View full text Add to dashboard Cite

The human species possesses two complementary, yet distinct, universal communication systems—language and music. Functional imaging studies have revealed that some core elements of these two systems are processed in closely related brain regions, but there are also clear differences in brain circuitry that likely underlie differences in functionality. Music affects many aspects of human behavior, especially in encouraging prosocial interactions and promoting trust and cooperation within groups of culturally compatible but not necessarily genetically related individuals. Music, presumably via its impact on the limbic system, is also rewarding and motivating, and music can facilitate aspects of learning and memory. In this review these special characteristics of music are considered in light of recent research on the neuroscience of the peptide oxytocin, a hormone that has both peripheral and central actions, that plays a role in many complex human behaviors, and whose expression has recently been reported to be affected by music-related activities. I will first briefly discuss what is currently known about the peptide’s physiological actions on neurons and its interactions with other neuromodulator systems, then summarize recent advances in our knowledge of the distribution of oxytocin and its receptor (OXTR) in the human brain. Next, the complex links between oxytocin and various social behaviors in humans are considered. First, how endogenous oxytocin levels relate to individual personality traits, and then how exogenous, intranasal application of oxytocin affects behaviors such as trust, empathy, reciprocity, group conformity, anxiety, and overall social decision making under different environmental conditions. It is argued that many of these characteristics of oxytocin biology closely mirror the diverse effects that music has on human cognition and emotion, providing a link to the important role music has played throughout human evolutionary history and helping to explain why music remains a special prosocial human asset. Finally, it is suggested that there is a potential synergy in combining oxytocin- and music-based strategies to improve general health and aid in the treatment of various neurological dysfunctions.

show abstract

“…3;). CFA-model, like others inflammatory-induced pain hypersensitivity models, induces mechanical, thermal heat and cold hyperalgesia, with a plateau in hyperalgesia observed between 24 h and 48 h following the injection 24 .…”

Section: Menthol and Pulegone Induce In Vivo Anti-hyperalgesiamentioning

confidence: 97%

“…We first performed a dose-response curve of the putative analgesic effects of menthol and pulegone, measured on mechanical, thermal heat and thermal cold sensitivities, 40 min after a single intra-peritoneal (i.p) injection that occured 24 h after intra-plantar injection of complete Freund adjuvant 24 (CFA; Fig. 3;).…”

Section: Menthol and Pulegone Induce In Vivo Anti-hyperalgesiamentioning

confidence: 99%

Anti-Inflammatory and Analgesic Properties of Pulegone, a Major Component in Calamintha Nepeta

Charlet

Petitjean²,

Hilfiger

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Monoterpenes are small molecules, composed of two isoprene units, able to pass through the blood brain barrier, allowing to target both peripheral and central pain pathways. They are the main components of essential oils, responsible for their diverse well-known biological activities. Menthol, the main monoterpene found in Mentha piperita (L.) is known to modulate nociceptive threshold and is present in different curative preparations that reduces sensory hypersensitivities in pain conditions. While pulegone is a menthol-like monoterpene, only a limited number of studies focuses on its putative analgesic effects. Pulegone is the most abundant monoterpene presents in Calamintha nepeta (L.), a Laminaceae plant used in traditional medicine to alleviate rheumatic disorders, a chronic inflammatory disease. Here, we compared the impacts of menthol and pulegone on pain and inflammation. First, we described that both monoterpenes are anti-inflammatory compounds. Secondly, we found that while menthol is highly cytotoxic at anti-inflammatory concentrations, the cytotoxic effects of pulegone are limited, if not absent. Finally, in a model of peripheral inflammatory-induced pain a pulegone treatment exerts a significantly higher anti-hyperalgesic effect than menthol in response to mechanical stimuli, heat and cold thermal stimulations than a menthol treatment. In conclusion we demonstrated that pulegone is an anti-inflammatory compound and it is acting a potent pain-killer in acute inflammatory pain condition.

show abstract

A Nonpeptide Oxytocin Receptor Agonist for a Durable Relief of Inflammatory Pain

Cited by 40 publications

References 33 publications

Pain relief associated with decreased oxyhemoglobin level in left dorsolateral prefrontal cortex

Pain relief associated with decreased oxyhemoglobin level in left dorsolateral prefrontal cortex

Links Between the Neurobiology of Oxytocin and Human Musicality

Anti-Inflammatory and Analgesic Properties of Pulegone, a Major Component in Calamintha Nepeta

Contact Info

Product

Resources

About