The Comprehensive Neural Mechanism of Oxytocin in Analgesia

Abstract

: Oxytocin (OXT) is a nine amino acid neuropeptide hormone that has become one of the most intensively studied molecules in the past few decades. The vast majority of OXT is synthesized in the periventricular nucleus and supraoptic nucleus of the hypothalamus, and a few are synthesized in some peripheral organs (such as the uterus, ovaries, adrenal glands, thymus, pancreas, etc.) OXT modulates a series of physiological processes, including lactation, parturition, as well as some social behaviors. In addition, more and more attention has recently been focused on the analgesic effects of oxytocin. It has been reported that OXT can relieve tension and pain without other adverse effects. However, the critical role and detailed mechanism of OXT in analgesia remain unclear. Here, this review aims to summarize the mechanism of OXT in analgesia and some ideas about the mechanism.

The psychophysiology of music-based interventions and the experience of pain

“…The immune regulatory and anti-inflammatory effects may have an impact on pain perception, although in humans there is evidence for altered oxytocin levels in some chronic pain conditions (Goodin et al, 2015;Mekhael et al, 2023). Importantly, oxytocin is now well established to act centrally, both in the spinal cord and brain, to reduce the perception of pain (Yang et al, 2022). These anti-nociceptive actions may be mediated by the oxytocin receptor itself or via interaction with opioid and other neuromodulator systems, but in addition the peptide has calming and anxiolytic effects (Kirsch et al, 2005;Neumann and Slattery, 2016;Herpertz et al, 2019), is often negatively correlated with cortisol, and can reduce stress (Lee et al, 2015;Schladt et al, 2017;Neumann and Landgraf, 2019).…”

“…With regard to nociception, oxytocin influences physiological activity in known pain-related sites in the brain such as PAG, prefrontal and somatosensory cortex, ACC, insula, amygdala, NAc, raphe and hypothalamus (Figure 1) (e.g., Gu and Yu, 2007;Eliava et al, 2016;Boll et al, 2018;Poisbeau et al, 2018;Li et al, 2021;Saito et al, 2021;Nishimura et al, 2022;Yang et al, 2022;Iwasaki et al, 2023;Li et al, 2023a). Receptors are also found in the spinal cord and on a proportion of peripheral sensory neurons in the dorsal root ganglia (DRG) (Condes-Lara et al, 2005;Gong et al, 2015;González-Hernández et al, 2017;Poisbeau et al, 2018;Martinez-Lorenzana et al, 2021;Noguri et al, 2022;Yang et al, 2022;Li Y.-J. et al, 2023;.…”

“…Different frequencies of sound vibration can affect a wide range of neurological and physiological functions, gamma waves (around 40 Hz) having significant effects on various levels of neural plasticity (reviewed in Bartel and Mosabbir, 2021). Music is of course made up of a vast array of sound frequencies and has been shown to have measurable effects on oscillatory activity (Thaut et al, 2005;Fujioka et al, 2015;Kučikienė and Praninskienė, 2018;Yurgil et al, 2020;Lerousseau et al, 2021;Yang et al, 2022;Nandi et al, 2023). Interestingly then, in subjects listening to preferred music, EEG recordings revealed reduced low frequency oscillations associated with lower ratings of pain (Lu et al, 2019), and Gu et al (2020) reported that, compared to happy or neutral music, sad music was the most effective in alleviating pain, associated with altered brain oscillations in beta and gamma bands.…”

Insecure Attachment, Oxytocinergic System and C Tactile Fibers: An Integrative and Translational Pathophysiological Model of Fibromyalgia and Central Sensitization Syndromes

“…It has been demonstrated that OT can exert an anti-nociceptive action together with antiinflammatory and anxiolytic effects, thus improving perception and behavioral response to painful or aversive stimuli [74][75][76][77]. In particular, OT can exert its analgesic effect at both spinal cord level and above spinal cord level as well as in the peripheral nervous system.…”

Altered volume of the amygdala subregions in patients with chronic low back pain

“…The amygdala, a limbic brain region, is essential in managing pain and affects the emotional and cognitive responses to it (11,12). Structural neuroimaging studies have demonstrated alterations in the volume of the amygdala in patients with CLBP, and these changes may be linked to their impaired cognitive-affective and emotional processing abilities, as well as to a more persistent chronic pain condition (6,13,14).…”