Oxytocin modulates intrinsic neural activity in patients with chronic low back pain

Abstract

Eur J Pain. 2020;24:945-955. | 945 wileyonlinelibrary.com/journal/ejpThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractBackground: Modulation of pain perception by oxytocin (OXT) has attracted increased scientific and clinical interest. Neural mechanisms underlying these effects are poorly understood. In this study, we aimed to investigate the effects of intranasally applied OXT on intrinsic neural activity in patients with chronic low back pain (cLBP). Methods: Twenty-four male patients with cLBP and 23 healthy males were examined using resting-state functional magnetic resonance imaging. Participants were scanned twice and received either intranasally applied OXT (24 international units) or placebo 40 min before scanning. The fractional amplitude of low-frequency fluctuations (fALFF) was computed to investigate regionally specific effects of OXT on intrinsic neural activity. In addition a multivariate statistical data analysis strategy was employed to explore OXT-effects on functional network strength. Results: Differential effects of OXT were observed in cLBP and healthy controls.FALFF decreased in left nucleus accumbens and right thalamus in cLBP and increased in right thalamus in healthy controls after OXT application compared to placebo. OXT also induced activity changes in bilateral thalamus, left caudate nucleus and right amygdala in cLBP. OXT was associated with increased medial frontal, parietal and occipital functional network strength, though this effect was not group-specific. Regression analyses revealed significant associations between left nucleus accumbens, left caudate nucleus and right amygdala with pain-specific psychometric scores in cLBP. Conclusions: These data suggest OXT-related modulation of regional activity and neural network strength in patients with cLBP and healthy controls. In patients, distinct regions of the pain matrix may be responsive to modulation by OXT. Significance: Our data suggest significant oxytocin-related modulation of intrinsic regional activity and neural network strength in patients with chronic low back pain and healthy controls. In patients, distinct regions of the pain matrix may be responsive to modulation by oxytocin. Therapeutic effects of oxytocin for improved pain treatment need to be further investigated. K E Y W O R D S chronic pain, fALFF, MRI, multivariate analysis, resting state, source-based morphometry SUPPORTING INFORMATION Additional supporting information may be found online in the Supporting Information section. How to cite this article: Schneider I, Schmitgen MM, Boll S, et al. Oxytocin modulates intrinsic neural activity in patients with chronic low back pain. Eur J Pain. 2020;24:945-955. https://doi.

Neural Functions of Hypothalamic Oxytocin and its Regulation

“…This finding suggests that disorders in OT/OTR signaling can cause breast and nipple pain and its associated breastfeeding cessation. By contrast, IAO for 4 weeks can significantly improve chronic pelvic pain in 1/3 women observed ( Flynn et al, 2021 ) and that IAO improves pains in patients with chronic low back pain ( Schneider et al, 2020 ). In rats, neuropathic pain induced by partial sciatic nerve ligation upregulates OT synthesis in the SON and PVN as well as axon terminals of OT neurons in the posterior pituitary and spinal cord ( Nishimura et al, 2019 ).…”

“…In rats, increased release of opiate peptides from the periaqueductal gray area likely mediates OT analgesic effect ( Yang et al, 2011 ). OT analgesic effect on chronic pain is associated with its increases of intrinsic neural activity of the medial frontal, parietal and occipital functional network and the associations between left NAc, left caudate nucleus and right amygdala with pain-specific psychometric scores ( Schneider et al, 2020 ). Moreover, this OT effect involves increased GABAergic transmission at the cortical insular level and activating descending spinal noradrenergic mechanisms ( Gamal-Eltrabily et al, 2020 ).…”

Intranasal Administration for Pain: Oxytocin and Other Polypeptides

“…IN administered oxytocin has been investigated by several groups for relief of migraine and other pain types [ 26 ]. For example, analgesic effects of IN applied oxytocin have also been shown for pain after mild traumatic brain injury [ 54 ], wound pain [ 55 ], chronic low back pain [ 56 ] and chronic pelvic pain [ 57 ]. Modulation of neuronal activity of the trigeminal nerve, limbic and cortical brain regions as well as ascending and descending pain pathways in the spinal cord have been suggested as potential mechanisms for oxytocin’s pain-modulating effects [ 58 ].…”

Links Between the Neurobiology of Oxytocin and Human Musicality

“…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).…”

“…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 ).…”