Evaluating the efficacy of oxytocin for pain management: An updated systematic review and meta-analysis of randomized clinical trials and observational studies

References

• Stanford EA, Chambers CT, Biesanz JC, Chen E. The frequency, trajectories and predictors of adolescent recurrent pain: a population-based approach. Pain. 2008;138(1):11–19. doi:10.1016/j.pain.2007.10.032.
   PubMed Web of Science ®Google Scholar
• Schopflocher D, Taenzer P, Jovey R. The prevalence of chronic pain in Canada. Pain Res Manag. 2011;16(6):445–50. doi:10.1155/2011/876306.
   PubMed Web of Science ®Google Scholar
• Hadjistavropoulos T, Marchildon GP, Fine PG, Herr K, Palley HA, Kaasalainen S, Béland F. Transforming long-term care pain management in North America: the policy-clinical interface. Pain Med (Malden, Mass). 2009;10(3):506–20. doi:10.1111/j.1526-4637.2009.00566.x.
   PubMed Web of Science ®Google Scholar
• Collier R. A short history of pain management. CMAJ. 2018;190(1):E26–E7. doi:10.1503/cmaj.109-5523.
   PubMed Web of Science ®Google Scholar
• Finnerup NB, Ropper AH. Nonnarcotic methods of pain management. N Engl J Med. 2019;380(25):2440–48. doi:10.1056/NEJMra1807061.
   PubMed Web of Science ®Google Scholar
• Turk DC, Wilson HD, Cahana A. Treatment of chronic non-cancer pain. Lancet (London, England). 2011;377(9784):2226–35. doi:10.1016/S0140-6736(11)60402-9.
   PubMed Web of Science ®Google Scholar
• Kolodny A, Courtwright DT, Hwang CS, Kreiner P, Eadie JL, Clark TW, Alexander GC. The prescription opioid and heroin crisis: a public health approach to an epidemic of addiction. Annu Rev Public Health. 2015;36:559–74. doi:10.1146/annurev-publhealth-031914-122957.
   PubMed Web of Science ®Google Scholar
• Gomes T, Campbell T, Tadrous M, Mamdani MM, Paterson JM, Juurlink DN. Initial opioid prescription patterns and the risk of ongoing use and adverse outcomes. Pharmacoepidemiol Drug Saf. 2021;30(3):379–89. doi:10.1002/pds.5180.
   PubMed Web of Science ®Google Scholar
• Strike C, Watson TM. Losing the uphill battle? Emergent harm reduction interventions and barriers during the opioid overdose crisis in Canada. Int J Drug Policy. 2019;71:178–82. doi:10.1016/j.drugpo.2019.02.005.
   PubMed Web of Science ®Google Scholar
• Busse JW, Wang L, Kamaleldin M, Craigie S, Riva JJ, Montoya L, Mulla SM, Lopes LC, Vogel N, Chen E, et al. Opioids for chronic noncancer pain: a systematic review and meta-analysis. Jama. 2018;320(23):2448–60. doi:10.1001/jama.2018.18472.
   PubMed Web of Science ®Google Scholar
• Gimpl G, Fahrenholz F. The oxytocin receptor system: structure, function, and regulation. Physiol Rev. 2001;81(2):629–83. doi:10.1152/physrev.2001.81.2.629.
   PubMed Web of Science ®Google Scholar
• Heinrichs M, Baumgartner T, Kirschbaum C, Ehlert U. Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress. Biol Psychiatry. 2003;54(12):1389–98. doi:10.1016/S0006-3223(03)00465-7.
   PubMed Web of Science ®Google Scholar
• Neumann ID. Brain oxytocin: a key regulator of emotional and social behaviours in both females and males. J Neuroendocrinol. 2008;20(6):858–65. doi:10.1111/j.1365-2826.2008.01726.x.
   PubMed Web of Science ®Google Scholar
• Martínez-Lorenzana G, Palma-Tirado L, Cifuentes-Diaz C, González-Hernández A, Condés-Lara M. Ultrastructural evidence for oxytocin and oxytocin receptor at the spinal dorsal horn: mechanism of nociception modulation. Neuroscience. 2021;475:117–26. doi:10.1016/j.neuroscience.2021.09.004.
   PubMed Web of Science ®Google Scholar
• Poisbeau P, Grinevich V, Charlet A. Oxytocin signaling in pain: cellular, circuit, system, and behavioral levels. Curr Top Behav Neurosci. 2018;35:193–211.
   PubMedGoogle Scholar
• Yang J, Liang JY, Li P, Pan YJ, Qiu PY, Zhang J, Hao F, Wang DX. Oxytocin in the periaqueductal gray participates in pain modulation in the rat by influencing endogenous opiate peptides. Peptides. 2011;32(6):1255–61. doi:10.1016/j.peptides.2011.03.007.
   PubMed Web of Science ®Google Scholar
• Condés-Lara M, Martínez-Lorenzana G, Rojas-Piloni G, Rodríguez-Jiménez J. Branched oxytocinergic innervations from the paraventricular hypothalamic nuclei to superficial layers in the spinal cord. Brain Res. 2007;1160:20–29. doi:10.1016/j.brainres.2007.05.031.
   PubMed Web of Science ®Google Scholar
• Rojas-Piloni G, Martínez-Lorenzana G, DelaTorre S, Condés-Lara M. Nociceptive spinothalamic tract and postsynaptic dorsal column neurons are modulated by paraventricular hypothalamic activation. Eur J Neurosci. 2008;28(3):546–58. doi:10.1111/j.1460-9568.2008.06366.x.
   PubMed Web of Science ®Google Scholar
• Jo YH, Stoeckel ME, Freund-Mercier MJ, Schlichter R. Oxytocin modulates glutamatergic synaptic transmission between cultured neonatal spinal cord dorsal horn neurons. J Neurosci: Off J Soc Neurosci. 1998;18(7):2377–86. doi:10.1523/JNEUROSCI.18-07-02377.1998.
   PubMed Web of Science ®Google Scholar
• DeLaTorre S, Rojas-Piloni G, Martínez-Lorenzana G, Rodríguez-Jiménez J, Villanueva L, Condés-Lara M. Paraventricular oxytocinergic hypothalamic prevention or interruption of long-term potentiation in dorsal horn nociceptive neurons: electrophysiological and behavioral evidence. Pain. 2009;144(3):320–28. doi:10.1016/j.pain.2009.05.002.
   PubMed Web of Science ®Google Scholar
• Juif PE, Poisbeau P. Neurohormonal effects of oxytocin and vasopressin receptor agonists on spinal pain processing in male rats. Pain. 2013;154(8):1449–56. doi:10.1016/j.pain.2013.05.003.
   PubMed Web of Science ®Google Scholar
• Eliava M, Melchior M, Knobloch-Bollmann HS, Wahis J, da Silva Gouveia M, Tang Y, Ciobanu AC, Triana Del Rio R, Roth LC, Althammer F, et al. A new population of parvocellular oxytocin neurons controlling magnocellular neuron activity and inflammatory pain processing. Neuron. 2016;89(6):1291–304. doi:10.1016/j.neuron.2016.01.041.
   PubMed Web of Science ®Google Scholar
• Nishimori K, Takayanagi Y, Yoshida M, Kasahara Y, Young LJ, Kawamata M. New aspects of oxytocin receptor function revealed by knockout mice: sociosexual behaviour and control of energy balance. Prog Brain Res. 2008;170:79–90.
   PubMed Web of Science ®Google Scholar
• Goldberg DS, McGee SJ. Pain as a global public health priority. BMC Public Health. 2011;11:770. doi:10.1186/1471-2458-11-770.
   PubMed Web of Science ®Google Scholar
• Tunks ER, Crook J, Weir R. Epidemiology of chronic pain with psychological comorbidity: prevalence, risk, course, and prognosis. Can J Psychiatry. 2008;53(4):224–34. doi:10.1177/070674370805300403.
   PubMed Web of Science ®Google Scholar
• Vinall J, Pavlova M, Asmundson GJ, Rasic N, Noel M. Mental health comorbidities in pediatric chronic pain: a narrative review of epidemiology, models, neurobiological mechanisms and treatment. Children (Basel, Switzerland). 2016;3(4). doi:10.3390/children3040040.
   PubMedGoogle Scholar
• Gureje O, Von Korff M, Simon GE, Gater R. Persistent pain and well-being: a World Health Organization study in primary care. Jama. 1998;280(2):147–51. doi:10.1001/jama.280.2.147.
   PubMed Web of Science ®Google Scholar
• Wahis J, Baudon A, Althammer F, Kerspern D, Goyon S, Hagiwara D, Lefevre A, Barteczko L, Boury-Jamot B, Bellanger B, et al. Astrocytes mediate the effect of oxytocin in the central amygdala on neuronal activity and affective states in rodents. Nat Neurosci. 2021;24(4):529–41. doi:10.1038/s41593-021-00800-0.
   PubMed Web of Science ®Google Scholar
• Rash JA, Aguirre-Camacho A, Campbell TS. Oxytocin and pain: a systematic review and synthesis of findings. Clin J Pain. 2014;30(5):453–62. doi:10.1097/AJP.0b013e31829f57df.
   PubMed Web of Science ®Google Scholar
• Bethlehem RA, van Honk J, Auyeung B, Baron-Cohen S. Oxytocin, brain physiology, and functional connectivity: a review of intranasal oxytocin fMRI studies. Psychoneuroendocrinology. 2013;38(7):962–74. doi:10.1016/j.psyneuen.2012.10.011.
   PubMed Web of Science ®Google Scholar
• Grace SA, Rossell SL, Heinrichs M, Kordsachia C, Labuschagne I. Oxytocin and brain activity in humans: a systematic review and coordinate-based meta-analysis of functional MRI studies. Psychoneuroendocrinology. 2018;96:6–24. doi:10.1016/j.psyneuen.2018.05.031.
   PubMed Web of Science ®Google Scholar
• Ma X, Zhao W, Luo R, Zhou F, Geng Y, Xu L, Gao Z, Zheng X, Becker B, Kendrick KM. Sex- and context-dependent effects of oxytocin on social sharing. NeuroImage. 2018;183:62–72. doi:10.1016/j.neuroimage.2018.08.004.
   PubMed Web of Science ®Google Scholar
• Cochran DM, Fallon D, Hill M, Frazier JA. The role of oxytocin in psychiatric disorders: a review of biological and therapeutic research findings. Harv Rev Psychiatry. 2013;21(5):219–47. doi:10.1097/HRP.0b013e3182a75b7d.
   PubMed Web of Science ®Google Scholar
• Miwa Y, Furuya H, Yanai R, Kasama T, Sanada K. The relationship between the serum oxytocin levels, disease activity, the ADLs and the QOL in patients with rheumatoid arthritis. Intern Med (Tokyo, Japan). 2017;56(23):3167–72. doi:10.2169/internalmedicine.9191-17.
   PubMed Web of Science ®Google Scholar
• Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009;6(7):e1000100. doi:10.1371/journal.pmed.1000100.
   PubMed Web of Science ®Google Scholar
• Treede RD, Rief W, Barke A, Aziz Q, Bennett MI, Benoliel R, Cohen M, Evers S, Finnerup NB, First MB, et al. Chronic pain as a symptom or a disease: the IASP classification of chronic pain for the international classification of diseases (ICD-11). Pain. 2019;160(1):19–27. doi:10.1097/j.pain.0000000000001384.
   PubMed Web of Science ®Google Scholar
• Fayaz A, Croft P, Langford RM, Donaldson LJ, Jones GT. Prevalence of chronic pain in the UK: a systematic review and meta-analysis of population studies. BMJ open. 2016;6(6):e010364. doi:10.1136/bmjopen-2015-010364.
   PubMed Web of Science ®Google Scholar
• King S, Chambers CT, Huguet A, MacNevin RC, McGrath PJ, Parker L, MacDonald AJ. The epidemiology of chronic pain in children and adolescents revisited: a systematic review. Pain. 2011;152(12):2729–38. doi:10.1016/j.pain.2011.07.016.
   PubMed Web of Science ®Google Scholar
• Dworkin RH, Turk DC, Farrar JT, Haythornthwaite JA, Jensen MP, Katz NP, Kerns RD, Stucki G, Allen RR, Bellamy N, et al. Core outcome measures for chronic pain clinical trials: IMMPACT recommendations. Pain. 2005;113(1–2):9–19. doi:10.1016/j.pain.2004.09.012.
   PubMed Web of Science ®Google Scholar
• Novy D, Berry MP, Palmer JL, Mensing C, Willey J, Bruera E. Somatic symptoms in patients with chronic non-cancer-related and cancer-related pain. J Pain Symptom Manage. 2005;29(6):603–12. doi:10.1016/j.jpainsymman.2004.09.005.
   PubMed Web of Science ®Google Scholar
• Simpson KR. Clinicians’ guide to the use of oxytocin for labor induction and augmentation. J Midwifery Women’s Health. 2011;56(3):214–21. doi:10.1111/j.1542-2011.2011.00052.x.
   PubMed Web of Science ®Google Scholar
• Arrowsmith S, Wray S. Oxytocin: its mechanism of action and receptor signalling in the myometrium. J Neuroendocrinol. 2014;26(6):356–69. doi:10.1111/jne.12154.
   PubMed Web of Science ®Google Scholar
• Neumann ID, Maloumby R, Beiderbeck DI, Lukas M, Landgraf R. Increased brain and plasma oxytocin after nasal and peripheral administration in rats and mice. Psychoneuroendocrinology. 2013;38(10):1985–93. doi:10.1016/j.psyneuen.2013.03.003.
   PubMed Web of Science ®Google Scholar
• McGowan J, Sampson M, Salzwedel DM, Cogo E, Foerster V, Lefebvre C. PRESS peer review of electronic search strategies: 2015 guideline statement. J Clin Epidemiol. 2016;75:40–46. doi:10.1016/j.jclinepi.2016.01.021.
   PubMed Web of Science ®Google Scholar
• EndNote Team (2013). EndNote X9. Clarviate, Philelphia, PA.
   Google Scholar
• Covidence systematic review software, Veritas Health Innovation, Melbourne, Australia. Available at www.covidence.org.
   Google Scholar
• Cohen J. A coefficient of agreement for nominal scales. Educ Psychol Meas. 1960;20(1):37–46. doi:10.1177/001316446002000104.
   Web of Science ®Google Scholar
• Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA. The cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ (Clinical Research Ed). 2011;343:d5928. doi:10.1136/bmj.d5928.
   PubMed Web of Science ®Google Scholar
• Gluud LL. Bias in clinical intervention research. Am J Epidemiol. 2006;163(6):493–501. doi:10.1093/aje/kwj069.
   PubMed Web of Science ®Google Scholar
• Sanderson S, Tatt ID, Higgins JP. Tools for assessing quality and susceptibility to bias in observational studies in epidemiology: a systematic review and annotated bibliography. Int J Epidemiol. 2007;36(3):666–76. doi:10.1093/ije/dym018.
   PubMed Web of Science ®Google Scholar
• Wood L, Egger M, Gluud LL, Schulz KF, Jüni P, Altman DG, Gluud C, Martin RM, Wood AJ, Sterne JA. Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta-epidemiological study. BMJ (Clinical Research Ed). 2008;336(7644):601–05. doi:10.1136/bmj.39465.451748.AD.
   PubMed Web of Science ®Google Scholar
• Critical Appraisal Skills Programme. Randomised controlled trial standard checklist. 2019 [accessed 2021 Mar 22]. https://casp-uk.net/casp-tools-checklists/.
   Google Scholar
• Critical Appraisal Skills Programme. Cohort Study Checklist. 2019 [accessed 2021 Mar 22]. https://casp-uk.net/casp-tools-checklists/.
   Google Scholar
• Borenstein M. Chapter 27: comprehensive meta‐analysis software. In: Matthias EJPT, Higgins G, Smith D editors. Systematic reviews in health research: meta‐analysis in context. 3rd. Hoboken (NJ): John Wiley & Sons Ltd; 2022. p. 535–48.
   Google Scholar
• Valentine JC, Pigott TD, Rothstein HR. How many studies do you need? A primer on statistical power for meta-analysis. J Educ Behav Stat. 2010;35(2):215–47. doi:10.3102/1076998609346961.
   Web of Science ®Google Scholar
• Lipsey MW, Wilson DB. Practical meta-analysis. Thousand Oaks (CA): SAGE publications, Inc; 2001.
   Google Scholar
• Borenstein M, Higgins JP, Hedges LV, Rothstein HR. Basics of meta-analysis: i(2) is not an absolute measure of heterogeneity. Res Synth Methods. 2017;8(1):5–18. doi:10.1002/jrsm.1230.
   PubMed Web of Science ®Google Scholar
• Ferguson CJ. An effect size primer: a guide for clinicians and researchers. Prof Psychol Res Pr. 2016;40(5):532–38. doi:10.1037/a0015808.
   Google Scholar
• Ioannidis JP, Patsopoulos NA, Rothstein HR. Reasons or excuses for avoiding meta-analysis in forest plots. BMJ (Clinical Research Ed). 2008;336(7658):1413–15. doi:10.1136/bmj.a117.
   PubMed Web of Science ®Google Scholar
• Campbell M, McKenzie JE, Sowden A, Katikireddi SV, Brennan SE, Ellis S, Hartmann-Boyce J, Ryan R, Shepperd S, Thomas J, et al. Synthesis without meta-analysis (SWiM) in systematic reviews: reporting guideline. BMJ (Clinical Research Ed). 2020;368:l6890. doi:10.1136/bmj.l6890.
   PubMed Web of Science ®Google Scholar
• Alfvén G. Plasma oxytocin in children with recurrent abdominal pain. J Pediatr Gastroenterol Nutr. 2004;38(5):513–17. doi:10.1097/00005176-200405000-00010.
   PubMed Web of Science ®Google Scholar
• Alfvén G, de la Torre B, Uvnäs-Moberg K. Depressed concentrations of oxytocin and cortisol in children with recurrent abdominal pain of non-organic origin. Acta Paediatrica (Oslo, Norway: 1992). 1994;83(10):1076–80. doi:10.1111/j.1651-2227.1994.tb12989.x.
   PubMed Web of Science ®Google Scholar
• Anderberg UM, Uvnäs-Moberg K. Plasma oxytocin levels in female fibromyalgia syndrome patients. Z Rheumatol. 2000;59(6):373–79. doi:10.1007/s003930070045.
   PubMed Web of Science ®Google Scholar
• Bazzichi L, Da Valle Y, Rossi A, Giacomelli C, Sernissi F, Giannaccini G, Betti L, Ciregia F, Giusti L, Scarpellini P, et al. A multidisciplinary approach to study the effects of balneotherapy and mud-bath therapy treatments on fibromyalgia. Clin Exp Rheumatol. 2013;31(6 Suppl 79):S111–20.
   PubMed Web of Science ®Google Scholar
• Boll S, Ueltzhoeffer K, Roth C, Bertsch K, Desch S, Nees F, Grinevich V, Herpertz SC. Pain-modulating effects of oxytocin in patients with chronic low back pain. Neuropharmacology. 2020;171:108105. doi:10.1016/j.neuropharm.2020.108105.
   PubMed Web of Science ®Google Scholar
• Boström A, Scheele D, Stoffel-Wagner B, Hönig F, Chaudhry SR, Muhammad S, Hurlemann R, Krauss JK, Lendvai IS, Chakravarthy KV, et al. Saliva molecular inflammatory profiling in female migraine patients responsive to adjunctive cervical non-invasive vagus nerve stimulation: the MOXY Study. J Transl Med. 2019;17(1):53. doi:10.1186/s12967-019-1801-y.
   PubMedGoogle Scholar
• Clark S, Martin F, McGowan RTS, Smidt J, Anderson R, Wang L, Turpin T, Langenfeld-McCoy N, Bauer B, Mohabbat AB. The impact of a 20-minute animal-assisted activity session on the physiological and emotional states in patients with fibromyalgia. Mayo Clinic Proc. 2020;95(11):2442–61. doi:10.1016/j.mayocp.2020.04.037.
   PubMed Web of Science ®Google Scholar
• Flynn MJ, Campbell TS, Robert M, Nasr-Esfahani M, Rash JA. Intranasal oxytocin as a treatment for chronic pelvic pain: a randomized controlled feasibility study. Int J Gynaecol Obstet. 2021;152(3):425–32. doi:10.1002/ijgo.13441.
   PubMed Web of Science ®Google Scholar
• Louvel D, Delvaux M, Felez A, Fioramonti J, Bueno L, Lazorthes Y, Frexinos J. Oxytocin increases thresholds of colonic visceral perception in patients with irritable bowel syndrome. Gut. 1996;39(5):741–47. doi:10.1136/gut.39.5.741.
   PubMed Web of Science ®Google Scholar
• Mameli S, Pisanu GM, Sardo S, Marchi A, Pili A, Carboni M, Minerba L, Trincas G, Carta MG, Melis MR, et al. Oxytocin nasal spray in fibromyalgic patients. Rheumatol Int. 2014;34(8):1047–52. doi:10.1007/s00296-014-2953-y.
   PubMed Web of Science ®Google Scholar
• Ohlsson B, Truedsson M, Bengtsson M, Torstenson R, Sjölund K, Björnsson ES, Simrèn M. Effects of long-term treatment with oxytocin in chronic constipation; a double blind, placebo-controlled pilot trial. Neurogastroenterol Motil: off J Eur Gastrointest Motil Soc. 2005;17(5):697–704. doi:10.1111/j.1365-2982.2005.00679.x.
   PubMed Web of Science ®Google Scholar
• Tracy LM, Labuschagne I, Georgiou-Karistianis N, Gibson SJ, Giummarra MJ. Sex-specific effects of intranasal oxytocin on thermal pain perception: a randomised, double-blind, placebo-controlled cross-over study. Psychoneuroendocrinology. 2017;83:101–10. doi:10.1016/j.psyneuen.2017.05.028.
   PubMed Web of Science ®Google Scholar
• Wang YL, Yuan Y, Yang J, Wang CH, Pan YJ, Lu L, Wu YQ, Wang DX, Lv LX, Li RR, et al. The interaction between the oxytocin and pain modulation in headache patients. Neuropeptides. 2013;47(2):93–97. doi:10.1016/j.npep.2012.12.003.
   PubMed Web of Science ®Google Scholar
• Yang J. Intrathecal administration of oxytocin induces analgesia in low back pain involving the endogenous opiate peptide system. Spine. 1994;19(8):867–71. doi:10.1097/00007632-199404150-00001.
   PubMed Web of Science ®Google Scholar
• Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.3 (updated February 2022). Cochrane, 2022. Available from www.training.cochrane.org/handbook.
   Google Scholar
• Bowler JO, Bartholomew KJ, Kellar I, Mackintosh B, Hoppitt L, Bayliss AP. Attentional bias modification for acute experimental pain: a randomized controlled trial of retraining early versus later attention on pain severity, threshold and tolerance. Eur J Pain (London, England). 2017;21(1):112–24. doi:10.1002/ejp.908.
   PubMed Web of Science ®Google Scholar
• Ankarali H, Ataoglu S, Ankarali S, Guclu H. Pain threshold, pain severity and sensory effects of pain in fibromyalgia syndrome patients: a new scale study. Bangladesh J Medical Sci. 2018;17(3):342–50. doi:10.3329/bjms.v17i3.36987.
   Web of Science ®Google Scholar
• Rash JA, Campbell TS. Future directions for the investigation of intranasal oxytocin and pain. Rheumatol Int. 2014;34(8):1177–78. doi:10.1007/s00296-014-3070-7.
   PubMed Web of Science ®Google Scholar
• Phillips WJ, Ostrovsky O, Galli RL, Dickey S. Relief of acute migraine headache with intravenous oxytocin: report of two cases. J Pain Palliat Care Pharmacother. 2006;20(3):25–28.
   Google Scholar
• Condés-Lara M, Zayas-González H, Manzano-García A, Córdova-Quiroz E, Granados-Mortera J, García-Cuevas M, Morales-Gómez J, González-Hernández A. Successful pain management with epidural oxytocin. CNS Neurosci Ther. 2016;22(6):532–34. doi:10.1111/cns.12551.
   PubMed Web of Science ®Google Scholar
• Domes G, Lischke A, Berger C, Grossmann A, Hauenstein K, Heinrichs M, Herpertz SC. Effects of intranasal oxytocin on emotional face processing in women. Psychoneuroendocrinology. 2010;35(1):83–93. doi:10.1016/j.psyneuen.2009.06.016.
   PubMed Web of Science ®Google Scholar
• Arletti R, Benelli A, Poggioli R, Luppi P, Menozzi B, Bertolini A. Aged rats are still responsive to the antidepressant and memory-improving effects of oxytocin. Neuropeptides. 1995;29(3):177–82. doi:10.1016/0143-4179(95)90021-7.
   PubMed Web of Science ®Google Scholar
• Uvnäs-Moberg K, Eklund M, Hillegaart V, Ahlenius S. Improved conditioned avoidance learning by oxytocin administration in high-emotional male sprague-dawley rats. Regul Pept. 2000;88(1–3):27–32. doi:10.1016/S0167-0115(99)00112-3.
   PubMedGoogle Scholar
• Muin DA, Wolzt M, Marculescu R, Sheikh Rezaei S, Salama M, Fuchs C, Luger A, Bragagna E, Litschauer B, Bayerle-Eder M. Effect of long-term intranasal oxytocin on sexual dysfunction in premenopausal and postmenopausal women: a randomized trial. Fertil Steril. 2015;104(3):715–23 e4. doi:10.1016/j.fertnstert.2015.06.010.
   PubMed Web of Science ®Google Scholar
• Neumann ID, Slattery DA. Oxytocin in general anxiety and social fear: a translational approach. Biol Psychiatry. 2016;79(3):213–21. doi:10.1016/j.biopsych.2015.06.004.
   PubMed Web of Science ®Google Scholar
• Macdonald K, Feifel D. Helping oxytocin deliver: considerations in the development of oxytocin-based therapeutics for brain disorders. Front Neurosci. 2013;7:35. doi:10.3389/fnins.2013.00035.
   PubMed Web of Science ®Google Scholar
• Feifel D, MacDonald K, McKinney R, Heisserer N, Serrano V. A randomized, placebo-controlled investigation of intranasal oxytocin in patients with anxiety. Neuropsychopharmacology. 2011;36:S324–S449.
   Google Scholar
• Lieberz J, Scheele D, Spengler FB, Matheisen T, Schneider L, Stoffel-Wagner B, Kinfe TM, Hurlemann R. Kinetics of oxytocin effects on amygdala and striatal reactivity vary between women and men. Neuropsychopharmacology. 2020;45(7):1134–40. doi:10.1038/s41386-019-0582-6.
   PubMed Web of Science ®Google Scholar
• McCullough ME, Churchland PS, Mendez AJ. Problems with measuring peripheral oxytocin: can the data on oxytocin and human behavior be trusted? Neurosci Biobehav Rev. 2013;37(8):1485–92. doi:10.1016/j.neubiorev.2013.04.018.
   PubMed Web of Science ®Google Scholar
• Pfeifer AC, Schroeder-Pfeifer P, Schneider E, Schick M, Heinrichs M, Bodenmann G, Ehlert U, Herpertz SC, Läuchli S, Eckstein M, et al. Oxytocin and positive couple interaction affect the perception of wound pain in everyday life. Mol Pain. 2020;16:1744806920918692. doi:10.1177/1744806920918692.
   Web of Science ®Google Scholar
• Zunhammer M, Geis S, Busch V, Eichhammer P, Greenlee MW. Pain modulation by intranasal oxytocin and emotional picture viewing - a randomized double-blind fMRI study. Sci Rep. 2016;6:31606. doi:10.1038/srep31606.
   PubMed Web of Science ®Google Scholar
• Paloyelis Y, Doyle OM, Zelaya FO, Maltezos S, Williams SC, Fotopoulou A, Howard MA, Spatiotemporal A. Profile of in vivo cerebral blood flow changes following intranasal oxytocin in humans. Biol Psychiatry. 2016;79(8):693–705. doi:10.1016/j.biopsych.2014.10.005.
   PubMed Web of Science ®Google Scholar
• Cepeda MS, Africano JM, Polo R, Alcala R, Carr DB. What decline in pain intensity is meaningful to patients with acute pain? Pain. 2003;105(1–2):151–57. doi:10.1016/S0304-3959(03)00176-3.
   PubMed Web of Science ®Google Scholar
• Light KC, Grewen KM, Amico JA, Brownley KA, West SG, Hinderliter AL, Girdler SS. Oxytocinergic activity is linked to lower blood pressure and vascular resistance during stress in postmenopausal women on estrogen replacement. Horm Behav. 2005;47(5):540–48. doi:10.1016/j.yhbeh.2004.12.010.
   PubMed Web of Science ®Google Scholar
• Engel S, Klusmann H, Ditzen B, Knaevelsrud C, Schumacher S. Menstrual cycle-related fluctuations in oxytocin concentrations: a systematic review and meta-analysis. Front Neuroendocrinol. 2019;52:144–55.
   PubMed Web of Science ®Google Scholar
• Kirsch P, Esslinger C, Chen Q, Mier D, Lis S, Siddhanti S, Gruppe H, Mattay VS, Gallhofer B, Meyer-Lindenberg A. Oxytocin modulates neural circuitry for social cognition and fear in humans. J Neurosci: Off J Soc Neurosci. 2005;25(49):11489–93. doi:10.1523/JNEUROSCI.3984-05.2005.
   PubMed Web of Science ®Google Scholar
• Valstad M, Alvares GA, Egknud M, Matziorinis AM, Andreassen OA, Westlye LT, Quintana DS. The correlation between central and peripheral oxytocin concentrations: a systematic review and meta-analysis. Neurosci Biobehav Rev. 2017;78:117–24. doi:10.1016/j.neubiorev.2017.04.017.
   PubMed Web of Science ®Google Scholar
• MacLean EL, Wilson SR, Martin WL, Davis JM, Nazarloo HP, Carter CS. Challenges for measuring oxytocin: the blind men and the elephant? Psychoneuroendocrinology. 2019;107:225–31. doi:10.1016/j.psyneuen.2019.05.018.
   PubMed Web of Science ®Google Scholar
• Shea BJ, Reeves BC, Wells G, Thuku M, Hamel C, Moran J, Moher D, Tugwell P, Welch V, Kristjansson E, et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ (Clinical Research Ed). 2017;358:j4008. doi:10.1136/bmj.j4008.
   PubMed Web of Science ®Google Scholar
• You DS, Haney R, Albu S, Meagher MW. Generalized pain sensitization and endogenous oxytocin in individuals with symptoms of migraine: a cross-sectional study. Headache. 2018;58(1):62–77. doi:10.1111/head.13213.
   PubMed Web of Science ®Google Scholar
• Tzabazis A, Kori S, Mechanic J, Miller J, Pascual C, Manering N, Carson D, Klukinov M, Spierings E, Jacobs D, et al. Oxytocin and migraine headache. Headache. 2017;57(Suppl 2):64–75. doi:10.1111/head.13082.
   PubMedGoogle Scholar
• Goadsby PJ, Holland PR, Martins-Oliveira M, Hoffmann J, Schankin C, Akerman S. Pathophysiology of migraine: a disorder of sensory processing. Physiol Rev. 2017;97(2):553–622. doi:10.1152/physrev.00034.2015.
   PubMed Web of Science ®Google Scholar
• Soeken KL, Sripusanapan A. Assessing publication bias in meta-analysis. Nurs Res. 2003;52(1):57–60. doi:10.1097/00006199-200301000-00009.
   PubMed Web of Science ®Google Scholar
• Rash JA, Campbell TS, Cooper L, Flusk D, MacInnes A, Nasr-Esfahani M, Mekhael AA, Poulin PA, Robert M, Yi Y. Evaluating the efficacy of intranasal oxytocin on pain and function among individuals who experience chronic pain: a protocol for a multisite, placebo-controlled, blinded, sequential, within-subjects crossover trial. BMJ open. 2021;11(9):e055039. doi:10.1136/bmjopen-2021-055039.
   PubMed Web of Science ®Google Scholar