Phase 1 Safety Assessment of Intrathecal Oxytocin
Open accessAbstract
AbstractAbstract: Subarachnoid injections of oxytocin did not produce any major adverse events or complications. In a limited protocol for testing analgesia, no analgesic effects were apparent. Background: Preclinical data suggest that oxytocin reduces hypersensitivity by actions in the spinal cord, but whether it produces antinociception to acute stimuli is unclear. In this article, the authors examined the safety of intrathecal oxytocin and screened its effects on acute noxious stimuli. Methods: After institutional review board and Food and Drug Administration approval, healthy adult volunteers received 5, 15, 50, or 150 μg intrathecal oxytocin in a dose-escalating manner in cohorts of five subjects. Hemodynamic and neurologic assessments were performed for 4 h after injections and 24 h later, at which time serum sodium was also measured. Cerebrospinal fluid was obtained 60 min after injection, and responses to noxious heat stimuli in arm and leg as well as temporal summation to repeated application of a von Frey filament were obtained. Results: One subject receiving the highest dose experienced transient hypotension and bradycardia as well as subjective numbness in a lumbo-sacral distribution. No other subject experienced subjective or objective neurologic symptoms. Overall, blood pressure and heart rate increased 1 to 4 h after injection by less than 15% with no dose dependency. There was no effect on serum sodium, and cerebrospinal fluid oxytocin increased in a dose-dependent manner after injection. Pain scores to noxious heat stimuli were unaffected by oxytocin, and the temporal summation protocol failed to show summation before or after drug treatment. Conclusion: This small study supports further investigation on oxytocin for analgesia for hypersensitivity states, with continued systematic surveillance for possible effects on blood pressure, heart rate, and neurologic function. (A nesthesiology 2015; 122:407-13)
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Experimental studies on healthy volunteers using acute noxious electrical, contact heat and cold-pressor stimuli have produced conflicting results on oxytocin antinociception.
“Experimental studies on healthy volunteers using acute noxious electrical, contact heat and cold‐pressor stimuli have produced further conflicting results.”
From The Analgesic Effect of Oxytocin in Humans: A Double‐Blind, Placebo‐Controlled Cross‐Over Study Using Laser‐Evoked Potentials (2016) · cites this paper as [26]
Most reports have not demonstrated any specific antinociceptive properties for oxytocin.
“Most reports have not demonstrated any specific antinociceptive properties for oxytocin 23, 24, 25, including a phase 1 open‐label trial using intrathecal administration 26.”
From The Analgesic Effect of Oxytocin in Humans: A Double‐Blind, Placebo‐Controlled Cross‐Over Study Using Laser‐Evoked Potentials (2016) · cites this paper as [26]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Rolke, R., Baron, R., Maier, C., Tölle, T. R., Treede, R., Beyer, A., Binder, A., Birbaumer, N., Birklein, F., Bötefür, I. C., et al. (2006) · Pain · doi:10.1016/j.pain.2006.01.041 · Cited by 2,606 · see citing works
A review of safety, side-effects and subjective reactions to intranasal oxytocin in human research
MacDonald, E., Dadds, M. R., Brennan, J. L., Williams, K., Levy, F., & Cauchi, A. J. (2011) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.02.015 · Cited by 352 · see citing works
Phase I Safety Assessment of Intrathecal Neostigmine Methylsulfate in Humans
Hood, D. D., Eisenach, J. C., & Tuttle, R. (1995) · Anesthesiology · doi:10.1097/00000542-199502000-00003 · Cited by 282 · see citing works
Self-citationImmunohistochemical localization of oxytocin receptors in human brain
Boccia, M. L., Petrusz, P., Suzuki, K., Marson, L., & Pedersen, C. A. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.08.048 · Cited by 276 · see citing works
Oxytocin-Induced Analgesia and Scratching Are Mediated by the Vasopressin-1A Receptor in the Mouse
Schorscher-Petcu, A., Sotocinal, S., Ciura, S., Dupre, A., Ritchie, J., Sorge, R. E., Crawley, J. N., Hu, S.-B., Nishimori, K., Young, L. J., et al. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.1594-10.2010 · Cited by 189 · see citing works
Breton, J.-D., Veinante, P., Uhl-Bronner, S., Vergnano, A. M., Freund-Mercier, M. J., Schlichter, R., & Poisbeau, P. (2008) · Molecular Pain · doi:10.1186/1744-8069-4-19 · Cited by 152 · see citing works
Oxytocin mediates stress‐induced analgesia in adult mice
Robinson, D. A., Wei, F., Wang, G. D., Li, P., Kim, S. J., Vogt, S. K., Muglia, L. J., & Zhuo, M. (2002) · The Journal of Physiology · doi:10.1113/jphysiol.2001.013492 · Cited by 148 · see citing works
Pharmacokinetic Aspects of Intrathecal Morphine Analgesia
Nordberg, G. F., Hedner, T., Mellstrand, T., & Dahlström, B. E. (1984) · Anesthesiology · doi:10.1097/00000542-198405000-00010 · Cited by 140 · see citing works
Miranda-Cardenas, Y., Rojas‐Piloni, G., Martı́nez-Lorenzana, G., Rodríguez-Jiménez, J., López-Hidalgo, M. A., Freund‐Mercier, M. J., & Condés‐Lara, M. (2006) · Pain · doi:10.1016/j.pain.2006.01.029 · Cited by 131 · see citing works
Eisenach, J. C., Hood, D. D., & Curry, R. S. (1998) · Anesthesia & Analgesia · doi:10.1213/00000539-199809000-00018 · Cited by 122 · see citing works
Self-citationChanges in Blood Pressure and Cardiac Output during Cesarean Delivery
Rosseland, L. A., Hauge, T. H., Grindheim, G., Stubhaug, A., & Langesæter, E. (2013) · Anesthesiology · doi:10.1097/aln.0b013e31829416dd · Cited by 120 · see citing works
Effect of Oxytocin on Placebo Analgesia: A Randomized Study
Kessner, S., Sprenger, C., Wrobel, N., Wiech, K., & Bingel, U. (2013) · JAMA · doi:10.1001/jama.2013.277446 · Cited by 114 · see citing works
Central oxytocin enhances antinociception in the rat
Yang, J., Yang, Y., Chen, J.-M., Liu, W., Wang, C., & Lin, B.-C. (2007) · Peptides · doi:10.1016/j.peptides.2007.03.003 · Cited by 102 · see citing works
Madrazo, I., Franco-Bourland, R. E., León-Meza, V. M., & Mena, I. X. (1987) · Stereotactic and Functional Neurosurgery · doi:10.1159/000100753 · Cited by 98 · see citing works
Involvement of oxytocin in spinal antinociception in rats with inflammation
Yu, S.-Q., Lundeberg, T., & Yu, L. (2003) · Brain Research · doi:10.1016/s0006-8993(03)03019-1 · Cited by 98 · see citing works
Reversal of Peripheral Nerve Injury-induced Hypersensitivity in the Postpartum Period
Gutierrez, S., Liu, B., Hayashida, K., Houle, T. T., & Eisenach, J. C. (2012) · Anesthesiology · doi:10.1097/aln.0b013e318278cd21 · Cited by 75 · see citing works
Self-citationCondés‐Lara, M., Maie, I. A. S., & Dickenson, A. H. (2005) · Brain Research · doi:10.1016/j.brainres.2005.03.020 · Cited by 71 · see citing works
Rojas-Piloni, G., López-Hidalgo, M., Martínez-Lorenzana, G., Rodríguez-Jiménez, J., & Condés-Lara, M. (2007) · Brain Research · doi:10.1016/j.brainres.2006.12.045 · Cited by 67 · see citing works
Preclinical Toxicity Screening of Intrathecal Oxytocin in Rats and Dogs
Yaksh, T. L., Hobo, S., Peters, C. M., Osborn, K. G., Richter, P. J., Rossi, S. S., Grafe, M. R., & Eisenach, J. C. (2014) · Anesthesiology · doi:10.1097/aln.0000000000000148 · Cited by 63 · see citing works
Self-citationQT interval prolongation after oxytocin bolus during surgical induced abortion
Charbit, B., Funck‐Brentano, C., Samain, E., JANNIERGUILLOU, V., Albaladejo, P., & Marty, J. (2004) · Clinical Pharmacology & Therapeutics · doi:10.1016/j.clpt.2004.06.005 · Cited by 56 · see citing works
Eisenach, J. C., Hood, D. D., & Curry, R. S. (1998) · Anesthesia & Analgesia · doi:10.1097/00000539-199809000-00018 · Cited by 48 · see citing works
Self-citationThe puerperium alters spinal cord plasticity following peripheral nerve injury
Gutierrez, S., Hayashida, K., & Eisenach, J. C. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.10.039 · Cited by 25 · see citing works
Self-citationEffects of epinephrine and clonidine on plasma concentrations of spinal bupivacaine
Boico, O., Bonnet, F. J., & Mazoit, J. X. (1992) · Acta Anaesthesiologica Scandinavica · doi:10.1111/j.1399-6576.1992.tb03544.x · Cited by 23 · see citing works
Seifer, D. B., Sandberg, E. C., Ueland, K., & Sladen, R. N. (1985) · PubMed · Cited by 20 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Oxytocin and Pain Perception: From Animal Models to Human Research
Boll, S., de Minas, A. C. A., Raftogianni, A., Herpertz, S. C., & Grinevich, V. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2017.09.041 · Cited by 137 · see citing works
Paloyelis, Y., Krahé, C., Maltezos, S., Williams, S. C., Howard, M. A., & Fotopoulou, A. (2016) · Journal of Neuroendocrinology · doi:10.1111/jne.12347 · Cited by 61 · see citing works
Oxytocin, GABA, and TRPV1, the Analgesic Triad?
González‐Hernández, A., & Charlet, A. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00398 · Cited by 32 · see citing works
Successful Pain Management with Epidural Oxytocin
Condés‐Lara, M., Zayas‐González, H., Manzano‐García, A., Córdova‐Quiroz, E., Granados‐Mortera, J. C., García‐Cuevas, M. A., Morales‐Gómez, J., & González‐Hernández, A. (2016) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12551 · Cited by 29 · see citing works
Chow, L., Chen, Y.-H., Lai, C., Lin, T.-Y., Chen, Y., Kao, J., & Huang, E. Y. (2018) · Anesthesia & Analgesia · doi:10.1213/ane.0000000000002795 · Cited by 28 · see citing works
Boada, M. D., Gutierrez, S., & Eisenach, J. C. (2019) · Pain · doi:10.1097/j.pain.0000000000001495 · Cited by 19 · see citing works
Self-citationSchuh‐Hofer, S., Eichhorn, N., Grinevich, V., & Treede, R. (2018) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2018.00161 · Cited by 16 · see citing works
Severino, A. L., Chen, R., Hayashida, K., Aschenbrenner, C. A., Sun, H., Peters, C. M., Gutierrez, S., Pan, B., & Eisenach, J. C. (2018) · Anesthesiology · doi:10.1097/aln.0000000000002290 · Cited by 17 · see citing works
Self-citationPituitary Hormones and Orofacial Pain
Dussor, G. O., Boyd, J. T., & Akopian, A. N. (2018) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2018.00042 · Cited by 15 · see citing works
González‐Hernández, A., Condés‐Lara, M., García-Boll, E., & Villalón, C. M. (2021) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2021.1856366 · Cited by 12 · see citing works
Manresa, J. A. B., Schliessbach, J., Vuilleumier, P. H., Müller, M., Mußhoff, F., Stamer, U. M., Stüber, F., Arendt‐Nielsen, L., & Curatolo, M. (2021) · European Journal of Pain · doi:10.1002/ejp.1781 · Cited by 11 · see citing works
Randomized controlled trial of intrathecal oxytocin on speed of recovery after hip arthroplasty
Eisenach, J. C., Shields, J. S., Weller, R. S., Curry, R. S., Langfitt, M. K., Henshaw, D. S., Pollock, D. C., Edwards, C. J., Collaborators, S. O. H. S., & Houle, T. T. (2022) · Pain · doi:10.1097/j.pain.0000000000002810 · Cited by 8 · see citing works
Self-citationWirkung von Oxytocin auf das menschliche Schmerzerleben
Pfeifer, A.-C., Ditzen, B., Neubauer, E., & Schiltenwolf, M. (2016) · Der Schmerz · doi:10.1007/s00482-016-0164-z · Cited by 7 · see citing works
Usami, N., Maegawa, H., Hayashi, M., Kudo, C., & Niwa, H. (2024) · PLoS ONE · doi:10.1371/journal.pone.0300081 · Cited by 6 · see citing works
Eisenach, J. C., Curry, R. S., & Houle, T. T. (2023) · Pain Medicine · doi:10.1093/pm/pnad051 · Cited by 5 · see citing works
Self-citationWolfe, M., Wisniewska, H., Tariga, H., Ibanez, G., Collins, J. C., Wiśniewski, K., Qi, S., Srinivasan, K., Hargrove, D. M., & Lindstrom, B. (2018) · Neuropeptides · doi:10.1016/j.npep.2018.05.007 · Cited by 5 · see citing works
Inadvertent Administration of Oxytocin via Epidural
Tcherepanova, A., Achu-Lopes, R. A., O’Grady, N., Vincent, W. R., Sarg, M. T., & Brook, K. (2026) · Hospital Pharmacy · doi:10.1177/00185787251408703 · Cited by 2 · see citing works
Evolution of the Spinal Delivery of Opiate Analgesics
Dhar, D., Poree, L. R., & Yaksh, T. L. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-805353-9.00065-6 · Cited by 2 · see citing works
Guyo, F. B. (2009) · OhioLink ETD Center (Ohio Library and Information Network) · Cited by 2 · see citing works
Review of Neuraxial Agents Producing Analgesia
Dias, E. V., Sorkin, L. S., & Yaksh, T. L. (2023) · Springer eBooks · doi:10.1007/978-3-031-39558-1_21 · Cited by 1 · see citing works
Exploring Nonopioid Analgesic Agents for Intrathecal Use
Hong, J. K.-S., & Rauck, R. L. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-805353-9.00068-1
Zappaterra, M., & Nanda, U. (2020) · Elsevier eBooks · doi:10.1016/b978-0-323-72216-2.00018-1
The oxytocinergic descending control of pain and its modulation by neonatal maternal separation
Melchior, M. (2018) · theses.fr (ABES) · doi:10.70675/368c73c0ze731z4b57zb52cz8f31049fb33c
Circuits neuronaux sous-tendant la régulation émotionnelle par le système ocytocinergique
Goyon, S. (2018) · theses.fr (ABES) · doi:10.70675/c8c9bec0z7b79z4826z862az93b128e1ada6
Analgesic effect of oxytocin and its effectiveness in acute pain management: A systematic review
Mouaddib, H. E., Nguidi, J., Oukfi, B., Bahousse, F.-E., & Ougjij, A. A. (2026) · Medicina de Familia SEMERGEN · doi:10.1016/j.semerg.2026.102788
- Authors
- Eisenach, J. C., Tong, C., & Curry, R.
- Affiliations
- Wake Forest University Health Sciences (US)
- Corresponding author
- Eisenach, James C.
- ORCID
- Eisenach, James C.
- Venue
- Anesthesiology
- Published
- 2015-02
- Volume
- 122
- Issue
- 2
- Pages
- 407-413
- ISSN
- 0003-3022 (ISSN-L)
- PMC
- PMC5242190
- OpenAlex
- W2113714485
- Cited by
- 25
- References
- 23
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 10 · 2017: 1 · 2016: 2 · 2015: 1
- FWCI
- 0.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Anesthesiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R37 GM48805, R37GM048085)
- National Center for Research Resources (M01RR007122)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Surgery › Anesthesia and Pain Management
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
- Keywords
- drug safety, dose escalation, hypersensitivity, antinociception, temporal summation, serum sodium, spinal cord, analgesia
- MeSH terms
- Adult, Dose-Response Relationship, Drug, Female, Follow-Up Studies, Hot Temperature, Humans, Injections, Spinal, Male, Middle Aged, Oxytocin, Pain Measurement, Physical Stimulation, Analgesics, Non-Narcotic, Patient Safety
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
