Intrathecal oxytocin for neuropathic pain: A randomized, controlled, cross-over trial

Objective To investigate the effect of intrathecal oxytocin compared to placebo on pain and hypersensitivity in individuals with chronic neuropathic pain. Study design Randomized, controlled, double-blind cross-over study Setting Outpatient clinical research unit. Subjects Individuals between ages of 18 and 70 years with neuropathic pain caudal to the umbilicus for at least 6 months. Methods Individuals received two blinded intrathecal injections of either oxytocin or saline, separated by at least 7 days, and ongoing neuropathic pain (VAS: visual analog scale) and areas of hypersensitivity were measured at intervals for 4 hours. The primary outcome was VAS pain, analyzed by linear mixed effects model. Secondary outcomes were verbal pain intensity scores at intervals for 7 days and areas of hypersensitivity and elicited pain for 4 hr after injections. Results The study was stopped early after completion of 5 of 40 subjects planned due to slow recruitment and funding limitations. Pain intensity prior to injection was 4.75 ± 0.99 and modeled pain intensity decreased more after oxytocin than placebo to 1.61 ± 0.87.and 2.49 ± 0.87, respectively (p=0.003). Daily pain scores were lower in the week following injection of oxytocin than saline (2.53 ± 0.89 vs 3.66 ±0.89; p=0.001). Hypersensitivity differed between oxytocin and placebo by small amounts in opposite directions depending on modality tested. There were no study drug related adverse effects. Discussion Although limited by the small number of subjects studied, oxytocin reduced pain more than placebo in all subjects. Further study of spinal oxytocin in this population is warranted. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT02100956 ### Funding Statement This study was funded by the US National Institutes of Health, grant R37 GM48085 to James C. Eisenach ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval was provided by the Wake Forest Sciences Institutional Review Board on 04/21/2014 (IRB00027272). In addition, intrathecal oxytocin was administered under Investigational New Drug approval from the US Food and Drug Administration (IND 107,166) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors