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Human Studies of Oxytocin for Pain

A literature review by Rash et al.16 identified nine qualifying studies that investigated the relationship between oxytocin and pain in humans. Multiple formulations of oxytocin were used in these studies, including the inhalation of oxytocin vapor, injection, and intranasal oxytocin. Four studies assessed endogenous oxytocin in blood plasma, four studies administered exogenous oxytocin relative to a placebo, and one study assessed the exogenous administration of oxytocin relative to a placebo as well as endogenous oxytocin concentrations in blood plasma. This review found that the effect of oxytocin on pain was generally consistent, suggesting that oxytocin may decrease pain sensitivity. Higher endogenous oxytocin concentrations were associated with lower pain sensitivity in four of five studies that assessed plasma oxytocin. Exogenous oxytocin was effective in reducing pain in three out of five studies. Each study is outlined below:

  • • Yang24 studied intrathecal injection of oxytocin in 155 adult patients with acute and chronic lower back pain compared to 65 adult controls. Oxytocin was shown to relieve acute and chronic lower back pain, and both groups exhibited lower blood plasma oxytocin concentrations compared to pain-free controls.
  • • Alfven25 studied the plasma oxytocin concentration of children with psychosomatic recurrent abdominal pain and children with organic abdominal disease producing pain. Plasma oxytocin (fasting morning sample) was measured by radioimmunoassay in 63 children with abdominal pain or inflammatory bowel disease and compared to a control group of 79 healthy children. Plasma oxytocin concentration was significantly lower in children with abdominal pain and inflammatory bowel disease compared to controls.
  • • Alfven, de la Torre, and Uvnas-Moberg26 investigated the plasma concentrations of oxytocin, cortisol, and prolactin in 40 children with recurrent abdominal pain of non-organic origin compared to 34 controls. A blood sample (fasting morning sample) was collected and oxytocin, cortisol, and prolactin were measured by radioimmunoassay. Oxytocin and cortisol concentrations in the children with abdominal pain were found to be significantly reduced compared with those of the controls. The low oxytocin and cortisol levels persisted at a second examination 3 months later. No significant differences in the prolactin levels were observed between children with abdominal pain and controls.
  • • A double-blind, placebo-controlled pilot study was conducted by Ohlsson27 et al. in 59 women with chronic constipation to examine the effects of long-term treatment with oxytocin. The study consisted of a 2-week baseline period followed by a 13-week treatment period of twice daily nasal oxytocin (40 IU twice daily) or placebo and a 2-week posttreatment follow-up period. Abdominal symptoms were rated daily. A total of 49 women were included in the analysis (23 women randomized to oxytocin, 26 women randomized to placebo). The oxytocin group demonstrated no significant advantage over placebo for constipation. Oxytocin seemed to have a positive effect on abdominal pain and discomfort and depressed mood.
  • • A study by Anderberg and Uvnas-Moberg28 assessed plasma oxytocin levels in 39 women with fibromyalgia with different hormonal status and in depressed and non-depressed patients and compared to 30 controls to relate oxytocin concentrations to adverse symptoms. Blood samples were drawn twice with an interval of 14 days during the 28-day period, and patients recorded symptoms daily. Oxytocin levels did not differ significantly between patients and controls or groups based on hormonal status compared to controls. Patients with high pain, stress, and depression had significantly lower levels of oxytocin when compared to patients who scored low in these symptoms. Low levels of oxytocin were also found in depressed patients with fibromyalgia compared to non-depressed patients.
  • • Uryvaev and Petrov29 studied pain sensitivity after treatment with super low doses of oxytocin. Forty-eight healthy adults participated and received either oxytocin (n = 16), subthreshold oxytocin (n = 16), or placebo (n = 16) by inhalation. A finger prick pain test was performed twice. Finger prick pain was reported as reduced when participants were infused with continuous inhalation of oxytocin (n = 16) relative to the continuous inhalation of placebo (n = 16). Subthreshold oxytocin resulted in no change.
  • • A study by Louvel et al.30 studied the effects of oxytocin on colonic perception of intraluminal distension in 26 patients with irritable bowel syndrome (IBS), using a flaccid bag placed in the descending colon and connected to a computerized barostat. Symptomatic responses (first sensation and pain) were evaluated during isobaric distensions, performed automatically by the barostat, during a continuous infusion of oxytocin at various doses or placebo. Continuous intravenous administration of oxytocin resulted in a dose response decrease in reports of pain.
  • • Singer et al.31 measured the effects of oxytocin on pain processing in a double-blind placebo-controlled study of 20 male participants receiving painful electrical stimulation to their own hand (self-condition). The study consisted of two scheduled sessions approximately 10 days apart. Oxytocin nasal spray or placebo was administered to participants four times with a delay of 45 seconds between administrations at each session. Each administration of oxytocin contained approximately 4 IU, for a total of 32 IU. After each trial of painful stimulation, participants indicated how they felt about the stimulation by rating the degree of unpleasantness/pleasantness on an analogue rating scale. There was no significant difference between the oxytocin and placebo groups on the average unpleasantness ratings.
  • • A study by Grewen et al.32 examined the relationship between plasma oxytocin and pain sensitivity and explored the relation of oxytocin to other factors known to influence pain perception. Forty-eight women (25 African American, 23 non-Hispanic white) participated in the study. Participants underwent three test pain procedures (ischemic, thermal heat, and cold pressor) to assess threshold, tolerance, and subjective intensity and unpleasantness of each type of pain stimulus. Measurements included plasma oxytocin levels measured by radioimmunoassay and depression and anxiety questionnaires. Greater oxytocin levels were correlated with greater tolerance to ischemic pain and cold pressor tolerance but not thermal heat tolerance. African American women demonstrated significantly lower pain tolerance across tasks compared with non-Hispanic Whites and also exhibited lower plasma oxytocin levels.32 This study demonstrated that there may be an ethnic factor involved in oxytocin and pain modulation. More studies are needed to further explore this association.
 
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