The aim of this paper is to present and discuss the findings available in scientific literature in the past 40 years regarding the effect of OXT in chronic pain in humans.

Oxytocin (OXT) is a nonapeptide produced in the supraoptic and paraventricular nuclei in the hypothalamus of mammals ¹. Its etymology comes from ancient greek words ὀξύς oxys "fast" and τόκος tokos "birth". In 1906 British physiologist Sir. Henry H. Dale discovered that concentrate extracted from an oxen's posterior hypophysis promotes uterine contractions in other animals when administered intravenously ^2).

In 1909, William Blair Bell, a British gynecologist, was the first to use Dale's findings in a clinical setting on human subjects. He used a concentrate from infundibular regions of women in labor, facilitating uterine contractions and preventing post-partum hemorrhaging. It also helped in the treatment of constipation in both men and women ². In 1911 the same substance, called "infundibulin", facilitated the production of milk in animals and in humans ².

In the 30s of the last century it was assumed that the hormones that were in the neurohypophysis were synthesized by pituicytes of the infundibular process. American researchers of German origin, Ernst and Berta Scharrer, were the first to point out that hormones were produced in the supra-optic and paraventricular nuclei of the hypothalamus. In 1949 Bargman managed to demonstrate that axons that were projected from these nuclei were responsible for the transport of these substances to the neurohypophysis. He named these projections as the "neurosecretory pathway" ².

Starting the decade of the 50s of the last century, the American chemist Vincent du Vigneaud identified the sequence of nine amino acids of OXT and was the first to synthesize it artificially in 1953, ³ he won the Nobel Prize in chemistry in December 1955 for have achieved the characterization and synthesis of the neuropeptide.

The first studies on pain treatment with OXT in humans date from 1987, when Madrazo et al., Used OXT intrathecally in a woman with mesothelioma, achieving an improvement in pain in 88% after 77 minutes of administration ⁴ Other studies report the use of OXT in this way for low back pain ⁵. OXT has also been administered as an analgesic intranasally ^6,7,9.

In general, the analgesic use of OXT in humans has focused on chronic pain; that is, one whose duration is equal to or greater than three months, is prolonged or persistent ¹⁰, negatively impacts the general health, mood and socioeconomic well-being of the person who develops it and is considered as a disease in itself (eleven).

OXT influences higher brain functions, and although its chemical structure has not changed particularly for more than 700 million years, until now the mechanisms underlying its functions are beginning to be understood ¹¹.

OXT works in groups of specific "OXTergic" cells that are part of what is known as the OXT system. It exerts its mechanism of action through binding with specific OXT receptors ¹². Apparently, this neuropeptide mediates the regulation of emotional processes that are part of the transformation of acute pain to chronic pain ¹² and is present peripherally and centrally in various concentrations, which helps explain the differences in experience painful of human and non-human animals ¹².

Studies on the use of OXT in humans for analgesic purposes date back to 1987. Since then, only seven studies have focused on this effect in people with chronic pain ^{4,5,7,9,13,14,15,16} and between they, only three in the last 5 years ^7,9,16 (Table 1).

Table I 

Recently, Goodin, Ness et al., Conducted a critical review of the literature on recent advances that allow a better understanding of the analgesic properties of OXT and its role in nociception ^6,12. In this review, they dedicate a specific part to show evidence of the analgesic effect of OXT in humans and although they agree that studies are scarce, they conclude that OXT has a modulating potential in the perception of pain, which is supported by randomized controlled trials with controlled placebo ^7,13.

Likewise, these authors indicate that low levels of OXT may be associated with a greater perception of chronic pain as it increases peripheral and central sensitization to pain. They report that the studies are heterogeneous but agree that OXT decreases sensitivity to pain. They also found that, in people with chronic pain, OXT levels are lower compared to healthy subjects ⁶.

Among the limitations reported by Goodin et al., are that some of the studies conducted with humans show results that are not directly comparable because the measurement or administration of OXT differ ¹². Finally, they indicate that it is essential to perform studies that allow determining the differences in OXT concentrations at the peripheral and central level (plasma vs. cerebrospinal fluid), as well as the routes of administration in these two levels that differentially affect pain experiences. in humans They finalize their review of OXT and pain in humans, proposing that the use of intranasal OXT be considered standardized, since several studies have used this presentation ⁶.

Tracy et al. also conducted a review of the literature in which they discuss the effective applications of OXT for pain management in a healthy population and its potential use as a modulator of painful experience. They conclude that OXT seems a promising analgesic but that more empirical evidence is still needed to support its efficacy ⁵.