Prolactin and Oxytocin: Future Targets

By: Brooklyn A. Bradley, BS; Medically edited by Dr. Deena Kuruvilla, MD

The pathophysiology of migraine is not yet fully understood. It is well-known that there is the role of inflammatory mediators which are activated by the trigeminovascular system in the brainstem. There are also different chemicals in the brain such as dopamine and serotonin which play a role in changes in the electrical activity of the brain. [1]. Recent research has highlighted the pituitary-derived hormone prolactin and the hypothalamic neuropeptide oxytocin, and their role in migraine. In today’s blog post, we will dive deeper into the relationship between these two hormones and the pathophysiology of migraine.

Prolactin is a polypeptide hormone (chemical messenger), that is secreted (released) from the pituitary gland [2]. This hormone is responsible for lactation, breast development, and ovulation and is released during these times. Prolactin also has a role in metabolism, immune system regulation, and pancreatic development [2]. Oxytocin is a non-peptide hormone produced in the hypothalamus, which is the area of the brain that controls body temperature, hunger, and thirst [3,4]. This hormone also has a role in sexual arousal, trust, attachment, and mother-infant bonding.

Both prolactin and oxytocin operate at peripheral (neuromuscular structures outside skull and spinal column) and central levels (brain and spinal cord); however, prolactin has increased pain processing capabilities, while oxytocin blocks the detection of painful stimuli [1]. For this reason, prolactin and oxytocin are involved in the processing of noxious or harmful stimuli. Research has also shown the role of the hypothalamus as a migraine generator [5]. 

Recently, there have been research efforts focused on prolactin and oxytocin, and their role in migraine. Clinical and preclinical studies reported a pronociceptive (increased pain processing) role of prolactin, which is a sensitizing factor for pain-related areas in the trigeminovascular system. The trigeminovascular system has particular relevance for migraine as it has been shown to be activated during migraine attacks [1]. However, oxytocin seems to have an opposite role in the trigeminal pain system and spinal cord. 

A study compared serum levels of prolactin in female subjects with episodic migraine versus chronic migraine [6]. This study found that prolactin serum levels were higher in women with chronic migraine than those with episodic migraine. However, in another study, lower prolactin serum levels were seen during the acute phase of migraine [7]. In a study of patients with chronic migraine where researchers collected blood every hour for 12 hours to investigate the role of the hypothalamus in chronic migraine, it was reported that nocturnal prolactin peaks were lower in patients with chronic migraine [8]. These studies illustrate a potential link between migraine and prolactin; however, it is not clear why different responses are seen in episodic versus chronic migraine.

Oxytocin has the capacity to diffuse into various brain structures and has local release in the amygdala, which is a structure associated with stress and the reward system [1]. In recent years, oxytocin has been shown to have analgesic and antidepressant effects [9]. There is a major relationship between the trigeminovascular system and the hypothalamus, which both are key to understanding the role of oxytocin in migraine. Studies on menstrual migraine have reported that estrogen regulates oxytocin release, and it is possible that it contributes to the activation of trigeminal nociceptors and thus increases the risk of menstrual migraine [10, 11].  Further, trigeminal oxytocin receptors are a therapeutic target for menstrual migraine.

Research has described the roles of prolactin and oxytocin in explaining sex differences in migraine. However, there are still some unanswered questions and challenges exist to find a treatment targeting oxytocin and prolactin. 

 

References:

  1. Szewczyk AK, Ulutas S, Aktürk T, et al (2023) Prolactin and oxytocin: potential targets for migraine treatment. The Journal of Headache and Pain 24:31. https://doi.org/10.1186/s10194-023-01557-6
  2. Al-Chalabi M, Bass AN, Alsalman I (2023) Physiology, Prolactin. In: StatPearls. StatPearls Publishing, Treasure Island (FL)
  3. Lee H-J, Macbeth AH, Pagani J, Young WS (2009) Oxytocin: the Great Facilitator of Life. Prog Neurobiol 88:127–151. https://doi.org/10.1016/j.pneurobio.2009.04.001
  4. Hypothalamus: NCI Dictionary of Cancer Terms. NIH National Cancer Institute. 2011. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/hypothalamus. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/hypothalamus. Accessed 29 Jun 2023
  5. Schulte LH, May A (2016) The migraine generator revisited: continuous scanning of the migraine cycle over 30 days and three spontaneous attacks. Brain 139:1987–1993. https://doi.org/10.1093/brain/aww097
  6. Alia S, Ali RS, Nafiseh E, Ehsan K (2013) Comparison the Serum Level of Prolactin Among Patients With Chronic and Episodic Migraine. Journal of Neurology Research 3:68–72. https://doi.org/10.4021/jnr.v3i2.189
  7. Masoud SA, Fakharian E (2005) Serum prolactin and migraine. Ann Saudi Med 25:489–491. https://doi.org/10.5144/0256-4947.2005.489
  8. Peres MF, Sanchez del Rio M, Seabra ML, et al (2001) Hypothalamic involvement in chronic migraine. J Neurol Neurosurg Psychiatry 71:747–751. https://doi.org/10.1136/jnnp.71.6.747
  9. Goodin BR, Ness TJ Oxytocin – A Multifunctional Analgesic for Chronic Deep Tissue Pain. Current Pharmaceutical Design 21:906–913
  10. Krause DN, Warfvinge K, Haanes KA, Edvinsson L (2021) Hormonal influences in migraine — interactions of oestrogen, oxytocin and CGRP. Nat Rev Neurol 17:621–633. https://doi.org/10.1038/s41582-021-00544-2
  11. Bharadwaj VN, Porreca F, Cowan RP, et al (2021) A new hypothesis linking oxytocin to menstrual migraine. Headache 61:1051–1059. https://doi.org/10.1111/head.14152
Published On: July 17th, 2023