Existing evidence supports the fact that men and women have different pain perceptions and experiences; however, the underlying mechanism for why these differences exist has been unclear. Frank Porreca, Ph.D., professor of Pharmacology, anesthesiology, cancer biology and neuroscience at the University of Arizona College of Medicine, Tucson in the Department of Pharmacology and colleagues set out to explore why women experience and express greater degrees of pain when compared to their male counterparts, and why women may be disappointed to learn that certain analgesic drugs may not only fail to treat their pain, but actually contribute more to their overall discomfort. 

In a recent interview, Dr. Porreca commented "Of all these female-prevalent pain disorders, migraines are among the most common, with about 35 million migraine patients in the United States, and three out of four of those are women. In addition, in fibromyalgia patients, as many as nine out of 10 are women; for irritable bowel syndrome, three out of four are women. When you add up all those women with pain—if you can normalize that—this would provide a huge and important impact on medical care," said Dr. Porreca.

The researchers explored the role prolactin plays in the overall clinical presentation and the patient’s personal reported experience of pain. The hormone prolactin has numerous functions and is now known to be secreted from sources beyond just the pituitary gland, which was the first known origin of its release. Medication-induced changes in prolactin are recognized to be associated with dopamine fluctuations, notably with dopamine antagonists such as antipsychotic agents, increasing prolactin levels. Conversely, patients with a pituitary  tumor that produces an excessive amount of prolactin hormone, also known as a prolactinoma, can be treated with dopamine agonists to reduce the amount of circulating prolactin. 

According to the team, women have a naturally occurring higher circulating prolactin level than men and also exhibit a greater sensitivity to pain. Further, they extrapolated the impact of yet another drug induced disruption of hormonal function caused by opiates resulting in hyperprolactinemia and galactorrhea, though transient, which occurs more often in women than men. 

The researchers explored mechanisms that they hypothesized as possibly mediating this gender difference in pain processing in order to provide potential novel approaches to pharmacologic treatment. They reported that the expression of prolactin receptor “long” (PRLR-L) and prolactin receptor “short” ( PRLR-S) was much greater in female than in male dorsal root ganglia (DRGs). The scientists hypothesized that expression of these different isoform receptors may change throughout a woman’s life, during “pathologically painful conditions” that can affect their nociceptor sensitivity, allowing them to endure otherwise extremely painful conditions such as childbirth. Ironically, opiate pain medications can influence this same nociceptor sensitization pathway, leading to opioid-induced hyperalgesia and allodynia, a central pain response that results from a normally nonpainful stimulation, such as changes in temperature.  

Examining female mice, the team found that the PRLR-S, but not the long isoform PRLR-L, was responsible for influencing the excitability of sensory neurons in these female rodents. Further, Chen and colleagues wrote that this study examining opioid-induced hyperalgesia (OIH) established that the administration of opioids, not nerve injury caused by trauma, increased prolactin and decreased PRLR-L in female rodents, promoting activation of PRLR-S and subsequent development of OIH. Further, they found that prolactin inhibition prevented the occurrence of OIH in female animals. 

The team concluded that targeting PRL signaling might be an effective therapy for preventing OIH in women.

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