pain is a very unpleasant experience. Fortunately, acute pain after an injury is usually short-lived. However, unrelieved pain or continuous stimulation of nerves can lead to damage to the central nervous system mechanism and promote chronic pain syndromes, causing patients to suffer. Until now, pain-relieving drugs have come with various side effects. Therefore, effective analgesic therapies are urgently needed.
A large body of literature demonstrates that women are more susceptible to pain than men in terms of frequency, severity, and duration of pain. Although there are consistent differences in physiological pain sensitivity between men and women, the underlying mechanisms remain unknown.
Recently, in a study published in "Brain, Behavior, and Immunity" , a research team led by University College Cork in Ireland revealed for the first time the relationship between baseline gut microbiome composition, gender and physical pain in healthy individuals. Relationship. This study lays the foundation for identifying new biomarkers of somatic pain and developing sex-specific treatments for pain.
The peripheral nervous system (PNS) regulates pain sensory pathways in the process of sensing sensory changes and transmitting them to the brain. The central nervous system processes this information and allows for pain perception. Previously, researchers have observed that the intestinal flora plays a key role in the pain regulation pathway.
To investigate the diversity of gut microbiota and its relationship with electrical pain sensitivity, the researchers recruited 15 healthy male participants and 16 healthy female participants aged 18-35 years (nine of whom were undergoing use hormonal contraceptives). All women had normal menstrual cycles and had not used psychotropic drugs, hormonal therapy (except birth control pills), intestinal, neurological disease, or diabetes in the past three months, and had not been diagnosed with diabetes before testing. Take painkillers 24 hours a day. Participants were told to avoid strenuous exercise and alcohol the day before the experiment and to go to bed on time.
The researchers collected saliva and stool samples from the subjects during the examination, including saliva samples collected within an hour after waking up and stool samples collected within 24 hours before the test.
Clinicians assessed participants' pain threshold (PST) for transcutaneous constant current stimulation and recorded their pain tolerance threshold (PTT) and PST.
After neurophysiological assessment, the researchers collected venous blood samples from participants to quantify soluble cluster of differentiation 12 (sCD14) and lipopolysaccharide-binding protein (LBP) levels. They also measured interleukin -6 (IL -6), IL-1β, IL-8, interferon (IFN-γ) and tumor necrosis factor -α (TNF-α) levels. In addition, they extracted fecal DNA and analyzed short-chain fatty acids (SCFA) in the samples as well as cortisol levels in the saliva samples.
Researchers found no significant differences in pain tolerance threshold (PTT) or pain sensation threshold (PST) between men and women, including those using hormonal contraceptives. But when stratified by contraceptive use, PTT to PST ratios were similar in both contraceptive users and non-users during the early follicular (EF) and mid-luteal (ML, 5-8 days after ovulation) phases. Significantly lower. Nonetheless, the PTT/PST ratio decreased significantly in all women throughout the menstrual cycle.
Next, the researchers determined the relative abundance of and in taxonomic groups. There were no differences in alpha or beta diversity index between men and women (with or without contraceptive use) and across menstrual cycle phases. Notably, the researchers observed significant differences in 10 and 5 taxonomic bacterial groups during the menstrual cycle of contraceptive users and normal menstruating women, respectively.
Specifically, contraceptive use was associated with an increase in the relative abundance of Erysipelatoclostridium bacteria during the late follicular (LF) stage Erysipelatoclostridium but not SCFA; plasma lipopolysaccharide in contraceptive users during LF and ML Binding protein (LBP) levels were higher than in men and non-contraceptors, but there was no difference in sCD14 levels.In addition, no differences were observed in plasma IFN-γ, IL-8, and TNF-α concentrations.
The researchers then analyzed the relationship between gut microbiota and levels of SCFA, LBP, sCD14, as well as pro-inflammatory cytokines and electrical pain threshold, to investigate the relative abundance of bacterial genera associated with other parameters in women and men. . The results showed that there was no significant correlation in men; however, in women during the late follicular (LF) stage, PTT and PST were positively correlated with the bacterial abundance of Megasphaera and Prevotella, respectively. Significant negative correlations were observed between Eggerthella bacteria and sCD14 and between Rothia genus (Rothia) and TNF-α.
In the mid-luteal phase (ML), the researchers observed that Anaerofustis bacteria were positively correlated with increased salivary cortisol levels within 30 minutes after waking up; IL-8 levels were negatively correlated with Lachnospiraceae bacteria of the genus UCG-005 Related. Notably, SCFA, PST, PTT, and some inflammatory markers were significantly associated with women in each dataset. There is a positive correlation between pain threshold (PST) and IL-8 levels in women.
These results indicate that healthy adult females have lower PTT to PST ratios during electrical stimulation than males. Additionally, cortisol levels after waking, physical pain thresholds, and birth control pills were associated with specific bacteria in the gut of women, but not men. The relative abundance of Erysipelatoclostridium bacteria in the guts of birth control pill users may indicate that birth control pill use stimulates the growth of this bacteria.
The study also suggests that hormonal contraceptive use may increase systemic LBP levels through hormone-dependent mechanisms rather than through increased intestinal permeability. Taken together, these data confirm that gut microbiota may determine physiological differences in pain perception between the sexes.
The team says further research will help elucidate how gender interacts with host factors and gut microbiota, and how these relationships modulate somatic pain sensitivity.
paper link:
https://doi.org/10.1016/j.bbi.2022.06.002
