Low Serum Oxytocin Concentrations Are Associated with Painful Menstruation.

Oxytocin-dependent mechanisms are hypothesized to contribute to painful menses, but clinical trials of oxytocin antagonists for dysmenorrhea have had divergent outcomes. In contrast, broader studies have shown that increased systemic oxytocin concentrations are associated with increased pain tolerance and improved psychosocial function. We sought to confirm whether increased serum oxytocin concentrations are associated with menstrual pain and other psychosocial factors. Women with a history of primary dysmenorrhea (n = 19), secondary dysmenorrhea (n = 12), and healthy controls (n = 15) completed pain and psychosocial questionnaires, provided a medical history, and rated their pain during the first 48 h of menses. Serum samples were collected during menses to measure oxytocin concentrations. Oxytocin was significantly lower in participants with a history of primary (704 ± 33 pg/mL; p < 0.001) or secondary (711 ± 66 pg/mL; p < 0.01) dysmenorrhea compared to healthy controls (967 ± 53 pg/mL). Menstrual pain over the past 3 months (r = -0.58; p < 0.001) and during the study visit (r = -0.45; p = 0.002) was negatively correlated with oxytocin concentrations. Pain catastrophizing (r = -0.39), pain behavior (r = -0.32), and pain interference (r = -0.31) were also negatively correlated with oxytocin levels (p's < 0.05). Oxytocin was not significantly correlated with psychosocial factors. Contrary to our hypothesis, women with a history of primary or secondary dysmenorrhea had lower oxytocin concentrations during menses when compared to healthy controls. Lower circulating oxytocin concentrations were also associated with worse menstrual pain and pain-related behavior. When considering the existing literature, low circulating oxytocin may be a sign of dysfunctional endogenous pain modulation.

Persistent autonomic dysfunction and bladder sensitivity in primary dysmenorrhea.

Menstrual pain, also known as dysmenorrhea, is a leading risk factor for bladder pain syndrome (BPS). A better understanding of the mechanisms that predispose dysmenorrheic women to BPS is needed to develop prophylactic strategies. Abnormal autonomic regulation, a key factor implicated in BPS and chronic pain, has not been adequately characterized in women with dysmenorrhea. Thus, we examined heart rate variability (HRV) in healthy (n = 34), dysmenorrheic (n = 103), and BPS participants (n = 23) in their luteal phase across a bladder-filling task. Both dysmenorrheic and BPS participants reported increased bladder pain sensitivity when compared to controls (p's < 0.001). Similarly, dysmenorrheic and BPS participants had increased heart rate (p's < 0.01), increased diastolic blood pressure (p's < 0.01), and reduced HRV (p's < 0.05) when compared to controls. Dysmenorrheic participants also exhibited little change in heart rate between maximum bladder capacity and after micturition when compared to controls (p = 0.013). Our findings demonstrate menstrual pain's association with abnormal autonomic activity and bladder sensitivity, even two weeks after menses. Our findings of autonomic dysfunction in both early episodic and chronic visceral pain states points to an urgent need to elucidate the development of such imbalance, perhaps beginning in adolescence.

Abdominal skeletal muscle activity precedes spontaneous menstrual cramping pain in primary dysmenorrhea.

BACKGROUND: Dysmenorrhea is a pervasive pain condition that affects 20-50% of reproductive-aged women. Distension of a visceral organ, such as the uterus, could elicit a visceromotor reflex, resulting in involuntary skeletal muscle activity and referred pain. Although referred abdominal pain mechanisms can contribute to visceral pain, the role of abdominal muscle activity has not yet been investigated within the context of menstrual pain. OBJECTIVE: The goal of this study was to determine whether involuntary abdominal muscle activity precedes spontaneous episodes of menstrual cramping pain in dysmenorrheic women and whether naproxen administration affects abdominal muscle activity. STUDY DESIGN: Abdominal electromyography activity was recorded from women with severe dysmenorrhea (n = 38) and healthy controls (n = 10) during menses. Simultaneously, pain was measured in real time using a squeeze bulb or visual analog rheostat. Ninety minutes after naproxen administration, abdominal electromyography activity and menstrual pain were reassessed. As an additional control, women were also recorded off menses, and data were analyzed in relation to random bulb squeezes. Because it is unknown whether mechanisms of menstrual cramps are different in primary or secondary dysmenorrhea/chronic pelvic pain, the relationship between medical history and abdominal muscle activity was examined. To further examine differences in nociceptive mechanisms, pressure pain thresholds were also measured to evaluate changes in widespread pain sensitivity. RESULTS: Abdominal muscle activity related to random-bulb squeezing was rarely observed in healthy controls on menses (0.9 ± 0.6 episodes/hour) and in dysmenorrhea participants off menses (2.3 ± 0.6 episodes/hour). In dysmenorrheic participants during menses, abdominal muscle activity frequently preceded bulb squeezing indicative of menstrual cramping pain (10.8 ± 3.0 episodes/hour; P < .004). Whereas 45% of the women with dysmenorrhea (17 of 38) had episodes of abdominal muscle activity associated pain, only 13% (5 of 38) had episodes after naproxen (P = .011). Women with the abdominal muscle activity-associated pain were less likely to have a diagnosis for secondary dysmenorrhea or chronic pelvic pain (2 of 17) than women without this pain phenotype (10 of 21; P = .034). Similarly, women with the abdominal muscle activity-associated pain phenotype had less nonmenstrual pain days per month (0.6 ± 0.5) than women without the phenotype (12.4 ± 0.3; P = .002). Women with abdominal muscle activity-associated pain had pressure pain thresholds (22.4 ± 3.0 N) comparable with healthy controls (22.2 ± 3.0 N; P = .967). In contrast, women without abdominal muscle activity-associated pain had lower pressure pain thresholds (16.1 ± 1.9 N; P = .039). CONCLUSION: Abdominal muscle activity may contribute to cramping pain in primary dysmenorrhea but is resolvable with naproxen. Dysmenorrheic patients without cramp-associated abdominal muscle activity exhibit widespread pain sensitivity (lower pressure pain thresholds) and are more likely to also have a chronic pain diagnosis, suggesting their cramps are linked to changes in central pain processes. This preliminary study suggests new tools to phenotype menstrual pain and supports the hypothesis that multiple distinct mechanisms may contribute to dysmenorrhea.

Identification of experimental bladder sensitivity among dysmenorrhea sufferers.

BACKGROUND: Dysmenorrhea is a common risk factor for chronic pain conditions including bladder pain syndrome. Few studies have formally evaluated asymptomatic bladder pain sensitivity in dysmenorrhea, and whether this largely reflects excess pelvic symptom reporting due to comorbid psychological dysfunction. OBJECTIVE: We sought to determine whether bladder hypersensitivity is more common among women reporting moderate or greater dysmenorrhea, without chronic pain elsewhere, after accounting for anxiety and depression. Demonstrating this would suggest that dysmenorrhea might be an early clue for visceral or widespread pain hypersensitivity and improve understanding of potential precursors to bladder pain syndrome. STUDY DESIGN: We compared cohorts of regularly menstruating women, without symptoms of chronic pain elsewhere, reporting (1) moderate-to-severe dysmenorrhea (n = 98) and (2) low levels or no menstrual pain (n = 35). Participants underwent rapid bladder filling following a standard water ingestion protocol, serially rating bladder pain and relative urgency during subsequent distension. Potential differences in bladder volumes were controlled for by sonographic measurement at standard cystometric thresholds. Bladder sensitivity was also measured with complementary measures at other times separately including a simplified rapid filling test, palpation of the bladder wall, and through ambulatory self-report. Anxiety and depression were evaluated with the National Institutes of Health Patient-Reported Outcomes Measurement Information System measures. RESULTS: Women with moderate-to-severe dysmenorrhea reported more urinary symptoms than controls and had a lower maximum capacity (498 ± 18 mL vs 619 ± 34 mL, P < .001) and more evoked bladder filling pain (0-100 visual analog scale: 25 ± 3 vs 12 ± 3, P < .001). The dysmenorrhea-bladder capacity relationship remained significant irrespective of menstrual pain severity, anxiety, depression, or bladder pain (R2 = 0.13, P = .006). Severity of menstrual pain predicted evoked bladder pain (R2 = 0.10, P = .008) independent of anxiety (P = .21) and depression (P = .21). Women with moderate-to-severe dysmenorrhea exhibiting provoked bladder pain (24/98, 24%) also reported higher pain during the screening rapid bladder test (P < .001), in response to transvaginal bladder palpation (P < .015), and on prospective daily diaries (P < .001) than women with dysmenorrhea without provoked bladder pain. CONCLUSION: Women experiencing moderate-to-severe dysmenorrhea also harbor a higher pain response to naturally evoked bladder distension. Noninvasive bladder provocation needs to be tested further longitudinally in those with dysmenorrhea to characterize the course of visceral sensitivity and determine if it may help predict individuals at risk for developing subsequent pain in the bladder or elsewhere.