Kevin Michael Hellman

University of Chicago | UC · Department of Obstetrics & Gynecology

Introduction Puberty encompasses a multitude of physical, hormonal, and psychological changes. Additionally, adolescents also experience a delay in circadian rhythm, increasing their vulnerability to insufficient sleep. Even though puberty and sleep share a strong association, few studies have explored the shift in sleep after the onset of menstrua...

Introduction Adolescence is marked by shifts in sleep, both in terms of timing and quality. Little is known about how these disruptions in sleep relate to pain and executive functioning (EF) following the onset of menstruation (e.g., menarche) in females. This study examines the relations between 1) sleep disturbances and pain, 2) sleep disturbance...

Multimodal hypersensitivity (MMH)—greater sensitivity across multiple sensory modalities (eg, light, sound, temperature, pressure)—is associated with the development of chronic pain. However, previous MMH studies are restricted given their reliance on self-reported questionnaires, narrow use of multimodal sensory testing, or limited follow-up. We c...

Background: Although dysmenorrhea is a highly prevalent risk factor for irritable bowel syndrome (IBS), the factors underlying this risk are not fully understood. Prior studies support a hypothesis that repeated distressing menstrual pain promotes cross-organ pelvic sensitization with heightened visceral sensitivity. Aims: To further explore cro...

Background Uterine fibroid (UF) growth rate and future morbidity cannot be predicted. This can lead to sub-optimal clinical management, with women being lost to follow-up and later presenting with severe disease that may require hospitalization, transfusions, and urgent surgical interventions. Multi-parametric quantitative magnetic resonance imagin...

Better understanding of the mechanisms underlying perceived unpleasantness in response to a stimulus are critically needed to improve the treatment of sensory disorders such as migraine and chronic pain. We previously found that generally healthy, young adult women with preclinical evidence of pelvic hypersensitivity reported greater visual unpleas...

Background and Aims: Multimodal hypersensitivity (MMH) is a hallmark symptom associated with chronic pain conditions [3–5,8,10,12,14] and mechanisms responsible for MMH may be a key reason why individuals develop chronic pain [2,7] or a determinant of treatment response [6,9]. MMH is increased sensitivity across multiple sensory modalities (e.g., l...

Women frequently report increased bloating, flatulence, and pain during the perimenstrual period. However, it is unknown whether women have more intraluminal gas during menses. To evaluate whether pain-free women or women with dysmenorrhea have different amounts of intraluminal bowel gas during the menses, we utilized magnetic resonance imaging (MR...

Dysmenorrhea is characterized by high rates of transition to chronic pain. In a previous study using structural equation modeling we demonstrated that several symptom domains associated with the emerging concept of nociplastic pain can be described using two symptom groups: generalized sensory sensitivity (GSS; composed of widespread pain, intercep...

Multimodal hypersensitivity (MMH)---greater sensitivity across multiple sensory modalities (e.g., light, sound, temperature, pressure)---is a mechanism hypothesized to be responsible for the development of chronic pain and pelvic pain. However, previous studies of MMH are restricted given their reliance on biased self-report questionnaires, limited...

Purpose of the Review Hyperalgesia may be an iatrogenic consequence of surgery or pain management. Thus, it is essential for anesthesiologists, pain management specialists, surgeons, and primary care physicians to regularly update their awareness and strategies for addressing this problem. This educational review of hyperalgesia provides up-to-date...

Although elevated estradiol levels facilitate chronic pelvic pain in animal models, it remains to be determined whether sex steroid levels are altered in a cross-section of women with chronic pelvic pain (CPP) and those at-risk for developing CPP. We sought to determine if sex steroid levels are increased in women with menstrual pain and whether th...

Introduction: Increased sensory sensitivity across non-nociceptive modalities is a common symptom of chronic pain conditions and has been shown in individuals with chronic pelvic pain (CPP); however, the neural mechanisms underlying this hypersensitivity are unknown. Understanding the brain-behavior relationships that explain multimodal hypersensit...

Increased sensory sensitivity across non-nociceptive modalities is a common symptom of chronic pain conditions and is associated with chronic pain development. Providing a better understanding of the brain-behavior relationships that underlie multimodal hypersensitivity (MMH) may clarify the role of MMH in the development of chronic pain. We studie...

Excess pain after visceral provocation has been suggested as a marker for chronic pelvic pain risk in women. However, few noninvasive tests have been validated that could be performed readily on youth in early risk windows. Therefore, we evaluated the validity and reliability of a noninvasive bladder pain test in 124 healthy premenarchal females (m...

Opioid-induced hyperalgesia (OIH) occurs when opioids paradoxically enhance the pain they are prescribed to ameliorate. To address a lack of perioperative awareness, we present an educational review of clinically relevant aspects of the disorder. Although the mechanisms of OIH are thought to primarily involve medullary descending pathways, it is li...

Objectives: Prior literature has suggested a decreased prevalence of pelvic organ prolapse (POP) in Black women. We sought to describe POP rates by race, investigate whether specific types of prolapse differ based on race, and investigate the role of uterine weight and fibroids on POP. Methods: We conducted a retrospective cohort study of new pa...

Aim: Prior research has primarily focused on static pain assessment, largely ignoring the dynamic nature of pain over time. We used a novel assessment tool for characterizing pain duration, frequency, and amplitude in women with dysmenorrhea and evaluated how these metrics were affected by naproxen treatment. Methods: Dysmenorrheic women (n = 25...

Multisensory hypersensitivity (MSH), which refers to persistent discomfort across sensory modalities, is a risk factor for chronic pain. Developing a better understanding of the neural contributions of disparate sensory systems to MSH may clarify its role in the development of chronic pain. We recruited a cohort of women (n=147) enriched with parti...

Study Objective Endometriosis-associated pelvic pain patients frequently experience both cyclical menstrual pain and chronic pelvic pain, suggesting dysregulated central sensory processes. The amount that chronic pain experience affects experimental pain sensitivity in comparison to cyclical menstrual pain exposure, is unknown. Design Subanalysis...

Objective Wikipedia is commonly used to acquire information about various medical conditions such as chronic pain. Ideally, better online pain management content could reduce the burden of opioid use disorders. Our goal was to improve the quality of the content available on Wikipedia to make it more accurate and applicable to medical students and t...

Objective Incomplete pain relief after administration of nonsteroidal anti-inflammatory drugs (NSAIDs) is common, but it is unknown whether malabsorption or heightened metabolism contributes to NSAID resistance. To explain the etiology of NSAID resistance, we evaluated naproxen absorption and metabolism in relation to pain relief in a pilot study o...

Women who develop bladder pain syndrome (BPS), irritable bowel syndrome, or dyspareunia frequently have an antecedent history of dysmenorrhea. Despite the high prevalence of menstrual pain, its role in chronic pelvic pain emergence remains understudied. We systematically characterized bladder, body, and vaginal mechanical sensitivity with quantitat...

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 t...

Background: Antecedents of chronic pelvic pain are not well characterized, but pelvic organ visceral sensitivity is a hallmark of these disorders. Recent studies have identified that some dysmenorrhea sufferers are much more likely to exhibit comorbid bladder hypersensitivity. Presumably, these otherwise healthy women may be at higher risk of deve...

Non-steroidal anti-inflammatory drugs are commonly used to treat painful periods, also known as dysmenorrhea. A subset of women, however, do not benefit from this treatment. Since the pharmacological basis of treatment resistance in dysmenorrhea has not been characterized, we assessed the relationship between measures of naproxen metabolism and sel...

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...

Somatic symptoms are a robust, transdiagnostic risk factor for pain conditions. However, the extent to which somatic symptoms contribute to the manifestation of the women’s pain syndromes, such as dysmenorrhea and noncyclic pelvic pain (NCPP), is unclear due to high rates of co-occurrence. Therefore, the present study investigated the primary hypot...

INTRODUCTION Prior research has suggested that changes in the MR signal occur in the myometrial layer in women with dysmenorrhea. Since the mechanisms of dysmenorrhea are poorly understood, characterization of the relationship between MR signal changes and spontaneous pain report would be useful for developing a diagnostic tool. METHODS This was a...

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 viscero-motor reflex resulting in involuntary skeletal muscle activity and referred pain. Although referred abdominal pain mechanisms can contribute to visceral pain, the role of...

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 whe...

Background: The lack of non-invasive methods to study dysmenorrhea has resulted in poor understanding of the mechanisms underlying pain, insufficient diagnostic tests, and limited treatment options. To address this knowledge gap, we have developed an MRI-based strategy for continuously monitoring the uterus in relation to participants' spontaneous...

Although non-steroidal anti-inflammatory drugs can alleviate menstrual pain, about 18% of women with dysmenorrhea are unresponsive, leaving them and their physicians to pursue less well-studied strategies. The goal of this review is to provide a background for treating menstrual pain when first-line options fail. Research on menstrual pain and fail...

It is widely hypothesized that menstrual pain is triggered by prostaglandin synthesis that evokes high-pressure uterine contractions and ischemia. However, the effects of molecules implicated in menstrual pain on uterine contractility, perfusion, and oxygenation in vivo have been rarely demonstrated. Studies in women that do not respond to nonstero...

Objective: To compare bladder sensitivity between patients with pelvic pain and patients who were pain free, undergoing noninvasive, controlled bladder distension via diuresis. We also sought to measure potential mechanisms underlying bladder sensitivity. Design: Prospective observational study. Setting: Community teaching hospital. Populatio...

To evaluate candidate mechanisms underlying the pelvic floor dysfunction in women with chronic pelvic pain and/or painful bladder syndrome/interstitial cystitis. Notably, prior studies have not consistently controlled for potential confounding by psychological or anatomical factors. As part of a larger study on pelvic floor pain dysfunction and bla...

Study Objective: To determine differences in pain sensitivity and psychological risk factors between women reporting improvement in pelvic pain from prior surgery vs. no improvement. The mechanisms responsible for underlying variable improvement in pain after surgery are poorly understood. Design: Cross-sectional study Setting: Academic community h...

The factors that underlie pelvic pain are poorly understood. Specifically, the relative influence of dysmenorrhea and psychological factors in the etiology of non-cyclic pelvic pain conditions, such as interstitial cystitis and irritable bowel syndrome, is unknown. To further characterize pelvic pain, we compared the frequency of menstrual, somatos...

Multimodal hypersensitivity (MMH)—greater sensitivity across multiple sensory modalities (eg, light, sound, temperature, pressure)—is associated with the development of chronic pain. However, previous MMH studies are restricted given their reliance on self-reported questionnaires, narrow use of multimodal sensory testing, or limited follow-up. We c...

Objective: Catheterization to measure bladder sensitivity is aversive and hinders human participation in visceral sensory research. Therefore, we sought to characterize the reliability of sonographically estimated female bladder sensory thresholds. To demonstrate this technique's usefulness, we examined the effects of self-reported dysmenorrhea on...

In anesthetized rats, opioid analgesia is accompanied by a specific pattern of tonic activity in two neuronal populations within the medullary raphe magnus (RM): opioids silence pain-facilitatory ON cells and produce sustained discharge in pain-inhibitory OFF cells. These tonic activity patterns, hypothesized to generate a tonic analgesic state, ha...

Obstetrician/gynecologists often are the initial management clinicians for pelvic neuropathic pain. Although treatment may require comprehensive team management and consultation with other specialists, there are a few critical and basic steps that can be performed during an office visit that offer the opportunity to improve quality of life signific...

Genetic manipulation of cAMP-dependent protein kinase A (PKA) in Drosophila has implicated an important role for PKA in sleeplwake state regulation. Here, we characterize the role of this signaling pathway in the regulation of sleep using electroencephalographic (EEG) and electromyographic (EMG) recordings in R(AB) transgenic mice that express a do...

The raphe magnus (RM) participates in opioid analgesia and contains pain-modulatory neurons with respiration-related discharge. Here, we asked whether RM contributes to respiratory depression, the most prevalent lethal effect of opioids. To investigate whether opioidergic transmission in RM produces respiratory depression, we microinjected a mu-opi...

In rats, opioids produce analgesia in large part by their effects on two cell populations in the medullary raphe magnus (RM). To extend our mechanistic understanding of opioid analgesia to the genetically tractable mouse, we characterized behavioral reactions and RM neural responses to opioid administration. d-Ala(2), N-Me-Phe(4)-Gly(5)ol-enkephali...

To understand the role that sleep may play in memory storage, the authors investigated how fear conditioning affects sleep-wake states by performing electroencephalographic (EEG) and electromyographic recordings of C57BL/6J mice receiving fear conditioning, exposure to conditioning stimuli, or immediate shock treatment. This experimental design all...

Suppression of reactions to one noxious stimulus by a spatially distant noxious stimulus is termed heterotopic antinociception. In lightly anesthetized rats, a noxious visceral stimulus, colorectal distension (CRD), suppressed motor withdrawals but not blood pressure or heart rate changes evoked by noxious hindpaw heat. Microinjection of muscimol,...

Classical fear conditioning requires the recognition of conditioned stimuli (CS) and the association of the CS with an aversive stimulus. We used Affymetrix oligonucleotide microarrays to characterize changes in gene expression compared to naive mice in both the amygdala and the hippocampus 30 min after classical fear conditioning and 30 min after...

Many experiments have suggested that the adrenergic system is important for arousal and the regulation of sleep/wake states. Electrophysiological studies have found strong correlations between the firing of adrenergic neurons and arousal state. Lesions of adrenergic neurons have been reported to cause changes in sleep/wake regulation, although find...

Sleep has been hypothesized to play a role in memory consolidation. Both sleep and memory consolidation appear to share a common pathway, the cAMP/PKA/CREB pathway. Therefore, we have examined how the effects of mutations in this pathway alter sleep as well as how learning affects sleep/wake states and gene expression. We characterized sleep in R(A...

The cyclic AMP-response element binding protein (CREB) is an activity-dependent transcription factor important for synaptic plasticity and memory storage. Levels of phosphorylated CREB within the cortex are higher in waking than in sleep, suggesting that CREB plays a role in sleep/wake regulation in mammals. We tested the hypothesis that CREB is cr...

We spend so much of our lives sleeping, yet its precise function is unclear, in spite of our increasing understanding of the processes generating and maintaining sleep. We now know that sleep can be accompanied by periods of intense cerebral activity, yet only recently has experimental data started to provide us with some insights into the type of...

Abnormalities in the organization of brain circuits may underlie many types of epilepsy. This hypothesis can best be evaluated in the case of temporal lobe epilepsy, where evidence of rewiring (synaptic reorganization) can be found in the dentate gyrus. Computer modeling of normal and reorganized dentate gyrus was used to understand the functional...

this paper are comparable to my work to be published in Artificial Intelligence in Medicine [10]. Compartmental network models and artificial network models were used to simulate the principal cells in the dentate gyrus, hippocampus. Granule cell and mossy cell models had 2 compartments, while the aspiny cell model neuron had 1. Compartmental simul...