Kevin M Hellman , PhD

BS, Computer Science, University of Wisconsin-Madison
PhD, Neuroscience, The University of Pennsylvania
Postdoctoral Scholar, The University of Chicago

I study mechanisms and treatments for dysmenorrhea, the leading cause of school/work absence and foremost risk factor for chronic pain in reproductive age women. Our NIH and institutionally funded laboratory has developed new animal models, investigated novel diagnostic methods, and conducted treatment studies.  of our nine recent manuscripts on dysmenorrhea or related gynecological pain issues are published in the American Journal of Obstetrics & Gynecology, the most cited journal in gynecology. My goal is to advance understanding of the pathophysiology of dysmenorrhea and develop new treatments while simultaneously training a cadre of future investigators to revolutionize the science of visceral pain. Our research is essential because there are few other laboratories dedicated to eradicating dysmenorrhea, one of the most frequent causes of suffering and gender disparity worldwide.

Chronic visceral pelvic pain disorders (endometriosis-associated pelvic pain, irritable bowel syndrome, bladder pain syndrome) cause substantial morbidity, and cost upwards of 50 billion dollars in lost US wages and health care expenditures. Our research and others has shown visceral pelvic pain is common (~25% prevalence in women), but predictable and may be preventable.Two key overlapping constructs consistently convey vulnerability (odds ratio 13) as shown in large prospective studies: dysmenorrhea and widespread sensory sensitivity (i.e., somatization). Neuroplasticity is present in young girls, permitting adverse early sensory experiences to amplify future pain sensitivity. Consequently, identifying and mitigating early pain experiences might reduce their predisposition to multisensory hypersensitivity. An obvious early opportunity to explore this is at menarche, when many girls first experience menstruation-associated pain (dysmenorrhea). Consistent with prior findings, our research in over 1000 adult women found that the severity of dysmenorrhea along with self-report of sensory sensitivity predict nearly 75% of the participants who experience high levels of overall pelvic pain.¹³  Better understanding of the mechanisms responsible for dysmenorrhea and widespread sensitivity is needed to develop preventative strategies which could revolutionize current paradigms in pain management--including opioid use--the worst health epidemic of the decade.

I began studying visceral pain, widespread sensitivity, and opioid mechanisms during my postdoctoral training. I investigated the mechanisms of visceral pain and opioid analgesia. Most prior work studying descending modulation was conducted in anesthetized animals. Instead, by recording from brainstem neurons in awake animals, I substantially reformed understanding of the mechanism responsible for opioid analgesia that explains the limited effects of opioids in visceral pain, and how opioids impair respiratory and cardiovascular function. Rather than producing tonic states of analgesia or hyperalgesia, brainstem neurons dynamically boost the reaction to painful stimulation in a context-dependent manner. We demonstrated that pauses in neuronal discharge produce synchrony that facilitates postsynaptic integration. This finding has a broad impact in neuroscience, as it provides a new framework for understanding circuit function of neurons that pause in diverse brain areas. Finally, we demonstrated that opioids produce analgesia simply by disabling this pro-nociceptive circuit.Thus, our results also refute the prevailing notion of how opioids produce central analgesia and provide mechanisms to explain opioid side effects (as described in Current Opinion in Neurobiology 22:640-5).

After studying brainstem mechanisms of visceral pain modulation, I was invited to move NorthShore University HealthSystem to develop a translational research program with Dr. Frank Tu. I was inspired by Dr. Tu’s successful clinical research program studying bladder pain to expand our focus on dysmenorrhea. Together, Dr. Tu and I and co-founded the Gynecological Research Laboratory (GyRL). The goal of the GyRL research program is to identify the mechanisms that cause visceral pain, including dysmenorrhea, and develop effective interventions to prevent the development of chronic pelvic pain.The causes of visceral pain are poorly understood because diagnostic tests do not exist to distinguish pain due to primary nociceptor activation, referred abdominal muscular activity, organ perfusion, or oxygenation issues. Development of effective treatments for disruptive chronic pelvic pain conditions like dysmenorrhea and painful bladder syndrome are hindered by this lack of mechanistic understanding. The GyRL research program has addressed this gap and began work towards developing superior treatments based on our novel diagnostic research methods as described on our lab website.

• 1994: Frank Academic Scholar
• 1995: University of Wisconsin Honor Society
• 1997: Neuroscience Training Program award for Outstanding Research in Neurobiology
• 2000: National Institute of Health, National Research Service Award
• 2004: Elliot Stellar Scholar
• 2004: U.W. Madison Neuropsychology Travel Fellowship
• 2006: American Academy of Sleep Medicine Faculty Research Award
• 2012: Best abstract on pelvic pain, AAGL Global Congress
• 2012: Honorable mention poster award, International Pelvic Pain Society
• 2013: Best abstract on pelvic pain, AAGL Global Congress
• 2013: Best poster award, International Pelvic Pain Society
• 2014: New investigator of the year, NorthShore University HealthSystem
• 2016: Spotlighted abstract, Society for Affective Science
• 2017: Best paper award, Chicago Gynecological Society

• Society for Reproductive Investigation (formerly SGI)
• American Academy of Sleep Medicine
• Society for Neuroscience
• Faculty of 1000
• International Pelvic Pain Society
• International Association for the Study of Pain 

1. Lytton WW, Hellman KM, Sutula TP. Computer models of hippocampal circuit changes of the kindling model of epilepsy. (1998) Artificial Intelligence in Medicine. 13(1-2):81-97  http://dx.doi.org/10.1016/S0933-3657(98)00005-0
2. Graves LA, Hellman KM, Veasey S, Blendy JA, Pack AI, Abel T.  Genetic Evidence for a Role of CREB in Sustained Cortical Arousal. (2003) Journal of Neurophysiology 90(2):1152-9. http://jn.physiology.org/cgi/content/full/90/2/1152
3. Ouyang M, Hellman KM, Abel T, Thomas SA. Adrenergic Signaling Plays a Critical Role in the Maintenance of Waking and in the Regulation of REM Sleep. (2004) Journal of Neurophysiology. 92(4):2071-82 http://jn.physiology.org/cgi/content/full/92/4/2071
4. Keeley MB, Wood MA, Isiegas C, Stein J, Hellman KM, Hannenhalli S, and Abel T. (2006) Differential Transcriptional Response to Non-Associative and Associative Components of Classical Fear Conditioning in the Amygdala and Hippocampus. Learning and Memory 13(2):135-42.  http://learnmem.cshlp.org/content/13/2/135.long
5. Brink TS, Hellman KM, Lambert AM, Mason, P.  (2006) Raphe magnus neurons help protect reactions to visceral pain from interruption by cutaneous pain. Journal of Neurophysiology 96(6):3423-32. http://jn.physiology.org/cgi/content/full/96/6/3423
6. Hellman KM, Abel T.  Fear Conditioning Increases NREM sleep. (2007) Behavioral Neuroscience 121(2):310-323. http://psycnet.apa.org/journals/bne/121/2/310.pdf
7. Hellman KM, Brink TS, Mason, P.  Activity of murine raphe magnus cells predicts tachypnea and on-going nociceptive responsiveness. (2007) Journal of Neurophysiology 98(6):3121-33.  http://jn.physiology.org/cgi/content/full/98/6/3121
8. Hellman KM, Mendelson SJ, Mendez-Duarte MA, Russell JL, Mason P. Opioid microinjection into raphe magnus modulates cardiorespiratory function in mice and rats. (2009) American Journal of Physiology 297(5): R1400-8 http://ajpregu.physiology.org/cgi/reprint/00140.2009v1.pdf
9. Hellman KM, Hernandez, P, Young A, Park A, Abel T. Genetic Evidence that Protein Kinase A Regulates Thalamocortical Oscillations during NREM Sleep. (2010) Sleep 33(1):19-28. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2802244/
10. Tu FF, Hellman KM, Backonja M.   Gynecological Management of Neuropathic Pain. (2011) American Journal of Obstetrics & Gynecology 205(5):435-43. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3205239/
11. Hellman KM, Mason P, Opioids disrupt pro-nociceptive modulation mediated by raphe magnus. (2012) Journal of Neuroscience 40:13668-78. http://www.jneurosci.org/content/32/40/13668.long
12. Tu FF, Epstein AE, Pozolo KE, Sexton DL, Melnyk AI, Hellman KM. A Non-Invasive Bladder Sensory Test Supports a Role for Dysmenorrhea Increasing Bladder Noxious Mechanosensitivity.  (2013) Clinical Journal of Pain 29(10):883-90. http://dx.doi.org/10.1097/AJP.0b013e31827a71a3
13. Westling AM, Tu F, Griffith JW, Hellman KM, The association of dysmenorrhea with noncyclic pelvic pain accounting for psychological factors. (2013) American Journal of Obstetrics & Gynecology 209(5): 422.e1-422.e10 http://dx.doi.org/10.1016/j.ajog.2013.08.020
14. Hellman KM, Patanwala IY, Pozolo KE, Tu FF, Multimodal nociceptive mechanisms underlying chronic pelvic pain. (2015) American Journal of Obstetrics & Gynecology 213(6):827.e1-9. http://dx.doi.org/10.1016/j.ajog.2015.08.038
15. Tu FF, Kane J, Hellman KM, Non-invasive experimental bladder pain assessment in painful bladder syndrome. (2016) British Journal of Obstetrics & Gynecology 124(2):283-291. http://dx.doi.org/10.1111/1471-0528.14433     
16. Hellman KM, Yu PY, Oladosu, FA Segel C, Han A, Prasad PV, Jilling T, Tu FF. The Effects of Platelet-Activating Factor on Uterine Contractility, Perfusion, Hypoxia, and Pain in Mice. (2017) Reproductive Sciences 25(3):384-394 http://doi.org/10.1177/1933719117715122
17. Oladosu FA, Tu FF, Hellman KM. Nonsteroidal antiinflammatory drug resistance in dysmenorrhea: epidemiology, causes, and treatment. (2017) American Journal of Obstetrics & Gynecology S0002-9378(17)31095-5 http://doi.org/10.1016/j.ajog.2017.08.108
18. Hellman KM, Kuhn CS, Tu FF, Dillane KE, Shlobin NA, Senapati S, Zhou X, Li W, Prasad PV. CINE MRI During Spontaneous Cramps in Women with Menstrual Pain. (2018) American Journal of Obstetrics & Gynecology S0002-9378(18)30084-X   http://doi.org/10.1016/j.ajog.2018.01.035
19. Zuckerman R, Silton RL, Tu FF, Eng JS, Hellman KM. Somatic Symptoms in Women with Dysmenorrhea and Noncyclic Pelvic Pain. Archives of Women’s Mental Health. (2018) in press