Category Archives: News

The 2019 Southern Pain Society Conference – A Most Memorable Event

Ann Colwell-Quinlan, PhD, APN

The 2019 Southern Pain Society (SPS) conference was held September 13 through 15 in New Orleans.  We enjoyed reconnecting with those who attended previous conferences and meeting a number of first-time attendees. It was great to have a new attendee share that “this is great – so much better than I ever expected.” 

This was definitely a conference during which it would be difficult to find someone who didn’t learn at least a few new things and/or wasn’t encouraged to think about things in a new way.  A slate of well-informed speakers shared their knowledge with the attendees. 

The speakers enlightened us about the various new perspectives and options of integrated pain care.  The conference commenced on Friday afternoon with Dr. Blake Fagin providing education on prescribing controlled substances as well as how to appropriately treat patients with Substance use disorder.  Using numerous examples, he made the Louisiana mandated three hour Controlled Dangerous Substance education enjoyable while meeting the state requirements for content.  Dr. Steven Stanos opened the Saturday program by escorting us through the history of how pain professionals arrived at a new crossroads of pain management.  He then led us to comprehensively provide safe pain care.  Appreciation for and aspects of comprehensive pain management were discussed from a psychological aspect by Dr. Jennifer Murphy.  Then Dr. Jeffrey Sibrack explored the role of the endogenous opioid system with pain management. 

We learned about some innovative options on the horizon.  Dr. Ashley Mullens updated the group on the Therapeutic Cannabis Program at the LSU AgCenter including some very interesting research studies using cannabis with zebra fish and rodents.  A very timely evidence based presentation about using stem cells for pain management was given by Dr. Amadeus Mason.  Then Dr. Forest Tennant explored the role of hormones in pain control.  Monique Serpas, PT, DPT shared the various analgesic techniques used by physical therapists. She and Dr. Stanos both discussed the importance of function in pain control. In a sense Dr. Dan Doleys brought us full circle by updating on screening for opioid use disorder prior to starting opioids.  We concluded with Dr. Charles Figley educating us about and encouraging us to pursue commitments to self-care personally and to support other members of SPS in pursuing the same for themselves.  We also were fortunate to view several excellent posters.

For me our annual business meeting was an amazing event.  First, I had the pleasure to present the President’s Award for Distinguished Service to the SPS to Dr. Thomas Davis who has served as secretary of SPS for many years as well as co-chair of this amazing 2019 conference.  During that time Dr. Davis has always had a calm, even, well-balanced approach to any issue that arose. Then, Dr. John Satterwaite presented the 2019 Hubert L. and Renee S. Rosomoff Award for Excellence in Pain.  I can only remember having an intense emotional response when I heard him say my name.  To say that I was speechless is an underestimation.  I doubt there is any greater honor than to be recognized for excellence by professional peers and partners.  Now that I have regained cognition, I am extremely honored and appreciative to have been selected to receive this prestigious award.  I also am very appreciative for all of the wonderful teachers, mentors, peers and especially patients who have taught me so much about working with people who live with pain.   It certainly is incentive to continue to work with SPS to pursue our mission “to serve people with pain by advancing research and treatment and to increase the knowledge and skill of the regional professional community.” 

My appreciation also goes to our planning committee led by Drs. Geralyn Datz and Thomas Davis; the SPS board, our Executive Director Lori Postal, the amazing presenters, Lisa and Wilma from MAHEC; and Chris Hall who did his magic with the audio visuals  for all of their efforts in making the 2019 SPS conference a fantastic experience.

Disparities in Pain and Pain Care: Combating Bias in Practice

Jennifer L. DelVentura, Ph.D., ABPP
Jennifer L. Steiner, Ph.D., ABPP

In a post in a previous issue of this newsletter, titled “Gender disparities in Pain and Pain Care,” we explored the evidence that women are not only at higher risk for pain and pain conditions but that their pain appears to be underestimated and, in some cases, undertreated compared with men’s pain. Similar patterns are evident in diagnosis and treatment of pain in racial/ethnic/SES minority patients, ranging from differences in prevalence and severity of pain in these groups to differential access to resources and pain care.

While there are many factors operating at different levels (community, institutional/systemic, familial/social, individual) contributing to these disparities, the impact of provider biases on pain care is of particular interest for us, as clinicians.  Biases are ubiquitous, often unconscious, and a normal part of human cognition, but they are not innocuous.  They may even be inconsistent with conscious beliefs—e.g., one may deny having negative beliefs about minority groups, but still evidence presence of unconscious biases in decision-making.  But importantly, with awareness and effort biases are malleable.  It is our task as ethical, caring providers to strive to minimize the impact of harmful biases on patient care.   

Using measurement tools normed for minority populations

One approach to reducing impact of biases involves using pain assessment tools normed for minority patient populations.  Even seemingly unbiased tools may be interpreted and rated differently by minority groups.  Take for example the widely-used numerical pain rating scale with verbal anchors (e.g., “moderate,” “severe” or “worst pain imaginable”) to describe pain intensity.  While these scales appear bias-free, their use rests on the assumption that we all interpret pain descriptors in the same way.  Yet this may not be true, as is demonstrated in a study by Campbell and colleagues[1], comparing pain ratings to thermal stimuli in men vs. women and white vs. black participants.  Findings indicated that when using a generic numerical pain rating scale, women and black participants rated the stimuli as significantly more painful than their counterparts.  However, when participants were allowed to individualize the rating scale by moving the verbal anchors to reflect their subjective interpretation of pain, group differences in pain ratings were no longer significant[1] suggesting group differences in how these anchors were interpreted, perhaps attributable to culture, socialization, or other factors.

The Campbell et al [1] study points to the need for measures modified for or normed to different populations.  Indeed, a few measures with such norms do exist.  For example, for psychologists, the MMPI-II-RF and Millon Behavioral Medicine Diagnostic [2], offer a multitude of specific patient group norms divided by gender (but not ethnicity).  Additionally, several behavioral measures of functioning that are commonly used by physical therapists now have more extensive norms for different populations. The unipedal stance (UPST) now has norms for age and gender [3] and several other common tests such as the timed up-and-go test and single limb stance test have established significant differences based on age [4-6].  However, most measures lack norms specific to race/ethnicity, and thus this remains an important area of development for the field of pain management.  Because such minority group norms are not widely available, it is crucial to be aware of the inherent limitations of our commonly used measures.

Provider-level strategies for managing bias

But what else can providers do to reduce impact of bias on patient care?  Social psychology research offers valuable insights into strategies for addressing biases in our work.  Based on this research, Burgess and colleagues [7] put forth a multi-step, evidence-based framework for addressing biases in healthcare, parts of which we will briefly summarize here.

First, fostering providers’ internal motivation for change is foundational to this model and involves bringing awareness to the presence of biases in our work.  This can be done using techniques like the implicit association test (IAT, [8, 9], a measure of response latency that evaluates the strength of an association between pairs of contrasting concepts and is believed to tap into implicit connections between concepts in the brain. The IAT takes advantage of the brain’s inherent tendency to pair concepts together in service of faster processing, the more closely two concepts are linked together for an individual, the faster the person should be able to respond when one component of the pair is activated in the brain. It is a computer-administered task that has been used to highlight unconscious biases or preferences for people that belong to particular social groups (race, gender, religion., etc.), however, it is important to note that there is some debate as to what the IAT actually measures, and whether implicit bias is correlated with explicit bias and/or explicit behavior [10, 11]. Nevertheless, completing an IAT for a number of variables, i.e. gender, race, size, etc. (at[1] may offer some insight into our own associations and may inform self-reflection.

To give an example of what such an exercise might look like we invite you to consider the following sentences (adapted from the group exercise described in Holm et al., 2017) and count how many are true for you:

  • I can feel confident that others feel that I am qualified upon first impression.
  • I can speak in a roomful of medical providers and feel that I am heard.
  • My age adds to my credibility.
  • When I report pain or physical symptoms to my doctor, I can feel confident that my race or gender identification will not work against me.
  • When I report pain or physical symptoms to my doctor, I can feel confident that others will take them seriously and not assume I am motivated by secondary gain.
  • I can feel confident that if a family member requires hospital or emergency treatment they would be treated with dignity and respect even if they don’t mention my connection with the hospital.

Consider what you notice here.  How many feel true for you? And how might this reflect privilege (or lack thereof) in a healthcare environment? The intention here is not to blame or shame individuals who carry privilege, but rather to consider how this privilege might impact our experience and the quality of care we receive [7, 12].

Now, we invite you to bring to mind a patient or acquaintance with minority group affiliations (race, gender, age, SES). Then with this patient in mind, read through and consider these sentences again from this person’s perspective.  How many of these might feel true to this person?  And in turn, how might this impact actual or perceived care?  The answers and experience might be rather different in this case, and may be uncomfortable for us to consider.  Indeed, it is common for exercises like the above to elicit some negative emotions and internal discomfort (e.g., cognitive dissonance).  However, when elicited in a safe, nonjudging environment, these negative emotions can serve to motivate behavior change.  

Other strategies and considerations for providers

Other steps in the Burgess et al [7] model include increasing contact and comfort with minority groups, and facilitating perspective-taking and empathy for minority group patients—e.g., imagining situations from the patient’s perspective.  However, empathy can suffer due to stress, burnout, and time (e.g., over the course of one’s career).  Even when great strides have been made in reducing the impact of biases and increasing awareness of one’s biases, as creatures of habit we tend to regress back into old patterns if not careful.  Thus, self-care and becoming attuned to our own needs is vital to reducing bias in our work.  It is important that providers practice recognizing signs of burn-out within themselves and routinely re-assess for potential biases. At a systems level, this perhaps highlights the need for greater resources, i.e. advocating for lighter patient caseloads, more time with patients, more time for education (such as seminars or experiential trainings) of this nature both during graduate-level training and at the post-licensure level, and more.

All considered, it is important to note that perfection is neither expected nor realistic in efforts to reduce negative impacts of biases.  Rather, we should strive to reduce biases through practice of empathy, perspective-taking, awareness, and seeing patients as individuals rather than through the lens of group membership.


  1. Campbell, T.S., et al., Relationship of ethnicity, gender, and ambulatory blood pressure to pain sensitivity: Effects of individualized pain rating scales. The Journal of Pain, 2004. 5(3): p. 183.
  2. Millon, T., et al., Millon Behavioral Medicine Diagnostic. 2001, Minneapolis, MN: NCS Assessments.
  3. Springer, B.A., et al., Normative values for the unipedal stance test with eyes open and closed. J Geriatr Phys Ther, 2007. 30(1): p. 8-15.
  4. Hirano, K., et al., Impact of low back pain, knee pain, and timed up-and-go test on quality of life in community-living people. J Orthop Sci, 2014. 19(1): p. 164-71.
  5. Bohannon, R., Single limb stance times: a descriptive meta-analysis of data from indivdiuals at least 60 years of age. . Topics in Geriatric Rehabilitation, 2006. 22(1): p. 70-77.
  6. Steffen, T.M., T.A. Hacker, and L. Mollinger, Age- and gender-related test performance in community-dwelling elderly people: Six-Minute Walk Test, Berg Balance Scale, Timed Up & Go Test, and gait speeds. Phys Ther, 2002. 82(2): p. 128-37.
  7. Burgess, D., et al., Reducing racial bias among health care providers: lessons from social-cognitive psychology. J Gen Intern Med, 2007. 22(6): p. 882-7.
  8. Greenwald, A.G., D.E. McGhee, and J.L. Schwartz, Measuring individual differences in implicit cognition: the implicit association test. J Pers Soc Psychol, 1998. 74(6): p. 1464-80.
  9. Nosek, B.A., A.G. Greenwald, and M.R. Banaji, Understanding and using the Implicit Association Test: II. Method variables and construct validity. Pers Soc Psychol Bull, 2005. 31(2): p. 166-80.
  10. Lane, K.A., et al., Understanding and using the implicit association test: IV. Implicit Measures of Attitudes, 2007: p. 59-102.
  11. Hofmann, W., et al., A meta-analysis on the correlation between the implicit association test and explicit self-report measures. Pers Soc Psychol Bull, 2005. 31(10): p. 1369-85.
  12. Holm, A.L., et al., Recognizing Privilege and Bias: An Interactive Exercise to Expand Health Care Providers’ Personal Awareness. Acad Med, 2017. 92(3): p. 360-364.

[1] is run by a non-profit organization and collects the data for scientific purposes.

[2] The Cultural and Linguistic Competence Health Practitioner Assessment (CLCHPA) through the Georgetown University National Center for Cultural Competence can be found at  Please note that the assessment and website are temporarily out of service for revisions

Hypnotically Enhanced Addictions Treatment

Joseph Tramontana, Ph.D.

As a member of the Board of Directors of the Southern Pain Society, I want to share with the membership a recent workshop I presented to the Canadian Federation of Clinical Hypnosis in Banff, Canada.  The workshop was titled “Hypnotically Enhanced Addictions Treatment: Drug Abuse, Alcoholism and Alcohol Abuse, Gambling Addiction, Smoking Cessation, and Obesity, with a Focus on Drug Dependence during this Opioid Crisis.”

The 2-day workshop was presented by invitation to a group of 19 advanced hypnosis practitioners, including MDs, Psychologists, Licensed Clinical Social Workers, and Licensed Counselors.

While the title was lengthy, a number of problem behaviors were addressed. Dealing with pain patients, was a major focus. For example, if a patient came in experiencing pain at a “7,” (on a 10-point scale)  and after the first hypnosis session he/she reported it was down to a “3,” the change was not only significant, but interpreted to them as “probably as much relief as you get from a pain pill, but it’s natural.” More importantly, the patient is taught self-hypnotic techniques to use at home as a coping skill. The goal is to use hypnotic relaxation when hurting instead of instinctively reaching for the pill bottle. 

Another technique is having the patient, while in trance, imagine the sensation of pain medication, but replicating the relief without the actual medicine.

These techniques fit well with psychoeducation interpretations to patients about the “Mind-body connection.”

Helping Patients Get Their Life Back Through Acceptance and Commitment Therapy

Jennifer L. DelVentura, PhD ABPP
Jennifer L. Steiner, PhD ABPP

“I just want my life back, I want to feel like me again”. This is a common refrain in our work as pain psychologists. Too often individuals with chronic pain feel as though their lives have fundamentally changed from ones defined by activity and engagement in a meaningful life to ones full of limitations, isolation, and feelings of loss. Many feel unable to move forward in their lives without elimination of the pain and find themselves stuck in an endless search for a cure, spending enormous amounts of energy, money, and time searching for the next best treatment or the “right” doctor. For these patients, life becomes about escaping the pain and no longer about living. But escape from pain is short-lived, and often comes at a price–from medications that offer temporary relief while also reducing functioning due to drowsiness, to self-medication with alcohol, drugs, or food which offer short bursts of pleasure or distraction, but serve to worsen pain, depression, and isolation over time. Of course, patients want the pain to be eliminated, but often what is most distressing about a life with pain is the loss of the sense of self, meaning, and purpose.

Indeed, research has demonstrated that individuals with chronic pain experience a change in self-concept after the onset of chronic pain (Harris, Morley, & Barton, 2003; Hellstrom, 2001; Leventhal, Idler, & Leventhal, 1999). For example, patients may feel that they are no longer the person they were prior to pain and may go through a period of mourning the loss or death of the “past self”. Others go through feelings of loss for the future “possible self,” “what could have been,” and plans that they envisioned for themselves that they fear will never come to fruition due to their pain condition. Some individuals may fluctuate between both of these experiences. It is perhaps not surprising then that depression is highly comorbid with chronic pain, and for some individuals much (though not all) of this can be attributed to the changes in quality of life and sense of self observed with pain.

Acceptance of Pain

Traditional treatment approaches often focus on symptom reduction and “fixing” the problem of pain, leaving patients feeling frustrated, discouraged, and depressed when the pain is not sufficiently alleviated. But what if the pain did not have to be “fixed” in order to improve functioning and quality of life?

Acceptance of chronic pain and illness has been a growing area of interest over the past 20+ years and has been defined as “acknowledging that one has pain, giving up unproductive attempts to control pain, acting as if pain does not necessarily imply disability, and being able to commit one’s efforts toward living a satisfying life” (McCracken, 1998, p. 22). It does not mean that one “gives in” to the pain and succumbs to an unsatisfactory life; but rather, that one makes a conscious decision to fully live with the chronic pain or illness while still being aware that the condition may not improve. One of the foundational theoretical underpinnings of acceptance-based approaches is that it is actually the lack of engagement in meaningful life experiences and activities, not the pain itself, that leads to suffering. Through acceptance it is believed that individuals change their relationship with their pain and how pain impacts their quality of life. Indeed, greater pain acceptance has been shown to be associated with better mental health outcomes physical functioning, quality of life, etc. (McCracken, 1998; Viane et al, 2003).

Acceptance and Commitment Therapy (ACT, pronounced like the verb “act”) for pain is an evidence-based psychological intervention aimed at increasing pain acceptance. ACT helps patients to realize that many of the things they do to try to control pain (e.g., avoidance or self-medication) may actually cause further damage to health, emotional state, and quality of life in the long-run. For example, many of the patients with whom I [JLS] work have said that they spend most of the day resting or “waiting for the pain to subside” before they will do anything (play with children, get dressed, complete small chores around the house, etc.). As a result, patients often end up waiting all day, and sometimes weeks, before anything gets done. In ACT, the therapist helps the patient realize that waiting for pain to go away is futile and unproductive as the pain is always present (indeed, it is “chronic”!). This is done in part through helping the patient explore what matters to them (personal values) and helping them find a way to pursue those actions even in the presence of pain. Through a combination of ACT techniques that include collaborative evaluation of the utility of pain reduction and avoidance strategies, exploration of personal values, values-based goal setting, and mindfulness, patients regain a sense of control over their lives so that they are dictating their actions rather than allowing pain to control all of their life choices. This makes for happier patients and more successful encounters for providers. The key is helping patients see that they don’t have to completely give up on what matters to them, but to flexibly find ways to pursue their dreams even if it looks differently than what they originally had in mind.

Take for example a patient I [JLS] worked with who was a former college athlete and had lifelong dreams of teaching his sons to play soccer. However, chronic lower back issues had made it impossible for him to play with them. Together we devised a way for him to engage in teaching his sons the game, even if he could not physically participate. He now helps coach his sons’ soccer team, watches game tapes with them, and attends all of their games. His pain is still present and he has continued to experience some physical limitations; however, he has said that he is less focused on his pain. As a result of being able to do more with his children, he reported decreases in depression and increased quality of life.

ACT for chronic pain is considered to have strong empirical support based on guidelines outlined by the American Psychological Association (APA). Meta-analytic work examining ACT for Chronic pain has demonstrated that ACT is associated with positive effects on depression, disability, and quality of life, as well as modest effects on anxiety and pain interference (Veehof, Oskam, Schreurs, & Bohlmeijir, 2011; Veehof, Trompetter, Bohlmeijir, & Schreurs, 2016). These studies suggest that effects from ACT are comparable to effects from CBT, though some studies that have directly compared the two common interventions have found greater patient satisfaction associated with ACT (Wetherell, 2011). Unlike cognitive behavioral therapy (CBT; long known as the “gold standard” of psychological treatments for chronic pain), which often places emphasis on symptom reduction and changing maladaptive thoughts about pain, ACT emphasizes increasing quality of life through values-based behavior and letting go of attempts to control or avoid the pain that have ultimately proven to be unproductive. ACT (compared with TAU) is also associated with reduced absence from work and utilization of medical resources due to pain with some of these changes maintained at follow-up (Dahl et al, 2004).

A note about what ACT is NOT.

There is a common misconception that ACT for chronic pain is akin to telling patients to “suck it up and do it anyway”. That is not what we are suggesting. Rather, from an ACT perspective to improve patient quality of life we must find a way to help the individual pursue values in different ways and stop waiting for pain to go away, as that day may never come. Similarly, ACT does not propose that patients give up any and all pain management strategies, but to consider the effectiveness or workability of these strategies and give up the ones that interfere with values or quality of life.


Finding a therapist trained in ACT is not always easy. We encourage referring providers to be aware that not all pain psychologists are trained in ACT, and not all ACT therapists have experience with chronic pain. A good place to start is the Provider Directory through SPS and outreaching these psychologists directly to ask about their expertise or recommendations for other providers in your area. Most states also have State Psychological Associations with member directories that often list providers’ areas of expertise as well.

You can also search for providers in your area through the Association for Contextual Behavior Science (ACBS) website at this link:*

Most of us may agree helping patients with chronic pain can be challenging, and we may not always be able to “cure” or even reduce the pain. However, through interventions like ACT and focus on finding new ways to pursue a meaningful life, we may be able to reduce suffering. Isn’t that really the point?

*Please be aware that providers listed on this website are self-identified as ACT providers, and expertise in chronic pain is not guaranteed.


Dahl, J., Wilson, K. G., & Nilsson, A. (2004). Acceptance and commitment therapy and the treatment of persons at risk for long-term disability resulting from stress and pain symptoms: A preliminary randomized trial. Behavior therapy, 35(4), 785-801.

Harris, S., Morley, S., & Barton, S. B. (2003). Role loss and emotional adjustment in chronic pain. Pain, 105(1-2), 363-370.

Hellström, C. (2001). Temporal dimensions of the self-concept: Entrapped and possible selves in chronic pain. Psychology and Health, 16(1), 111-124.

Leventhal, H., Idler, E. L., & Leventhal, E. A. (1999). The impact of chronic illness on the self system. Rutgers series on self and social identity, 2, 185-208.

McCracken, L. M. (1998). Learning to live with the pain: acceptance of pain predicts adjustment in persons with chronic pain. Pain, 74(1), 21-27.

Veehof, M. M., Oskam, M. J., Schreurs, K. M., & Bohlmeijer, E. T. (2011). Acceptance-based interventions for the treatment of chronic pain: a systematic review and meta-analysis. PAIN, 152(3), 533-542.

Veehof, M. M., Trompetter, H. R., Bohlmeijer, E. T., & Schreurs, K. M. G. (2016). Acceptance-and mindfulness-based interventions for the treatment of chronic pain: a meta-analytic review. Cognitive behaviour therapy, 45(1), 5-31.

Viane, I., Crombez, G., Eccleston, C., Poppe, C., Devulder, J., Van Houdenhove, B., & De Corte, W. (2003). Acceptance of pain is an independent predictor of mental well-being in patients with chronic pain: empirical evidence and reappraisal. Pain, 106(1-2), 65-72.

Wetherell, J. L., Afari, N., Rutledge, T., Sorrell, J. T., Stoddard, J. A., Petkus, A. J., Solomon, A.J., Lehman, D.H., Liu, L., Lamg, A.J., & Atkinson, J. H. (2011). A randomized, controlled trial of acceptance and commitment therapy and cognitive-behavioral therapy for chronic pain. Pain, 152(9), 2098-2107.

Gender Disparities in Pain and Pain Care

Jennifer L. DelVentura, Ph.D., ABPP
Jennifer L. Steiner, Ph.D., ABPP

In a widely-shared article published in the Atlantic in 2015, titled “How Doctors Take Women’s Pain Less Seriously,” author Joe Fassler tells of his wife Rachel’s visit to the ER after she is suddenly stricken with excruciating abdominal pain, later revealed to be a life-threatening ovarian torsion [1]. The article tells of their agonizing 14-hour wait in the ER for evaluation and treatment while Rachel’s pain is dismissed (“You’re just feeling a little pain honey”), undertreated, and summarily misdiagnosed as kidney stones without full examination. While Rachel survives the experience, she describes being left with “the trauma of not being seen,” and suffers physical and emotional scars in the aftermath. This story is notable not because of the long wait in the ER, which is often routine, but because it points to a more insidious problem in how we view and respond to women’s pain in healthcare.

Ample research indicates that gender biases impact our treatment of patients with pain, including how we interpret the nature and severity of that pain. Take for example a study examining how clinicians perceive patient reports (verbal and nonverbal) of pain severity [2]. In the study, clinicians viewed video of male and female patients, all with shoulder pain and all undergoing painful manipulation procedures. Despite similar conditions and presentation, female patients were judged to be in significantly less pain than their male counterparts and were seen as significantly more likely to exaggerate their pain. Indeed, the more a female patient was perceived to be exaggerating her pain the lower the clinicians judged her actual pain to be, while the same relationship did not hold true for male patients (e.g., perceived exaggeration did not significantly impact judgments of pain severity) [2].

In a similar study in children, Yale researchers showed clinicians video of a child crying in pain during a fingerstick blood test and asked the clinicians to judge the pain the child experienced [3]. The child, whose observable gender characteristics were ambiguous, was referred to by either a male or female name. The authors found that the “boy” child was judged to be experiencing significantly more pain than the “girl” despite identical circumstances (in fact, the same child). Perhaps more unexpectedly, it was largely the women clinicians’ ratings that drove the observed biases in pain ratings, making clear that women are not immune to gender biases.

Extending this further, research demonstrates that gender can play an influential role in how clinicians diagnose and treat pain. A few studies have tested this by asking providers to evaluate case vignettes of patients that vary only in gender (and in some cases race) of the fictional patient. When the patient is identified as female, providers are more likely to reference psychosocial factors in the case history [4], more likely to offer nonspecific diagnoses (e.g., “myalgia”) [4], more likely to recommend antidepressants or mental health referrals [5, 6], and less likely to prescribe higher doses of pain medications (compared to when the patient is identified as male; [6]). Here too, women providers often demonstrated as much, if not greater, influence of gender bias in decision-making [4, 5].

This apparent underestimation and under-treatment of women’s pain occurs in the context of decades of research demonstrating that women are disproportionately burdened with pain. Globally, women are diagnosed with chronic pain conditions at higher rates than men [7] and often report greater severity of pain on average compared with men with those same chronic pain conditions [8]. Even in healthy (chronic pain free) individuals, women appear to be more pain-sensitive (have lower pain thresholds/tolerances) across a range of stimulus types (pressure, thermal, electrocutaneous [9, 10]) compared with men. 1

The factors underlying these differences are manifold, including biological, psychological, and sociocultural influences. And some of these factors may also function to disadvantage men suffering with pain. For example, evidence suggests women are viewed as more willing to express pain compared with men [12] and doing so is less inconsistent with traditional gender roles [13], and hence more acceptable. Likewise, women are known to access healthcare at higher rates than men [14], perhaps contributing to underrepresentation of men seeking medical care for pain. Thus, one could postulate that men suffer similarly from pain but are more reluctant to endorse or seek care for it, due to fear of stigma.

While the above is hardly an exhaustive review of the evidence, it is clear that observed gender differences in pain experience and pain care are consistent, concerning, and complex. Lack of acknowledgement and attention to these differences risks invalidating women’s pain experience, as well as underdiagnosing and undertreating their pain symptoms. And yet, this should not be interpreted as an attempt to place blame or suggest harmful intent on the part of providers. Indeed, such biases are often wholly unconscious. This was illustrated in a study of race and gender influences on treatment-planning in medical trainees, in which not only did race and gender factors significantly influence decision-making for at least 30% of the trainees, but at least 50% of them were unaware their biases [6]. As human beings, we all rely on mental heuristics when short on time, pulled in too many directions, feeling pressured, or dealing with ambiguous situations [15, 16]—as is common in any pain management setting. But these heuristics are fallible and, simply put, it is our responsibility as ethical providers to work to recognize these biases and then to reduce harmful effects of them.

So how do we begin to address these issues? In the words of Sir Francis Bacon, ipsa scientia potestas est–knowledge itself is power [17]. Educating ourselves about disparities in pain and pain treatment is an important first step. This includes practicing conscious self-reflection on biases and heuristics in decision-making as well as seeking out experiences and educational opportunities that help us learn to challenge them. At a broader level, evidence-based and patient-centered care can be supported through further development and use of clinical assessment tools normed for gender and minority populations as well as expanding gender and multiculturally-sensitive curricula in medical and graduate training. Lastly, future research should work to validate and disseminate methods for reducing impact of biases in health care. Social and cognitive psychology research supports a multimodal approach to bias-reduction that includes enhancing provider motivation for change, an emphasis on patient individuation vs. categorization, increasing perspective-taking, and improving provider-patient collaboration [18]. These strategies will be discussed in more detail in a future issue of this newsletter.

1 Colloquial wisdom asserts just the opposite, on the basis of women’s ability (and willingness) to tolerate the immense pain of childbearing.  The duration (e.g., acute vs. chronic), perceived cause, and one’s appraisals of pain significantly impact the pain experience.  For an interesting review of pain coping factors, see: 11.    Jensen, M.P., et al., Coping with chronic pain: A critical review of the literature. Pain, 1991. 47M: p. 249.


1. Fassler, J., How Doctors Take Women’s Pain Less Seriously, in The Atlantic. 2015.
2. Schafer, G., et al., Health care providers’ judgments in chronic pain: the influence of gender and trustworthiness. Pain, 2016. 157(8): p. 1618-25.
3. Earp, B.D., et al., Gender Bias in Pediatric Pain Assessment. J Pediatr Psychol, 2019.
4. Hamberg, K., et al., Gender bias in physicians’ management of neck pain: a study of the answers in a Swedish national examination. J Womens Health Gend Based Med, 2002. 11(7): p. 653-66.
5. Hirsh, A.T., et al., The influence of patient sex, provider sex, and sexist attitudes on pain treatment decisions. J Pain, 2014. 15(5): p. 551-9.
6. Hollingshead, N.A., et al., Impact of race and sex on pain management by medical trainees: a mixed methods pilot study of decision making and awareness of influence. Pain Med, 2015. 16(2): p. 280-90.
7. Fillingim, R.B., et al., Sex, gender, and pain: a review of recent clinical and experimental findings. J Pain, 2009. 10(5): p. 447-85.
8. Ruau, D., et al., Sex differences in reported pain across 11,000 patients captured in electronic medical records. J Pain, 2012. 13(3): p. 228-34.
9. Racine, M., et al., A systematic literature review of 10 years of research on sex/gender and experimental pain perception – part 1: are there really differences between women and men? Pain, 2012. 153(3): p. 602-18.
10. Rhudy, J.L., et al., Are there sex differences in affective modulation of spinal nociception and pain? J Pain, 2010. 11(12): p. 1429-41.
11. Jensen, M.P., et al., Coping with chronic pain: A critical review of the literature. Pain, 1991. 47M: p. 249.
12. Robinson, M.E., et al., Gender role expectations of pain: relationship to sex differences in pain. Journal of Pain, 2001. 2(5): p. 251-7.
13. Williams, J. and D. Best, Cross-cultural views on men and women, in Psychology and Culture, W. Lonner and R. Malpass, Editors. 1993, Pearson.
14. Bertakis, K.D., et al., Gender differences in the utilization of health care services. J Fam Pract, 2000. 49(2): p. 147-52.
15. Wigboldus, D.H., et al., Capacity and comprehension: Spontaneous stereotyping under cognitive load. Social Cognition, 2004. 22(3): p. 292-309.
16. Kahneman, D., S.P. Slovic, and A. Tversky, eds. Judgment under uncertainty: Heuristics and biases. 1982, Cambridge University Press.
17. Bacon, F., Meditationes Sacrae. 1597: Londini. : Excusum impensis Humfredi Hooper.
18. Burgess, D., et al., Reducing racial bias among health care providers: lessons from social-cognitive psychology. J Gen Intern Med, 2007. 22(6): p. 882-7.

Ajovy and Emgality: Efficacy and Side Effects

Lawrence Robbins, M.D. 

NOTE: Data was collected from Oct. 2018 through May, 2019. Data was collected by Dr. Robbins and Brook Phenicie, NP-C. This was a de-identified retrospective study. IRB was obtained This write-up is preliminary.

All patients had the diagnosis of chronic migraine. Almost all patients had utilized Botox for their chronic migraine. Each patient had utilized at least 3 preventive medications in the past. Many of these patients remained on a daily preventive. Approximately 60% of the patients were considered to have refractory chronic migraine (European Headache Federation definition). The primary data point was the degree of relief obtained during the initial 3 months. Relief was determined by: the percentage decrease (versus baseline) in the number of migraine days, combined with the number of moderate or severe headache days (even without features of migraine).

Moderate or severe days were assessed via a 10-point VAS. Relief was averaged for the entire first 3 months. If patients discontinued the mAb prior to completing 3 months of treatment, relief was considered to be 0%. Consents were obtained.

Ajovy: Efficacy After 3 Months

N=79(68F, 11M)

0 to 30% relief: 50% of patients
31 to 70% relief: 33%
71 to 100% relief: 18%
Subset: Combined (31 to 100% relief): 51%
Subset: Patients with 95 to 100% relief: 8%

Ajovy: Side Effects

Nausea: 6% Constipation: 6% Depression: 6%
Increased headache: 5% Muscle pain and/or cramps: 5%
Rash: 4% Joint pain: 4% Anxiety: 4% Fatigue/tiredness: 4%
Weight gain: 4% Injections site reactions: 3% Irritability: 3% Alopecia: 3% Diarrhea: 1% Weight loss: 1% Shingles(recurrent): 1%

Emgality: Efficacy after 3 months

N=70(56F, 14M):

0 to 30% relief: 40%
31 to 70% relief: 46%

71 to 100% relief: 14%
Subset: Combined (31 to 100% relief): 60%
Patients with 95 to 100% relief: 3%

Emgality Side Effects

Constipation: 10% Depression: 6% Increased Headache: 6%
Fatigue/tiredness: 4% Nausea: 4% Injection site reaction: 4%
Weight gain: 3% Alopecia: 3% Muscle pain and/or cramps:3%
Anxiety: 3% Rash: 3% Insomnia: 1% Weight Loss: 1%


Efficacy: The efficacy for Ajovy and Emgality is reasonable (50 to 60% of patients report at least a 31% improvement over the first 3 months). The difference in efficacy between Ajovy and Emgality is probably not significant. Ajovy was frequently prescribed for those who had failed on Aimovig (during October and November, 2018), and this may have artificially lowered the Ajovy results. This efficacy is similar to what we reported for Aimovig (we found that 58% of those on Aimovig achieved at least a 31% improvement). This efficacy is similar to what is generally reported with the use of Botox. As is the case with Botox, there is a small percentage of patients who do extremely well (95 to 100% improvement).

Over time, our Aimovig study indicated that some patients do find the mAb “wearing off’. This seems to happen in a small but significant minority of people. Anecdotally, we have found that Botox seems to “wear off” at a lower rate than is observed with the CGRP mAbs.

We are currently assessing the month to month effect of Ajovy and Emgality over 8 months. With Aimovig, we found that, after month 2, it was somewhat predictable what would happen over the next 4 months. We are also studying the effect of a CGRP mAb combined with Botox.

Side Effects: This is where the formal Phase 2 and 3 mAb studies are not accurate. The CGRP mAbs produce a plethora of side effects, most of which are mild. Sometimes these are transient, but often they do not diminish. As of 3/31/2019, on the FDA FAERS website, there were 12,000+ side effects reported for Aimovig, with 1,200+ serious side effects. Ajovy and Emgality had smaller numbers. In our Aimovig, Ajovy, and Emgality studies, we encountered a number of side effects that were not reported in the companies’ studies. I have used 4 sources to evaluate side effects in this class: 1. Our own patients, 2. The CGRP patients chat boards (over 16,000 patients), 3. Physician communications, and 4. The FDA FAERS website. It appears as if Aimovig may produce more side effects than Ajovy/Emgality, but this is a preliminary observation. We encountered 3 serious side effects from Aimovig; only one from Ajovy (recurrent shingles: possibly coincidence), and none due to Emgality.

It may be that the portions of the brain not protected by the blood brain barrier produce some of the central side effects. These include the hypothalamus, pituitary, area postrema, and the choroid plexus. Weight gain, anxiety, and depression may be accounted for via perturbations of the HPA axis, in which CGRP plays a prominent role. We need the FDA, with help from the companies, to update the PI. Serious side effects need to be further evaluated in a comprehensive fashion.

President’s Message on the American Pain Society

Dear SPS Member:

The members of the Board of Directors of the Southern Pain Society were saddened to read about the possible need for the American Pain Society to cease operations.  We have long appreciated the scientific contributions and clinical guidelines for pain management made by the APS. 

We also want to re-assure members of the Southern Pain Society that, thanks to your support, we continue to be a healthy and viable organization dedicated to “serve people with pain by advancing research and treatment and to increase the knowledge and skill of the regional professional community” of the 18 southern states and Puerto Rico. Although we were considered a regional society by APS, we were and continue to be a separate and distinct entity with our own corporate and tax identity.  There are no legal or financial ties to APS. 

We are finalizing our plans for our annual meeting dedicated to exploring an Integrative Pain Care: New Perspectives, which will be held this year in New Orleans from September 13-15.  Hopefully, you will join us there to learn about a variety of pain management options from our group of expert presenters. 


Ann Quinlan-Colwell, APN, PhD
Southern Pain Society


President’s Message, April 2019

Ann Quinlan-Colwell, PhD, APN

While reviewing the agenda for our upcoming annual Southern Pain Society meeting Integrated Pain Care: New Perspectives, after looking at the varied topics being presented and the backgrounds of the speakers, I was reminded of the concept that “it takes a village.”  Considering that phrase led me to investigate the term and asses if it was reasonable to  make that connection with our conference.  Surprisingly, the first definition I found was in the Urban Dictionary which explained the phrase it takes a village is used to describe the enormity of a difficult task or how many people are needed to “clean up the mess.”  Although that wasn’t the connection I initially made between our conference and the phrase, it certainly resonated with our intent for the conference in relation to the current dual opioid and pain crises.  Along with the attention the opioid crisis is receiving, those of us working daily with patients living with pain know that for many of them there is a simultaneous pain crisis.  As pain professionals we have a responsibility to help to “clean up” what many consider to be  “the mess” that resulted from the opioid crisis and now the consequential pain crisis.  We also are well aware that the task is far from easy (i.e. difficult).

Although it was tempting to be content with the Urban Dictionary definition, I knew there are other meanings.  When considered from ancient African culture, the phrase it takes a village means that there is a community responsibility to connect together to safely raise a child (or resolve a crisis).   As a community of pain management professionals, we have a community responsibility to advocate for and provide safe and effective pain management.  When discussing her book, It Takes a Village, Hillary Clinton explained the phrase as “we are all in this together.”  The diverse group of SPS attendees and speakers personify the Clinton explanation.  Similarly, the term is also frequently used as a metaphor to describe the need for a variety of people to join together to  achieve an optimal outcome.  Those were the connotations that were originally sparked in me when reviewing our conference agenda.   As an organization we are a multidiscipline group working together to improve pain management for all patients with pain. 

Today, we are faced with enormous healthcare challenges and we know we need many clinicians from numerous disciplines to work together to resolve the issues generated by the opioid and pain crises.  It is clear that the best option available is utilizing a multidisciplinary multimodal approach of pain management.  Such an approach when utilized immediately following trauma and/or postoperatively will not only promote optimal safe resolution of acute pain situations but will also help avert the development of subsequent chronic  pain.  For those people who are living with chronic pain, intentionally utilizing a variety of pharmacologic and complementary interventions is the most effective approach to control pain and optimize function.

This year the  annual SPS Conference will begin with Blake Fagan, MD taking us through the history of the opioid crisis.  Along with other presenters he will then discuss safe pain management with controlled substances as well as non-opioid analgesic options.  Dan Doleys, PhD, will guide us in the importance of pre-opioid screening prior to starting opioid therapy. Our key note address will be presented by Steve Stanos, DO from Swedish Medical System in Seattle.  Utilizing the extensive knowledge, he has acquired through his amazing career in pain medicine and his participation on numerous national task forces, Dr. Stanos will bring us to the crossroads we now find pain management.  He will then offer innovative solutions for safe and comprehensive care.  Our own past president Mordi Potash, MD will enlighten us about utilizing psychopharmacology as a way to manage pain. 

This year several professionals will discuss how to help patients manage pain with non-medication options.  Non-opioid interventions, with a focus on neuropathic pain, will be discussed by Misha Backanja, MD.  From LSU, Ashley Mullens, PhD will give a lively overview of therapeutic cannabis.  Jennifer Murphy, PhD will explain what is involved with pain psychology and the use of the cognitive behavioral therapy methods in which she trains healthcare providers nationally.  Eric Royster, MD, a local New Orleans physician, will describe interventional options for managing pain.  Dr. Stanos will then discuss the value of functional restoration for chronic pain through the biopsychosocial model. Consistent with the importance of function,  the many pain management options available through physical therapy will be shared by Monique Serpas, DPT.

Cutting edge topics will be intertwined.  Ken Mautner, MD will present on the role of platelet-rich plasma and stem cell therapies as pain management for orthopedic conditions.  Then Forest Tennant, MD will share information on hormonal care as an intervention for chronic pain.  Our time will conclude with Charles Figley, PhD sharing his important work on how as clinicians we can help our patients most effectively by developing resilience to compassion fatigue within ourselves. 

Please join our “village” of pain management sages to support you and your local village of pain management caregivers.  Better yet, in the village spirit, consider bringing a colleague along to NOLA! You can return home as a team to invigorate and enlighten your own village of pain management professionals!   We look forward to seeing you in September!


Chou, R., Fanciullo, G. J., Fine, P. G., Adler, J. A., Ballantyne, J. C., Davies, P., … & Gilson, A. M. (2009). Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. The Journal of Pain, 10(2), 113-130.

Chou, R., Gordon, D. B., de Leon-Casasola, O. A., Rosenberg, J. M., Bickler, S., Brennan, T., … & Griffith, S. (2016). Management of Postoperative Pain: a clinical practice guideline from the American pain society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists’ committee on regional anesthesia, executive committee, and administrative council. The Journal of Pain, 17(2), 131-157.

Clinton, H. R. (2006). It takes a village.  Simon and Schuster.

Dowell, D., Haegerich, T. M., & Chou, R. (2016). CDC guideline for prescribing opioids for chronic pain—United States, 2016. Jama, 315(15), 1624-1645.

Gordon, D. B., de Leon-Casasola, O. A., Wu, C. L., Sluka, K. A., Brennan, T. J., & Chou, R. (2016). Research gaps in practice guidelines for acute postoperative pain management in adults: findings from a review of the evidence for an American Pain Society Clinical Practice Guideline. The Journal of Pain, 17(2), 158-166.

McAlindon, T. E., Bannuru, R., Sullivan, M. C., Arden, N. K., Berenbaum, F., Bierma-Zeinstra, S. M., … & Kwoh, K. (2014). OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis and cartilage, 22(3), 363-388.

Nuckols, T. K., Anderson, L., Popescu, I., Diamant, A. L., Doyle, B., Di Capua, P., & Chou, R. (2014). Opioid prescribing: a systematic review and critical appraisal of guidelines for chronic pain. Annals of internal medicine, 160(1), 38-47.

Urban Dictionary. (2019). It takes a village.

Self Compassion

Ann Quinlan-Colwell, PhD, APN

In this third of a series of writings about compassion and pain management, this article focuses on self-compassion.  The premise is that it is essential for health care providers to have compassion for self as the foundation to empathically and compassionately care for patients, while promoting compassionate satisfaction and preventing compassion fatigue.

Self-compassion is connecting care and support for self during times of personal suffering (Neff & Knox, 2017).  Since compassion is being aware of the pain of another person without judgment and a desire to alleviate pain, self compassion is focusing that non-judgmental perception to appreciate self pain with a desire to alleviate it (Veneziani, Fuochi, & Voci, 2017).   Germer (2009, p. 33-34) explains self-compassion as “simply giving the same kindness to ourselves (during suffering) that we would give to others.” 

Neff identified three essential components of self-compassion as being “self-kindness versus self-judgment, common humanity versus isolation, and mindfulness versus overidentification” (2016, p. 1).  Similarly, Reyes (2012) noted that being aware of other people, being kind to oneself (i.e. self-kindness) particularly when suffering, being mindful and being wise are attributes of self-compassion.   See table 1 for characteristics of self-kindness as described by Reyes.

Characteristics of Self-kindness (from Reves, D. 2012)

  • Treating self kindly when suffering
  • Replacing self-criticism with caring and understanding
  • Accepting own faults
  • Releasing regrets and disappointments
  • Giving up illusions about what might have been
  • Forgiving self
  • Accepting responsibility
  • Avoiding guild
  • Restraining from punishing self

Contrary to being selfish, compassion for self is essential for developing sincere compassion toward patients and others (Dalai Lama, 2003).  It is “a useful regulation strategy in which painful feelings are not avoided but are instead held in awareness with kindness, understanding, and a sense of shared humanity” (Costa & Pinto‐Gouveia, 2013, 1580).  Unlike narcissism, self-compassion is considered to be a healthy self-care element that is not associated with egotism,  enhancement of self-image or excessively positive self-evaluations (Veneziani, Fuochi, & Voci, 2017).  In fact, the authors of an interesting study reported that individuals with greater self-compassion had less acceptance of their own moral transgressions (Wang, Chen, Poon, Teng, & Jin, 2017).  

Although research of the concept is limited, self-compassion is associated with lower levels of anxiety and depression (Costa & Pinto‐Gouveia, 2013). Self-compassion is associated positively with health-related quality of life which was demonstrated among people living with multiple sclerosis (Nery-Hurwit, Yun, & Ebbeck, 2018). Conversely the absence of self-compassion is associated with unhealthy behaviors. Self-compassion is reported to be inversely correlated with disordered eating (Maraldo, Zhou, Dowling, & Vander Wal, 2016). The researchers of a recent study reported an inverse relationship between self-compassion and developing substance use disorder (Phelps, Paniagua, Willcockson, & Potter, 2018).

Consider the pain management clinical situation in which a clinician is working with a patient to manage pain with a multimodal approach using acetaminophen, gabapentinoids and opioids. The patient overdoses on the gabapentinoids and opioids in addition to some benzodiazepines received from another provider who also prescribed other opioids.  The pain management clinician who never developed self-compassion is devasted by the news and berates self for not checking the prescription drug monitoring database (PDMP).  The clinician does not forgive self and ruminates about this situation becoming increasingly depressed and anxious. Eventually this very talented and compassionate clinician leaves pain management entirely. 

The situation described could have a very different outcome if the clinician cultivated self-compassion.  With self-compassion the clinician could review the situation, acknowledge the omission of not checking the PDMP and grieve the patient.  Yet with self-compassion the clinician can experience remorse and regret while also knowing that there was no intent to harm the patient.  With self-compassion the clinician can understand that time constraints and a lack of appreciation for the importance of the PDMP information led to not checking. With self-compassion the clinician can forgive self and vow to assiduously check the PDMP whenever prescribing opioids, thus becoming a more responsible pain management clinician for thousands of patients. With an understanding and cultivation of self-compassion, this talented clinician is also able to be appropriately compassionate for people living in pain and guide patients toward self-compassion.        


Costa, J., & Pinto‐Gouveia, J. (2013). Experiential avoidance and self‐compassion in chronic pain. Journal of Applied Social Psychology, 43(8), 1578-1591.

Dalai Lama.  (2003). Transforming the Mind: Teachings on Generating Compassion.  London, Thorsons, Hammersmith.

Germer, C. (2009). The mindful path to self-compassion: Freeing yourself from destructive thoughts and emotions. Guilford Press.

Maraldo, T. M., Zhou, W., Dowling, J., & Vander Wal, J. S. (2016). Replication and extension of the dual pathway model of disordered eating: The role of fear of negative evaluation, suggestibility, rumination, and self-compassion. Eating Behaviors, 23, 187-194.

Neff, K. (2016). Self-compassion. Mindfulness in Positive Psychology: The Science of Meditation and Wellbeing, Encyclopedia of Personality and Individual Differences. 37, 1-8.

Neff, K. D., & Knox, M. C. (2017). Self-compassion. V. Zeigler-Hill, TK Shackelford (eds.), Encyclopedia of Personality and Individual Differences, 1–8. DOI 10.1007/978-3-319-28099-8_1159-1.

Nery-Hurwit, M., Yun, J., & Ebbeck, V. (2018). Examining the roles of self-compassion and resilience on health-related quality of life for individuals with Multiple Sclerosis. Disability and Health Journal, 11(2), 256-261.

Phelps, C. L., Paniagua, S. M., Willcockson, I. U., & Potter, J. S. (2018). The relationship between self-compassion and the risk for substance use disorder. Drug and Alcohol Dependence, 183, 78-81.

Reyes, D. (2012). Self-compassion: A concept analysis. Journal of Holistic Nursing, 30(2), 81-89.

Veneziani, C. A., Fuochi, G., & Voci, A. (2017). Self-compassion as a healthy attitude toward the self: Factorial and construct validity in an Italian sample. Personality and Individual Differences, 119, 60-68.

Wang, X., Chen, Z., Poon, K. T., Teng, F., & Jin, S. (2017). Self-compassion decreases acceptance of own immoral behaviors. Personality and Individual Differences, 106, 329-333.

Chronic Migraine: 6 Months of Therapy with Erenumab (Aimovig)

Lawrence Robbins, M.D.

NOTE: This is a shortened version of an article published in the March issue of Practical Pain Management (available online).

Migraine is a relatively common illness, affecting 12% of the population. Chronic migraine (CM) is a frequently encountered subset of migraine, and presents certain difficulties in treatment. Those with CM have at least 15 headache days per month, with at least 8 days being migrainous in nature. In addition, medication overuse headache cannot be a major contributing factor to the headache pattern.  Many with CM do not do well with the usual preventive approaches, and suffer from refractory chronic migraine (RCM).  Patients with RCM have failed on at least 3 types of preventive medications. A number of our usual migraine preventive approaches have limited efficacy, and side effects often limit use. Additionally, effectiveness often diminishes over time. New preventive approaches are needed for chronic migraineurs.     

Calcitonin gene-related peptide (CGRP) is an important neuropeptide involved in the migraine process. CGRP receptors are ubiquitous in the sites that are involved in migraine pathogenesis. CGRP is involved in mast cell degranulation, neurogenic inflammation, and the subsequent vasodilation. During a migraine, CGRP levels usually rise.  For those with migraine, infusions of CGRP may precipitate an attack. During a migraine, trigeminal nerves that are activated may release CGRP, as well as other inflammatory compounds. The monoclonal antibodies (mAbs) that inhibit CGRP have been effective for a number of patients with chronic migraine.

Our current oral migraine preventives include antidepressants, anticonvulsants, and medications used for hypertension. These have limited efficacy, and often are not tolerated. Onabotulinumtoxin A is more effective than the oral preventives, and has few side effects. For those with chronic migraine, there is a need for more effective preventives. The CGRP monoclonal antibodies that may help to fill that role.

Erenumab-aooe (referred to as erenumab in this article), was the first CGRP mAb to become commercially available, in May of 2018. Erenumab is a subcutaneously administered once-per-month injection. There are currently 2 other mAbs available: fremanezumab and galcanezumab.  These are all large molecule mAbs, with little penetration through the blood brain barrier. Erenumab targets the CGRP receptor, while the others in this class affect the CGRP ligand. These large molecule mAbs have several major advantages, including little or no drug interactions. In addition, they are cleared through the reticuloendothelial system, and do not irritate the liver or kidneys. Demand for these newer preventives has been brisk, as there has been a paucity of effective therapies for those with chronic migraine. 

We evaluated the results of erenumab after the first 6 months of treatment. The first study involved 220 consecutive chronic migraine (CM)patients, after 3 months of therapy. 43% of all patients experienced 0 to 30% relief. 34% reported 30 to 70% relief, while 24% described 70 to 100% relief.  Among the 43% with only 0 to 30% relief, many did choose to continue with erenumab. Many of these patients did state that they were satisfied with 15 to 30% relief. Forty-eight patients dropped off of the erenumab after months 1 or 2.  Ten percent of patients reported almost complete (95 to 100%) relief over the 3 months. The patients in this study were relatively more refractory than those in the Phase 3 erenumab studies. These patients had all utilized at least 3 preventives, and almost all had tried onabotulinumtoxin A.  One hundred thirty-two of the patients were considered to have refractory chronic migraine.  In this study, the efficacy of erenumab was reasonable, even considering the relatively refractory population. We do not know how efficacy will hold up over time.

There were a considerable number of side effects reported by the 220 patients. Constipation was the most prevalent, at 20%.  The constipation was severe in some patients, requiring treatment. At least 4 patients discontinued the erenumab primarily due to constipation. Nausea (7%) was also described, as was an increased headache (5%). The nausea usually resolved, but with an increase in headaches, the erenumab was usually discontinued. Fatigue (5%) was sometimes severe, requiring discontinuation of the medication. Joint pain (3%) sometimes accompanied the severe fatigue.

Depression (3%) was sometimes exacerbated after erenumab was started. Anxiety (2%) also occurred was described. Diarrhea was seen in 2% of patients, and several patients experienced severe diarrhea. Injection site reactions (2%) were mild, not requiring discontinuation.

We observed 3 serious side effects. One 21-year-old had a probable migraine-related stroke. Her cognitive symptoms have improved, but she is left with mild to moderate dysgraphia. She had a history of hemiplegic migraine (although none for 3 years), and had been using erenumab for 4 months. She was also on a low dose birth control pill that contained estrogen.   The second patient is a 31-year-old with severe neurologic symptoms, which began 2 weeks after her 2nd erenumab injection. She also suffered from severe fatigue, with joint pains. Symptoms did eventually resolve (but they recurred 3 months later, off of the medication). The third patient suffered severe fatigue and joint pain 3 weeks after receiving the erenumab. She had a history of rheumatoid arthritis, which had been in remission. She eventually improved with corticosteroid therapy.   The erenumab was probably a factor in these serious side effects. Serious side effects are a major concern with these CGRP monoclonal antibodies.

 The second study evaluated 26 poor responders (0 to 15% relief) versus 26 patients with an excellent outcome (70 to 100% relief). Both of these groups consisted of relatively refractory patients, with a history of headaches that averaged 28 years. The location of headaches for both groups was primarily both anterior and posterior. Sixteen of the 26 in the poor response group reported neck pain, and 10 in the excellent group. Central sensitization syndromes were more commonly encountered in the excellent group (11 vs. 5 patients). Most patients suffered from anxiety. Depression (15 in the poor group, 17 in the excellent group) was frequently encountered, although less than anxiety. Insomnia was commonly encountered as well. Sixteen of the poor response group was considered to have refractory chronic migraine, while only 7 in the excellent group had been diagnosed with RCM. The poor response group was more likely to have moderate (6 vs. 2) or severe refractory chronic migraine (6 vs. 1) than in the excellent response group. This author has published on separating RCM into mild, moderate, and severe. We used a 10-point scale to determine the level of refractoriness. It may be clinically useful to separate refractory patients into these different levels. All of these patients had tried onabotulinumtoxin A therapy. Eight of the poor group had responded well, while 12 in the excellent group did well with onabotulinumtoxin A. A number of the patients continued with onabotulinumtoxin A, along with the erenumab.  The majority of patients had a positive response to triptans. In the poor response group, 18 had good responses to opioids, while only 8 of the excellent group responded to opioids. A number of the patients had responded well to butalbital compounds (12 and 10 patients).

The third study evaluated those 50 patients who had completed 6 months of therapy. The average relief started with 36% and 35% for the initial 2 months, but slowly declined to 27% by the end of the 6th month. Patients who averaged 0 to 15% relief for the first 2 months were assessed. They continued to do poorly, with 13/15 patients experiencing 0% to 15% after 6 months. Only one patient improved significantly over time.  Similarly, most of the patients(N=9) who did very well (70% to 100% relief) for the first 2 months generally continued to have success. After 6 months, 6 of these 9 patients maintained the excellent relief.

The 2 main issues with CGRP mAbs for migraine prevention are: 1. will these remain reasonably effective over time, and 2. what is the true side effect profile. The efficacy question will only be answered after several more years of treatment. Regarding side effects, this author has major concerns about the various risks that could arise due to blocking of CGRP on a chronic basis. The following are some concerns.

CGRP most likely is an inhibitor of platelet aggregation. Blocking this effect may increase the chance for cardiac or cerebrovascular effects. As of Sept. 30th, 2018, there were at least 6 cerebrovascular events listed on the FDA site.  This author has put in a Freedom of Information Request for details on those events.  This author has heard about several other erenumab-related strokes, yet to be officially reported, in addition to the one reported in this study.

 CGRP plays some role in the prevention of hypertension, and may be somewhat protective for cardiovascular disease. CGRP is a powerful vasodilator, particularly in the meningeal and cerebral arteries. Blocking CGRP may lead, under certain circumstances, to intracerebral vasoconstriction.  It is possible that other related compounds, such as amylin or adrenomedullin, may help compensate for the loss of CGRP. In addition, various vasodilators may also help to mitigate negative effects from CGRP antagonism. These include nitrous oxide, vasoactive intestinal peptide, and others.  CGRP also is important in neovascularization.  CGRP enhances recovery from ischemia by stimulating angiogenesis. CGRP helps to prevent secondary lymph edema, and enhances lymphangiogenesis. The adverse health consequences on the above systems, by blocking CGRP, are unknown.

The effects of CGRP mAbs on hormones has not been studied. The hypothalamus and pituitary are not, for the most part, protected by the blood brain barrier (BBB). CGRP is present in these areas. In theory, CGRP antagonism could result in various hormonal effects. The choroid plexus, involved in CSF production, also is not protected by the BBB. In addition, the area postrema, involved in nausea and vomiting, is not protected by the BBB.  Circumventricular organs, important in homeostasis of various functions, are also not protected. Studies have yet to be done regarding the effects of CGRP mAbs on these areas.

 CGRP is involved with skin blushing, flushing, cold sensitivity, itch, edema, and thermoregulation. After surgery, or after a serious burn, healing may be impaired by the CGRP mAbs. CGRP does play a role in the metabolism of bone, and is involved with bone healing. In diabetics, by antagonizing CGRP, there may be a higher risk for coronary artery disease. In the GI tract, CGRP has myriad functions. CGRP is involved in motility, and in protecting the gastric mucosa. Constipation may occur with CGRP antagonism, and to a lesser degree, diarrhea. None of the above effects have been studied, with regard to the CGRP mAbs.

We do not want to use these medications during pregnancy. There may be more risk to the CGRP mAbs in later stages of pregnancy. Preliminary studies in animals have not revealed major issues with the newborn animal.

 A number of patients have reported severe fatigue from erenumab.  Additionally, joint pain has been an issue for some patients. It is possible that the hypothalamic-pituitary-adrenal (HPA) axis may be involved with these side effects, as the HPA axis is not protected by the BBB. There have been no studies of CGRP mAbs and the HPA axis.

As of December 31, 2018, 7300+ possible side effects had been reported to the FDA; over 800 were deemed serious.  Only a fraction of side effects are officially reported to the FDA. It is very concerning that we have a paucity of studies on the serious consequences of blocking CGRP for long periods of time. 

Until we know more, it is prudent to screen patients for risk. Informed consent should be obtained. Patients at increased risk may include those with risk factors for stroke, including the usual risk factors (lipids, HTN, diabetes, family history, cigarettes). In addition, at higher risk may be patients with clotting abnormalities, positive lupus anticoagulant, or positive anticardiolipin antibodies. It is possible that hemiplegic migraine, or those with frequent auras, may represent an increased risk as well. Certain birth control pills may be a problem, although this is controversial. Patients with recent surgery, or who have suffered a recent fractured bone, should possibly delay the use of the CGRP mAbs. Those with active GI ulcers, or with inflammatory disease of the GI tract, may also be at an increased risk. Because of the possible hypothalamic and pituitary effects, patients with various hormonal issues may be affected.  The effects on bone growth, as well as on hormones, cautions against using these treatments in children and adolescents.  We need studies in all of these areas.

There are major limitations to this study. It is retrospective, and studies #2 and #3 had limited numbers of patients. The patients are relatively refractory, as compared to most migraineurs. We relied on diaries and calendars, as well as patients’ self-reported histories. These are not always accurate. Most, but not all, of the patients maintained calendars of their migraine days. We were not able to ascertain whether each of the reported side effects was due to the erenumab. This is basically an observational study, with no control group.

The major strength of this study is that the patients were not selected for any purpose other than migraine treatment. They represented a “real life” group of migraineurs, albeit relatively refractory. We also were able to tease out and complete an analysis of poor responders vs. excellent responders. The 6- month results may be helpful in understanding efficacy over longer periods of time.

References/ For Further Reading

  1. Lassen LH, Haderslev PA, et al. CGRP may play a causative role in migraine. Cephalalgia 2002; 22:54-61
  2. Tepper, S. Anti-Calcitonin Gene-Related Peptide (CGRP) Therapies: Update on a previous review after the American Headache Society 60th Scientific Meeting, San Francisco, June 2018. Headache 2018; 58:276-290
  3. Reuter U. Anti-CGRP antibodies: a new approach to migraine prevention. Lancet Neurol. 2014; 13(9):857-859
  4. Tepper SJ, Ashina M, Reuter U, et al. Safety and efficacy of erenumab for preventive treatment of chronic migraine: A randomized, double-blind, placebo-controlled phase 2 trial. Lancet Neurol 2017; 16: 425-434.
  5. Goadsby PJ, Reuter, U, et al. A controlled trial of erenumab for episodic migraine N Engl J Med 2017; 377:2123-2132
  6. Dodick DW, Ashina M, et al. ARISE: A Phase 3 randomized trial of erenumab for episodic migraine. Cephalalgia 2018; January ( ahead of print)
  7. Reuter U, Goadsby PJ, et al. Efficacy and safety of erenumab in episodic migraine patients with 2-4 prior preventive treatment failures: Results from the Phase 3b LIBERTY study. Emerging science platform presentation and poster 009. American Academy of Neurology meeting, Los Angeles, April 24, 2018(abstract).
  8. Depre C, Antalik L, et al. A randomized, double-blind, placebo-controlled study to evaluate the effect of erenumab on exercise time during a treadmill test in patients with stable angina. PO-01-198. Cephalalgia 2017; 37(Supplement 1):340-341.
  9. Tepper SJ, Pascual J, et al. Analysis of blood pressure following short-term and long-term treatment with erenumab. Poster 105. 68th American Academy of Neurology meeting, Los Angeles, CA, April 25, 2018(abstract)
  10. Headache classification committee of the international headache society (HIS). The international classification of headache disorders, 3rd edition (beta version). Cephalalgia 2013.
  11. Refractory chronic migraine: a consensus statement on clinical definition from the European Headache Federation. J Headache Pain 2014; 15:47.
  12. American Psychiatric Association (2013). Diagnostic and statistical manual of mental disorders (5th edition), Washington, D.C.
  13. Robbins, L Refractory chronic migraine: long-term follow-up using a refractory rating scale. J Headache Pain 2012; 13:225-229.
  14. Matsumato Y, Ueda S, et al. CGRP inhibits human platelet aggregation. Japan Circulation J 1996;60(10):797-804.
  15. FDA Medwatch adverse drug site:  (erenumab aooe).
  16. Russell, FA, King, R et al. Calcitonin Gene-Related Peptide: physiology and pathophysiology Physiol Rev 2014;94:1099-1142.
  17. Majima, M, Ito, Y, et al. CGRP/CGRP receptor antibodies: potential adverse effects due to blockade of neovascularization Trends in Pharmacological Sciences 2018 (e published)
  18. Brain S, Grant A Vascular actions of Calcitonin Gene-Related Peptide and Adrenomedullin Physiol Rev 2004;84:903-934
  19. Deen M, Correnti E, Kamm K, et al. Blocking CGRP in migraine patients-a review of pros and cons. J Headache and Pain 2017;18(1):96.
  20. Gangula PR, Zhao, et al. Pregnancy and steroid hormones enhance the vasodilation responses to CGRP in rats. Am J of Physiol Heart Circ Physiol 1999;276:H284-H288.