Not sure where to post this, but I'm getting worse with this problem. I get severe low back pain after standing or walking. It's been like this for a few years, but lately, I can't stand more than a couple minutes without feeling the need to bend forward to alleviate the pressure on my back. I've mentioned it to my doctor and my chiropractor and both of them just sort of blow it off as nothing - but it's seriously affecting my quality of life. Even grocery shopping is difficult anymore. I have similar pain cause by standing and any type of movement. I would check to see a specialist who knows about SI dysfunction first.

The best way to tackle chronic pain, is to better understand what changes have happened with the brain through a Functional Neurological assessment, and apply a tailored brain-based therapy. Explain Pain by David Butler and Dr. Lorimer Moseley is an evidence based. Because the actual content of the book is absolutely worth five stars. 10 minutes without neck and head pain, now I can run for 20 minutes.

This may not be the root of the problem but the SI dysfunction will cause low back pain. I had this for a couple of years and blew it off and then the pain became severe and has spread throughout my hip area. I recently found out that I have misformed hips and this has caused degeneration of my hips and tendons surrounding my hips. If I had gotten the diagnoses a couple of years ago I may not be in such pain right now. I would see if you can get xrays and an MRI to rule out vertebra problems. At 20 years of age,back in the 1990's.

Hi you have ces which is a narrowing of the spinal cord. Your disc or material will have gone central and put pressure of your cord which results in nerve damage. Decompression surgery should be done Asap. I know this because it happened to me.

It can cause major bowel and bladder problems and sexual problems. But the worst you could lose the power and the feeling in your legs. So please get it checked out I was showing red flag warning signs for years. Don't end up like me make sure they listen to you. Unfortunately doctors think back pain is unimportant.

Hope it's not too late. Hiya, I know this Is years after you posted about your lower back pain,I was hopeing that you still come on here.I have the exact same problem as you had & I have m.s as well,I jist wondered what the outcome of It all was?? I have never suffered so much pain, & like you the smallest of tasks I have to sit down to relieve the pain.This Is a long shot I know because It was so many years ago you posted,I just really hope that you read this.I'm going to the doctors on Tuesday to ask for a mri,already been once but It was not my Doctor so he told me to up my morphine.Which done no good so stopped taking It. If there Is anyone else on here with m.s & has or Is suffering with the same sort of pain, could you please reply to me as I'm going out of my mind thinking all sorts lol Thankyou anyone that has read this, Loulou53. HI.this is 4 years later, but my back has been bothering me for years.I had an MRI and it showed that I have a herniated disk. I can't walk tor stand but for a few minutes and my back starts hurting me soooo bad.I mean excruciating pain.I have to either lean forward on something, or sit down to take the pressure off.

It kinda feels like Im being shocked. It hurt so bad that it literally takes my breath away.NOW THATS BAD!!.IDK.all I know is it hurts like hell.

I can't work. At 47 Im having to live at my dads and that is embarrassing. He said I could stay as long as I needed but still. I don't have small kids. My daughter is 24, and lives on her on, so its not like I have any small kids running around hollering.THANK GOD FOR THAT.HA HA HA Anyway.I have a neurosurgeon appointment September 21st 2016 Im hoping and praying that he can tell me whats wrong, and hopefully fix it.

I have had the same symptoms. I hurt so bad.

I couldn't sit long, walk very far of stand very long. When standing and then siting down I have a sharp spasm that lasts about 30 seconds. I went through many tests.

MRI, CT scan, x-rays. They did find something with my lower back. Calcium deposits, artheritis. They called it Sciatica. The only thing that helps me some is doing stretches.

It dosn't take all the pain away but it does ease it. I am able to walk more, stand longer and sit longer. Everytime it really starts to hurt I stretch my lower back.

I also do a couple of yoga stretches. I hope this helps. They also gave me a cortisone shot in my spine. It worked for a while. I find stretching works just as well. This sounds like SJD or sacroiliac joint dysfunction.

A diagnosis is fairly easy in much of the Western world but not here in USA. It is diagnosed best by use of a sacroiliac injection of a lidocaine solution. The shot is given and after upon standing you should feel 75% to 100% relief. That would be a positive test that you have a dysfunction. Then another shot is given of a steroid like Kenalog into the sacral cavity on the side affected. Usually it is one side but sometimes both.

The doctor should then send you to a chiropractor with a few days of injection so he can manipulate joint. You will be a new person after this.

I suffered for 8 yrs with this. The symptoms are identical to yours.

I had X-rays and MRI's and nothing was found. I had to tell them to do this and they referred me to a place that did it on an outpatient basis. You really need to talk to your doctor about it as they never seem to identify this as a SJD. Get another DR.

If you have to but the chances are very high this is your problem. I understand the feeling your going through.

I too am having the same problems. I have been in the nursing field for 13 years and never had so much pain in my lower back like this. I'm only 33, and have to lean on Walls if I'm standing for over 2 minutes. I can't walk to my car in my parking lot without my low back and hips feeling like their going to give up on me. I haven't got a MRI or XRAY yet due to me gaining weight for sitting all the time.

Doctors are going to say its my weight. But I can't work out like I use to because of the pain. I cry almost everyday because I can't find out what it is. I told doctors about it but they just blow it off. This developed and got worst with in 3 months, and three months I been out of work.

I want to go back to work but can't walk or stand without me leaning or finding support to ease pressure off my lower back and hips. I could only pray we all could find someone that could give us the answer. Glad I found this thread I was beginning to think I was going mad. I have suffered acute pack pain since I was 29.

It started literally over night - I woke up unable to lift my head from the pillow moving at all was agony. In the beginning docs said it was muscle strain,but several years and many tests later I was told it was scoliosis & I would just have to live with it & I have struggled on since. From being active I went to being hardly able to move. Things have got really bad in the last year - standing just 2 mins in the same position results in acute pain across my lower back back centering on hip area. Doctors blame sciatica but after 20+ years of that pain I can tell the difference losing weight is impossible when you can not move.If anyone gets a 'proper' diagnosis I would love to hear from them. I feel like I am reading myself.

I have the same problems with my back. I am unable to stand or walk for no more than a minute or two. I have been diagnosed with Degenerative Disc Disease & Osteoarthritis.

I have 2 discs in my back that are completely dried out. Absolutely no fluid. So it is just vertebrae on vertebrae. Because of my weight i feel like my dr's wont help me. But please tell me if I am in constant ppain and unable to get around how am i suppose to lose weight?? One dr even told me it is useless for me to be on a diet. Code::blocks online. WOW Thanks for the support.

The drs wont even give me pain meds. All they give me is Mobic & Naproxen. Absolutely no help at all. My quality of life is so deminished I want to give up. I have to sit to do dishes or take a shower or anything in general.

BY THE WAY I AM ONLY 34 YEARS OLD. I have been dealing with this since i was 30.:(. I'm 17 and I've had this same exact issue. Only it takes me about 30 seconds to a minute before it starts hurting, and it hurts worse the more I continue to stand. It only hurts on the right side of my lower back. It kinda sends the throbbing pain down my leg too.

Its unbearable and crippling. The only relief I find is when I'm sitting or hunched forward. Only been feeling it for about a week now, but I've had no prior injuries to my back, so I can't understand what could be causing this. I felt like I could have written your story myself.

I am 44 years old and my pain has been going on for 3 years now. The past 10 months it has gotten to where I cannot even stand to take a shower. My husband has to help me get dressed, because I cannot stand in one spot for too long. I have went through 4 doctors and 3 MRIs and X-rays and they all try telling me it is arthritis. I have sent my results from my MRI out of state to a doctor that has never met me, and he found I have degenerative disc disease, a bulging disc, a cyst on my kidneys(5cm), spurs and bone fragments, along with some other issues.

He suggested that when I walk and stand for even a minute, that my kidneys are stretching and pushing my disc causing my pain to start and increase rapidly to where I cannot move anymore. At my insistence, I have an appt with an orthopedic surgeon next week to discuss FIXING the problem, instead of blowing me off and trying to mask it with pain killers and muscle relaxers. They do not even affect the pain, and physical therapy just made it worse.

I have gained 130 pounds since this started as I cannot move around anymore. I used to walk almost 2 hours a day, and run and play with my kids. Now I am 80% bed-bound.

This is NOT NORMAL in any way, and if any doctor tries to tell you that it is, get another one.and another.until one actually listens to you. My heart goes out to all of you with this type of back pain. Real quick, here is what I went through. In my early 30's I started having severe lower back pain whenever I was on my feet for more than 15 minutes. I called it a 'belt of pain' because I also felt it in my pelvis. When I mentioned it to drs., I was sent for tests to see if I had ovarian cysts, endometriosis, etc.

Nothing found. I couldn't understand why 85 year old women were able to stand in line at the grocery store and I was in such pain! Now, at age 57, I finally went to the dr. And was diagnosed with significant degenerative disc disease and spinal arthritis. I used to think this was 'all in my head.' Pursue this for a diagnosis.

When I was younger, no one took me seriously. Once you're over 50, it can be different. All those years! I'm doing ok; taking 2 Aleve daily and being careful. Again, my heart goes out to you.

BrokenMama you are too young to have so much pain. Babyjessie is correct.this is not normal. Don't stop until you find a compassionate dr. And get some help. Check out Piriformis Syndrome. The piriformis can put pressure on the sciatic nerve and cause hip/back/leg problems. It's tough to heal it but not impossible.

Sedentary lifestyle (sitting all day at the computer, etc.), gaining weight in the abdominal area and losing core strength all contribute to making the back pain worse. It's all about muscle balancing. When something is out of whack, it throws other things out of whack until the body can't take it any more. Piriformis syndrome is often missed by doctors as it won't show up in an MRI or X-ray.

Yoga and stretching, along with PT usually help, but it does take awhile and you have to be consistent in doing the stretching and exercises everyday, as well as being conscious of your body mechanics. Rick Olderman is a PT who's written a number of books on fixing pain. Check out his 'Fixing You' series. I have the one on Hip and Knee Pain and it's very informative.

Will be purchasing the one on Back Pain next. The Content on this Site is presented in a summary fashion, and is intended to be used for educational and entertainment purposes only. It is not intended to be and should not be interpreted as medical advice or a diagnosis of any health or fitness problem, condition or disease; or a recommendation for a specific test, doctor, care provider, procedure, treatment plan, product, or course of action. MedHelp is not a medical or healthcare provider and your use of this Site does not create a doctor / patient relationship. We disclaim all responsibility for the professional qualifications and licensing of, and services provided by, any physician or other health providers posting on or otherwise referred to on this Site and/or any Third Party Site. Never disregard the medical advice of your physician or health professional, or delay in seeking such advice, because of something you read on this Site.

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Abstract

Background

Nausea is a common and disabling symptom of migraine. The origin of nausea is not well understood although functional connections between trigeminal neurons and the nucleus tractus solitarius may explain occurrence of nausea with pain. However, nausea occurs as a premonitory symptom in about a quarter of patients, suggesting that a primary brain alteration unrelated to the experience of pain may be the reason for nausea.

Methods

We performed positron emission tomography scans with H₂¹⁵O PET in premonitory phase of nitroglycerin-induced migraine and compared patients with and without nausea.

Results

The results showed activation in rostral dorsal medulla and periaqueductal grey (PAG) in the nausea group, which was absent in the no nausea group. The rostral dorsal medullary area included the nucleus tractus solitarius, dorsal motor nucleus of the vagus nerve and the nucleus ambiguus, all of which are thought to be involved in brain circuits mediating nausea.

Conclusions

The results demonstrate that nausea can occur as a premonitory symptom in migraine, independent of pain and trigeminal activation. This is associated with activation of brain structures known to be involved in nausea. We conclude that nausea is a centrally driven symptom in migraine.

Background

Nausea is a common and disabling symptom of migraine, which is listed in the International Classification of Headache Disorders-III-beta (ICHD-III-beta) as a key symptom of an attack []. The neurobiology of nausea in migraine is not well understood. Nausea is often associated with the pain in migraine and in this regard, connections between trigeminal neurons and nucleus tractus solitarius (NTS) are thought to explain the occurrence of nausea with headache []. However, nausea can already be present in the premonitory phase, before the appearance of headache.

In a previous study, nausea in the premonitory phase correctly predicted headache in a quarter of migraineurs []. The presence of nausea before pain suggests it can occur independent of pain. Premonitory symptoms represent the earliest clinical change in migraineurs. Premonitory symptoms, such as tiredness, difficulty in concentration, mood changes, yawning and cravings, suggest the origin of the problem is likely to be within the brain, and therefore, nausea could also be a predominantly centrally driven symptom. We hypothesized that central brain structures involved in nausea and emesis, in particular, the NTS, is activated in migraine patients who experience nausea in the absence of pain in the premonitory phase. We conducted positron emission tomography (PET) scans as a marker of neuronal activity in the premonitory phase of migraine to be able to compare patients with and without nausea.

Methods

Patients included in this study were screened for an over-arching investigation of the premonitory phase of GTN-induced migraine []. After completion of PET scans, a pre-planned sub-group analysis was conducted between patients with and without nausea in the premonitory phase.

Recruitment

We conducted telephone interviews, after advertisements in local media, to select patients who met the inclusion criteria: age 18–65 years, migraine without aura [], less than fifteen days of headache a month, premonitory symptoms before headache [], no major medical conditions and not on preventive drugs for migraine or any other regular medications, which could confound the study. We excluded patients with migraine aura to prevent confusion with premonitory symptoms, as both usually occur before headache. The study was approved by the UCSF Committee on Human Research and the Radiation Safety Committee. Written informed consent was obtained from all patients before study inclusion.

Screening

We initially screened one-hundred and twenty-five patients. Twenty-seven satisfied the inclusion criteria and agreed to participate. The most common reasons for non-inclusion were: headache for more than fifteen days a month (n = 45), confounding medications (n = 29), migraine aura (n = 12), and patients unwilling due to radiation risk (n = 8); less common reasons for exclusion are included in a table (Table 1).

Table 1

Miscellaneous reasons for non-inclusion after telephonic screening

GTN triggering

These twenty-seven patients were invited for the first visit during which we infused intravenous GTN 0.5 micrograms × kg^-1 × minute^-1 over 20 minutes to select patients who responded with premonitory symptoms followed by a delayed headache resembling their migraine headache, hereafter referred to as migraine headache []. Details about headache and associated symptoms were asked initially every five minutes and then less frequently (Table 2). Blood pressure, oxygen saturation and pulse rate were recorded initially every five minutes and then less frequently. Of these twenty-seven patients, eighteen had migraine headache. Out of these eighteen, thirteen patients had premonitory symptoms before migraine headache. These thirteen patients were invited for PET scans at least seven days after the first GTN infusion.

Table 2

Recording of symptoms was continued at 10–15 minute intervals until all scans were complete.

PET scanning

All patients had been pain free at least 72 hours before the PET scans. The procedure for GTN infusion and recording of symptoms was repeated as on the first occasion. We performed PET scans with the GE Discovery VCT PET/CT system (Waukesha, WI, United States) in three-dimensional mode with septa retracted. All subjects were instructed to keep their eyes closed during the scans. The subjects were positioned in the PET scanner, and their head immobilized with standard immobilization straps and a low dose CT scan was performed for attenuation correction. CT scans for attenuation correction were repeated when patients exited the scanner for relaxation between conditions. An antecubital vein cannula was used to administer the tracer, 370 MBq of H₂¹⁵O, which was repeated before each scan. The activity was infused into subjects over twenty seconds at a rate of 10 ml/min. The interval between scans was at least ten minutes allowing an interval of five half-lives of H₂¹⁵O (t_1/2 = 122 seconds). The PET data were acquired dynamically and summed for one 90-second frame beginning five seconds before the peak of the head curve.

Scans

Each patient had scans in three conditions – baseline (pain free), premonitory phase (pain free) and migraine headache. We could not randomize the order of the scans since the premonitory and migraine headache phases were triggered by the GTN infusion sequentially. We planned to do three scans in each condition. However, the number of scans in the premonitory phase depended on how soon the migraine headache developed. Soon after the initiation of GTN, patients had a mild headache that lasted for a mean of 23 ± 7 minutes (range 11–32). Premonitory scans were performed after the GTN headache had completely subsided, premonitory symptoms were present and the migraine headache had not appeared. The mean time for the first premonitory scan after initiation of GTN infusion was 56 ± 16 minutes (range 38–80). Migraine scans were performed when the migraine headache (delayed headache) was moderate or severe. The mean time for the first migraine scan after initiation of GTN infusion was 125 ± 41 minutes (range 89–225). Subsequent scans in the premonitory and migraine phases were conducted at approximately 10 minute intervals. Out of thirteen, ten patients had at least one scan during the premonitory period when no pain was present. Therefore, only these ten patients’ scans were used for the final analysis.

All the ten patients had three scans each during baseline. In the premonitory phase, five patients had two scans each, three patients had one scan each; one patient had three and one patient had four scans. In the migraine headache phase, five patients had three scans each, two patients had two, one patient had one, one patient had four and one patient had five scans. Images were reconstructed by 3D iterative reconstruction (3DIR) provided by the manufacturer into 47 image planes (separation 3.27 mm) and into a 128 × 128 pixel image matrix (pixel size 2.1 × 2.1 mm²).

Statistical analysis

SPM2 (http://www.fil.ion.ucl.ac.uk/spm) was used for data preprocessing and statistical analysis []. Images were realigned with the first as reference and stereotactically normalized into MNI space. The normalized images were smoothed with a Gaussian filter of 8 mm full width at half-maximum. Statistical parametric maps were derived with pre-specified contrasts, comparing rCBF (Regional Cerebral Blood Fow) during states of interest. Using the brainstem as the region of interest (ROI), we specifically looked for differences in the two groups: nausea and no nausea in the premonitory phase, in areas known to be involved in nausea like the rostral dorsal medulla containing the NTS, dorsal motor nucleus of the vagus nerve, nucleus ambiguus and area postrema [-]. Since there are no known MNI coordinates representing these areas, we used the human atlas by DeArmond [11] to approximate the location of activations. We initially carried out a paired t-test to study activations in the premonitory phase > baseline, in the nausea group, and then carried out the same procedure separately for the no-nausea group. Finally, we used a two sample t-test to study activations in the premonitory phase > baseline, in the nausea group > no nausea group. As we had a strong hypothesis regarding activations in the lower brainstem in the nuclei noted above, we initially looked at the results with a threshold p < 0.05, uncorrected for multiple comparisons. Activated clusters in the above-mentioned areas were selected. We then carried out a small volume correction (SVC) for multiple comparisons within a sphere of radius 5 mm, centered at co-ordinates representing maxima within this cluster. P < 0.05 after false discovery rate (FDR) correction for multiple comparisons was deemed significant.

Results

The premonitory symptoms in the two groups during the scanning session are listed in Table 3.

Table 3

Premonitory symptoms in GTN-induced migraine during the scanning session

Three patients had nausea and seven did not have nausea in the premonitory phase during the scanning session. The age range was 19–47 years (32 ± 10, mean ± SD). Patients in the two groups did not differ in age (unpaired tailed t-test, p = 0.6). There were two males in the nausea group and one male in the no nausea group.

Comparing the premonitory scans > baseline scans in the nausea group with an uncorrected p value threshold of p < 0.05, we found brainstem activations in the rostral dorsal medulla and the PAG. These results survived SVC for multiple comparisons within a sphere of radius 5 mm centered at co-ordinates representing maxima within that cluster. Comparing the premonitory scans > baseline scans in the no-nausea group with an uncorrected threshold of p < .05, we did not find activations in the brainstem. Finally, comparing the premonitory scans > baseline scans, in the nausea group > no-nausea group with an uncorrected threshold of p < 0.05, we again found activations in the dorsal rostral medulla and the PAG, which survived SVC for multiple comparisons within a sphere radius of 5 mm centered at co-ordinates representing maxima within that cluster (Figure 1 and Table 4). Referring to the atlas by DeArmond [11], the activations in the rostral medulla coincided with the NTS, dorsal motor nucleus of the vagus nerve and nucleus ambiguus.

Areas of increased rCBF in the premonitory phase of migraine in patients with nausea > patients without nausea. Areas of increased rCBF in the premonitory phase > baseline are depicted in patients with nausea > patients without nausea. The results are superimposed on an anatomical reference derived from a representative T1-weighted MRI of one of the patients in this study. The colour bar indicates the colour coding for the Z scores. Images are displayed in radiological convention i.e. left side of image is right side of brain. A threshold of p < 0.01, uncorrected, was used for display purposes.

Table 4

MNI co-ordinates and statistical values of a priori areas with increased rCBF in the premonitory phase as compared to baseline in patients with nausea more than patients without nausea

The co-ordinates represent the maxima within an activation cluster.

*after SVC for multiple comparisons using false detection rate (FDR) within a sphere of radius 5 mm centered at the given co-ordinates.

Discussion

Our findings link nausea in the premonitory phase of migraine to activation of central structures in the rostral dorsal medulla and the PAG. The activation in the rostral dorsal medulla included the NTS, dorsal motor nucleus of vagus and nucleus ambiguus, all of which are known to be important central mediators of nausea. Primary activation of these nuclei exclusively in patients who experience nausea before the appearance of headache and trigeminal activation, demonstrates that nausea can be a centrally driven symptom in some patients.

Various brain areas are involved in nausea and emesis without there being a single ‘emesis center’. Areas in the dorsal rostral medulla, including all the areas activated in our study have been proposed to be particularly important. The NTS plays a coordinating role and receives information from vagal afferents and the area postrema [-]. The nucleus ambiguus is involved in the respiratory related components of vomiting []. The dorsal motor nucleus of the vagus nerve causes relaxation of the lower esophageal sphincter and the gastric fundus, both of which precede emesis []. The PAG modulates the function of the nucleus ambiguus []. The PAG can also be associated with sympathetic system activation seen during nausea and emesis [,]. Cardiovascular and respiratory regulation by the PAG is mediated through ascending projections to the dorso-medial hypothalamus and descending projections to the ventral medulla []. The NTS has afferent and efferent connections with the paraventricular nucleus of the hypothalamus suggesting a role in autonomic control []. The paraventricular and dorso-medial hypothalamic nuclei form the principal central afferent input to the area postrema []. Brain areas rostral to the nucleus ambiguus are not essential for vomiting, but may initiate vomiting under certain circumstances such as to cancer chemotherapy or psychogenic vomiting []. In this regard, electrical stimulation of the preoptic and medial nuclei of the hypothalamus, the nucleus anterior ventralis of the thalamus and limbic cortical areas, such as the amygdala and hippocampus, have been shown to induce vomiting []. When we compared premonitory scans of all patients (with and without nausea) against baseline, as we have reported [], we found activations in the dorsal and lateral regions of the hypothalamus but not in anterior thalamus, hippocampus or amygdala. Therefore, considering the connections between the NTS and area postrema with the hypothalamus, the hypothalamus may play a direct or indirect role in nausea in the premonitory phase. The absence of hypothalamic activation in the nausea group could be due to low number of patients.

We cannot be certain that activation in the rostral caudal medulla itself causes nausea and vomiting or alternatively these areas are secondarily activated by other sub-cortical or cortical areas. However, the important finding is that the medullary areas are activated before the appearance of pain and hence do not represent a reaction to pain. It would therefore be reasonable to believe that nausea is centrally generated within the brain in the premonitory phase of migraine. Worsening of nausea during headache is likely to be due to the activation of functional connections between the trigeminovascular neurons and the NTS [,].

Limitations

It needs to be emphasized that studying nausea in migraine is very difficult, because patients are lying immobilized in the scanner and nausea potentially carries the risk of vomiting with aspiration. No neuroimaging study has specifically addressed nausea in migraine to date. We used data where nausea was recorded, although it was not the main outcome of the principal study. The number of patients in this pilot study was small, especially in the nausea group and group sizes are not balanced. However, each patient had three scans in baseline and between one - three scans in the premonitory phase. We have previously used a similar design using H₂¹⁵O PET with multiple scans in baseline and spontaneous migraine states and found meaningful results with five subjects []. Despite the small number in this study, the absence of activation of the NTS and surrounding areas in the no-nausea group and the presence of activation in these areas in the nausea group indicates that these areas are activated when patients experience nausea in the premonitory phase. Also, the results confirmed the a priori hypothesis that these areas would be activated. A drawback of PET studies is the low spatial resolution of the technique, which makes accurate delineation of specific nuclei difficult. Due to the inherent low spatial resolution of PET, and smoothing procedures, we cannot be certain of not missing any activation in smaller structures. Since we have not compared our findings with patients with nausea due to other reasons, we cannot be certain if the results are specific to the premonitory phase of migraine.

Conclusion

We conclude that occurrence of nausea in the premonitory phase of migraine is associated with activation of the NTS, dorsal motor nucleus of vagus, nucleus ambiguus and the PAG, in the absence of pain, and hence likely represents a primary event. This does not exclude its augmentation by trigeminal nociceptive activation as an additional pathophysiological mechanism. Future research looking into more effective anti-nausea medications for migraine should concentrate on these central sites.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

FM – study design, study conduction, data analysis, and writing of the manuscript. TS- Study design, study conduction, data analysis, and review of the manuscript. CM – study conduction. PJG - Study design, study conduction, data analysis, and final review of the manuscript. All authors read and approved the final manuscript.

Acknowledgements

We are thankful to Carole Schreck (chief PET technician); Seante Baker, BS; Janet Corroo, RN; Denise Chou MD; Henry VanBrocklin MD, and Mei Mei Church, NP. We are most grateful to all our patients for their participation in the study. Till Sprenger was supported by a grant from the Deutsche Forschungsgemeinschaft (DFG grant no. SP1215/1-1).

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