Jennifer Brawn

Concurrent functional and structural cortical alterations in migraine.

Aim: Various animal and human studies have contributed to the idea of cortical structural–functional alterations in migraine. Defining concurrent cortical alterations may provide specific insights into the unfolding adaptive or maladaptive changes taking place in cortex in migraine. Methods: From a group of 60 episodic migraineurs, 20 were recruited to the study. Using high-resolution magnetic resonance imaging, structural and functional cortical measures were compared in migraineurs who experienced increased frequency of attacks (HF; 8–14 days/month; n = 10), to those who experienced less frequent migraine attacks (LF; < 2 days/month; n = 10), and to healthy controls (HC; n = 20). Results: Parallel structural and functional differences were found as follows: (i) HF patients showed higher thickness in the area representing the face in the post-central gyrus, which correlated with the observed stronger functional activation, suggesting adaptation to repeated sensory drive; (ii) smaller cortical volume was observed in the cingulate cortex that correlated with lower activation in the HF group; and (iii) similarly significant structural and functional differences (HF > LF) were observed in the insula that may reflect potential alteration in affective processing. Conclusion: These results suggest differential response patterns in the sensory vs. affective processing regions in the brain that may be an adaptive response to repeated migraine attacks.

Migraine attacks the Basal Ganglia

BackgroundWith time, episodes of migraine headache afflict patients with increased frequency, longer duration and more intense pain. While episodic migraine may be defined as 1-14 attacks per month, there are no clear-cut phases defined, and those patients with low frequency may progress to high frequency episodic migraine and the latter may progress into chronic daily headache (> 15 attacks per month). The pathophysiology of this progression is completely unknown. Attempting to unravel this phenomenon, we used high field (human) brain imaging to compare functional responses, functional connectivity and brain morphology in patients whose migraine episodes did not progress (LF) to a matched (gender, age, age of onset and type of medication) group of patients whose migraine episodes progressed (HF).ResultsIn comparison to LF patients, responses to pain in HF patients were significantly lower in the caudate, putamen and pallidum. Paradoxically, associated with these lower responses in HF patients, gray matter volume of the right and left caudate nuclei were significantly larger than in the LF patients. Functional connectivity analysis revealed additional differences between the two groups in regard to response to pain.ConclusionsSupported by current understanding of basal ganglia role in pain processing, the findings suggest a significant role of the basal ganglia in the pathophysiology of the episodic migraine.

Central changes associated with chronic pelvic pain and endometriosis

BACKGROUND Chronic pelvic pain (CPP) is a significant public health problem with 1 million affected women in the UK. Although many pathologies are associated with CPP, the pain experienced is often disproportionate to the extent of disease identified and frequently no pathology is found (chronic pelvic pain syndrome). The central nervous system (CNS) is central to the experience of pain and chronic pain conditions in general are associated with alterations in both the structure and function of the CNS. This review describes the available evidence for central changes in association with conditions presenting with CPP. METHODS A detailed literature search was performed to identify relevant papers, however, this is not a systematic review. RESULTS CPP is associated with central changes similar to those identified in other pain conditions. Specifically these include, alterations in the behavioural and central response to noxious stimulation, changes in brain structure (both increases and decreases in the volume of specific brain regions), altered activity of both the hypothalamic-pituitary-adrenal axis and the autonomic nervous system (ANS) and psychological distress. CONCLUSIONS The evidence reviewed in this paper demonstrates that CPP is associated with significant central changes when compared with healthy pain-free women. Moreover, the presence of these changes has the potential to both exacerbate symptoms and to predispose these women to the development of additional chronic conditions. These findings support the use of adjunctive medication targeting the CNS in these women.

Peripheral changes in endometriosis-associated pain

BACKGROUND Pain remains the cardinal symptom of endometriosis. However, to date, the underlying mechanisms are still only poorly understood. Increasing evidence points towards a close interaction between peripheral nerves, the peritoneal environment and the central nervous system in pain generation and processing. Recently, studies demonstrating nerve fibres and neurotrophic and angiogenic factors in endometriotic lesions and their vicinity have led to increased interest in peripheral changes in endometriosis-associated pain. This review focuses on the origin and function of these nerves and factors as well as possible peripheral mechanisms that may contribute to the generation and modulation of pain in women with endometriosis. METHODS We conducted a systematic search using several databases (PubMed, MEDLINE, EMBASE and CINAHL) of publications from January 1977 to October 2013 to evaluate the possible roles of the peripheral nervous system in endometriosis pathophysiology and how it can contribute to endometriosis-associated pain. RESULTS Endometriotic lesions and peritoneal fluid from women with endometriosis had pronounced neuroangiogenic properties with increased expression of new nerve fibres, a shift in the distribution of sensory and autonomic fibres in some locations, and up-regulation of several neurotrophins. In women suffering from deep infiltrating endometriosis and bowel endometriosis, in which the anatomical distribution of lesions is generally more closely related to pelvic pain symptoms, endometriotic lesions and surrounding tissues present higher nerve fibre densities compared with peritoneal lesions and endometriomas. More data are needed to fully confirm a direct correlation between fibre density in these locations and the amount of perceived pain. A better correlation between the presence of nerve fibres and pain symptoms seems to exist for eutopic endometrium. However, this appears not to be exclusive to endometriosis. No correlation between elevated neurotrophin levels and pain severity appears to exist, suggesting the involvement of other mediators in the modulation of pain. CONCLUSIONS The increased expression of neurotrophic factors and nerve fibres in endometriotic lesions, eutopic endometrium and the peritoneum imply a role of such peripheral changes in the pathogenesis of endometriosis-associated pain. However, a clear link between these findings and pain in patients with endometriosis has so far not been demonstrated.

Pain response measured with arterial spin labeling.

The majority of functional MRI studies of pain processing in the brain use the blood oxygenation level‐dependent (BOLD) imaging approach. However, the BOLD signal is complex as it depends on simultaneous changes in blood flow, vascular volume and oxygen metabolism. Arterial spin labeling (ASL) perfusion imaging is another imaging approach in which the magnetically labeled arterial water is used as an endogenous tracer that allows for direct measurement of cerebral blood flow. In this study, we assessed the pain response in the brain using a pulsed‐continuous arterial spin labeling (pCASL) approach and a thermal stimulation paradigm. Using pCASL, response to noxious stimulation was detected in somatosensory cortex, anterior cingulate cortex, anterior insula, hippocampus, amygdala, thalamus and precuneus, consistent with the pain response activation patterns detected using the BOLD imaging approach. We suggest that pCASL is a reliable alternative for functional MRI pain studies in conditions in which blood flow, volume or oxygen extraction are altered or compromised. Copyright

A new electronic diary tool for mapping and tracking spatial and temporal head pain patterns in migraine.

Aim We present an electronic tool for collecting data on the patterns of migraine headache onset and progression. Methods A digitized map consisting of 44 color-coded segments was defined based on previous reports of migraine pain and the distribution of nerves in the face, head and neck. The map was overlaid on a schematic map of the face, head and neck nerves. Thirty-six patients (N = 36, 28 female/eight male), who met ICDH-II criteria for episodic migraine and had headaches for at least three years, identified all regions where pain typically started and how pain spread and subsequently progressed. Results Consistent with previous findings, throbbing was the most prevalent quality of migraine pain, always present in 70% of patients surveyed. For the 70% of the patients with throbbing pain, the temple was the onset site of throbbing pain, with no significant difference in the laterality of onset site (58.3% on the right vs. 55.6% on the left hemisphere). The tool was able to capture patterns of pain distribution for throbbing and pressure headache pain and also may be used to assess the change in the pattern of the pain distribution as the disease progresses. Discussion The pain map survey may be a useful tool for recording and tracking the temporal pattern of migraine onset both for clinical and research purposes. The tool could be used to create maps of pain locations on a large population scale and thus will be a very useful tool in correlating the temporal nature of headache symptoms with potential mechanisms of disease evolution.

Hormonal Influences on Magnetic Resonance Spectroscopy Measures

Hormones have long been known to have important physiological influences on the body. However, an increasing body of literature now also documents their effects on the brain (McEwen, 2012). Moreover, it is not just the hormones themselves that influence neurobiology; both their precursors and derivatives also play an important role. This chapter highlights the possible confounds that may be introduced if they are not considered in all experimental designs. We will begin by giving a brief overview of the synthesis and functions of the hormones of interest and will then review the research to date demonstrating an influence on MRS measures. While many excellent studies exist examining the role of hormones on brain neurochemistry, they do not provide enough information to paint the full biological picture. The current body of research varies in region of interest, neurochemicals studied, and hormones measured. It is clear that more studies are needed to corroborate previous findings as well as clarify current contradictions. Moving forward, researchers should try to better define how hormones differentially affect brain regions since fluctuations in neurotransmitters, such as GABA, have been found to vary.