Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although migraine is inextricably bound up with 5-hydroxytryptamine and its many receptors, its precise mechanisms continue to elude us and there is still no clear evidence supporting either a vascular or neurogenic hypothesis unequivocally. What appears to distinguish migraine sufferers from normal subjects may be a greater gentic sensitivity to a wide variety of triggering agents--even including nitric oxide and the migraine aura, as well as those more usually recognized. Attention is drawn to a possible role for neurotrophins, such as the hyperalgesia-provoking nerve growth factor (NGF) in particular, as well as basic fibroblast growth factor (bFGF) and brain-derived neurotrophic factor (BDNF).
Cephalalgia 1995
PMID:Migraine to the year 2000. 758 20

Intrathecal (i.t.) drug application is accepted as a highly effective treatment option for various neurological conditions. Technical risks and potentially dangerous complications require appreciation. We present the case of a patient treated with i.t. recombinant, human brain-derived neurotrophic factor (rhBDNF) as an experimental therapy for amyotrophic lateral sclerosis (ALS). Five days after starting the i.t. drug infusion, she complained of severe headache and nausea. Radiological studies suggested the catheter was located within the epi-arachnoidal space. A deposit of more than 10 ml secluded from the subarachnoidal space was found within this space. I.t. contained a high concentration of the applied drug. Revision of the catheter resulted in complete recovery from symptoms and i.t. infusion could be continued. The epi-arachnoidal positioning of a spinal catheter is a potential cause for treatment failure. If the membrane around the fluid deposit ruptures, the drug could be released into the subarachnoidal space, with the consequence of a potentially life-threatening complication.
 ...
PMID:Epi-arachnoidal drug deposit: a rare complication of intrathecal drug therapy. 1051 46

The pivotal role of nerve growth factor in inducing hyperalgesia and central sensitization has been emphasized in experimental pain models. Higher nerve growth factor levels have recently been found in the cerebrospinal fluid of patients with chronic daily headache. These levels were significantly correlated with the cerebrospinal fluid levels of substance P and calcitonin gene-related peptide, supporting the involvement of this neurotrophin in enhancing the production of the two sensory neuropeptides of the trigemino-vascular system in chronic daily headache. This may, in part, account for the long-lasting sensitization and activation of this system, which could contribute to headache chronicity. More recent research has shown a significant correlation between the higher cerebrospinal fluid levels of nerve growth factor and those of another neurotrophin, the brain-derived neurotrophic factor, as well as glutamate in chronic daily headache patients. These findings suggest the potential involvement of nerve growth factor-mediated upregulation of brain-derived neurotrophic factor in persistent head pain. Therefore, nerve growth factor appears to indirectly exert its effect through enhancing glutamatergic transmission involved in the processing of head pain via brain-derived neurotrophic factor. Based on these data, a potential application can be hypothesized for novel strategies targeting neurotrophins (nerve growth factor and brain-derived neurotrophic factor) and their receptors to chronic daily headache. To date, the majority of the molecules discovered in this regard have been scarcely or never proved in animal pain models and are far from clinical use in chronic pain, including chronic daily headache. If this approach is to be developed in the near future, research should be focused on identifying strategies with few central side effects and specific selective action on central sites involved in chronic head pain and more generally in chronic pain conditions. This will represent a very difficult challenge, taking into account the pleiotropic effect of nerve growth factor and the wide range of intracellular signalling pathways activated by this neurotrophin which are not limited to the nociceptive system.
 ...
PMID:Nerve growth factor and chronic daily headache: a potential implication for therapy. 1585 22

Neurotrophins, such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), have been implicated in the generation and modulation of pain. To investigate whether alterations in neurotrophin levels can be detected in subjects suffering from nociceptive disorders, such as primary headaches, we determined the peripheral (platelet and plasma) levels of BDNF and NGF in patients suffering from migraine, with or without aura, or cluster headache (CH), in the interictal phase, and in healthy volunteers. All primary headaches patients studied showed significantly decreased platelet levels of BDNF (migraine vs. controls P<0.001; CH vs. controls P<0.01), while a selective reduction of platelet NGF was observed in migraine sufferers and not in CH patients compared with control subjects (migraine vs. controls P<0.001). These changes were not accompanied by significant modifications of neurotrophin plasma levels. Our findings show for the first time that changes in peripheral levels of neurotrophines (BDNF and NGF) occur in patients suffering from different types of primary headaches, suggesting a potential involvement of BDNF and NGF in the pathophysiology of these disorders, and raising the possibility that differences in peripheral neurotrophins may help to distinguish migraine biologically from CH.
Cephalalgia 2006 Feb
PMID:Peripheral levels of BDNF and NGF in primary headaches. 1642 67

Estrogen has diverse and powerful effects in the brain, including actions on neurons, glia, and the vasculature. It is not surprising, therefore, that there are many changes in the female brain as serum estradiol levels rise and fall during the normal ovarian cycle. At times of life when estradiol levels change dramatically, such as puberty, postpartum, or menopause, there also are dramatic changes in the central nervous system. Changes that occur because of fluctuations in serum estrogen levels are potentially relevant to neurological disorders because symptoms often vary with the time of the ovarian cycle. Moreover, neurological disorders (eg, seizures and migraine) often increase in frequency in women when estradiol levels change. In this review, the contribution of 2 growth factors targeted by estrogen, the neurotrophin brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF), will be discussed. Estrogen-sensitive response elements are present on the genes for both BDNF and VEGF, and they are potent modulators of neuronal, glial, and vascular function, making them logical candidates to mediate the multitude of effects of estrogen. In addition, BDNF induces neuropeptide Y, which has diverse actions that are relevant to estrogen action and to the same neurological disorders.
Headache 2008 Jul
PMID:Estrogen-growth factor interactions and their contributions to neurological disorders. 1870 Sep 46

Medication overuse headache (MOH) can be considered a clinical condition at the boundaries between drug addiction and chronic pain disorder. The common 196G > A single-nucleotide polymorphism of BDNF gene, resulting in a valine 66 to methionine (Val66Met), is related with behaviour disorders and substance abuse. With the aim of identifying a worsening factor in MOH, rather than the detection of a specific risk factor for the development of the disease, we investigated whether the presence of a functional BDNF polymorphism might determine clinical differences within a group of 90 MOH patients, particularly in monthly drug consumption, that is the hallmark of disease. Directly comparing MOH patients homozygous for G allele (G/G) with carriers of A allele (non-G/G), we have observed 47 G/G genotypes and 60 non-G/G genotypes. Non-G/G had a higher consumption of monthly drug number (Cohen's d = 0.76) than G/G patients. At multiple regression analysis, the Val66Met BDNF polymorphism emerged as a significant independent predictor of analgesic drug consumption (Beta = 0.33, Cohen's f(2) = 0.134). These findings showed an influence of examined BDNF polymorphism in the MOH clinical features, supporting the idea that MOH is a substance abuse disorder.
J Headache Pain 2009 Oct
PMID:Drug consumption in medication overuse headache is influenced by brain-derived neurotrophic factor Val66Met polymorphism. 1951 61

Fibromyalgia syndrome (FMS) is a common chronic pain condition characterized by chronic widespread pain and decreased pain threshold, with hyperalgesia and allodynia. Associated signs include fatigue, morning stiffness, non-restorative sleep, mood disturbance, depression, irritable bowel syndrome, and headache. In addition to the administration of drugs, psychological therapies treatment of FMS mainly consists of physical therapies. Although the precise pathogenesis of FMS remains elucidated, modern understanding conceptualizes FMS as central sensitization as a consequence of altered endogenous pain- and stress-response system and continuous nociceptive input. Altered brain-derived neurotrophic factor (BDNF) levels in FMS suggest that BDNF--well known for its effects on neuronal plasticity--is involved in this sensitization process. Exercise leads to changes in serum BDNF levels, too. This association highlights the importance of exercise in FMS and other chronic pain conditions.
 ...
PMID:Brain-derived neurotrophic factor and exercise in fibromyalgia syndrome patients: a mini review. 2221 Feb 72

Many non-pharmacological treatments have been implicated in the treatment of primary headache, with exercise being a common recommendation. In this review we first provide an overview of the relationship between exercise and primary headaches. We then review the physiology of pain modulation, with focus on the endogenous opioids, endocannabinoids, and neuropeptides calcitonin gene-related peptide (CGRP) and brain-derived neurotrophic factor (BDNF), and their associations with primary headache and exercise. Finally, we summarize current literature evaluating effects of exercise on primary headache in an effort to understand the benefits and disadvantages of exercise in primary headaches.
Curr Pain Headache Rep 2013 Dec
PMID:Does exercise make migraines worse and tension type headaches better? 2423 18

It is well established that the majority of headache and other trigeminal nerve-associated disorders have higher prevalence in females than in males. However, the pathogenesis of many chronic trigeminal pain conditions, such as trigeminal neuralgia, migraine and temporo-mandibular disorders, is still not known. One of the proposed mechanisms involve calcitonin gene-related peptide (CGRP), which is considered the most important neuropeptide in the trigeminal system. In various animal models of trigeminal nerve-associated disorders concentration of CGRP has been shown to be increased in trigeminal ganglia (TG). Moreover, intraganglionic release of CGRP has been shown to modulate neuronal transmission of pain signals. In most of these models, pathological changes in the trigeminal system are accompanied by inflammation within peripheral endings of TG neurons. The aim of the present study was to investigate the relation between gender and neurochemical changes in trigeminal ganglia evoked by peripheral inflammation, induced by Complete Freund Adjuvant (CFA) administration. Our studies show significant increase in CGRP expression in female mice, comparing to male mice. Furthermore, we demonstrate, that activation of trigeminal nociceptors by peripheral inflammation causes significant increase in expression of IL-1B, IL-6, TNF and BDNF in male mice, comparing to female mice. This phenomenon may be involved in clinically observed gender-dependent differences in the frequency of both migraine and other trigeminal nerve-related facial pain disorders.
...
PMID:Gender differences in the neurochemical response of trigeminal ganglion neurons to peripheral inflammation in mice. 2499 32

Migraine is one of the most common and most disabling disorders. Between attacks, migraine patients are otherwise normal but are sensitized to nonnoxious events known as triggers. The purpose of these studies was to investigate whether a headache-like event causes sensitization, or priming, to subsequent subthreshold events. Interleukin-6 (IL-6) was applied to the rat cranial dura mater which produced cutaneous facial and hind paw allodynia that lasted 24 hours. At 72 hours, IL-6-treated rats developed allodynia in response to dural stimulation with either a pH 6.8 or pH 7.0 solution and to a systemic nitric oxide (NO) donor, a well-known migraine trigger. Vehicle-treated rats did not respond to either pH stimulus or to the NO donor, demonstrating that IL-6 exposure primes rats to subthreshold stimuli. Inhibitors of brain-derived neurotrophic factor (BDNF) signaling given either systemically or intracisternally 24 hours after IL-6 eliminated responses to dural pH stimulation at 72 hours. Additionally, intracisternal administration of BDNF without previous dural stimulation produced allodynia and once resolved, animals were primed to dural pH 6.8/pH 7.0 and a systemic NO donor. Finally, hind paw IL-6 produced paw allodynia but not priming to paw injection of pH 7.0 at 72 hours demonstrating differences in priming depending on location. These data indicate that afferent input from the meninges produces BDNF-dependent priming of the dural nociceptive system. This primed state mimics the interictal period of migraine where attacks can be triggered by normally nonnoxious events and suggests that BDNF-dependent plasticity may contribute to migraine.
 ...
PMID:Dural stimulation in rats causes brain-derived neurotrophic factor-dependent priming to subthreshold stimuli including a migraine trigger. 2784 39


1 2 Next >>