Increased Levels of Neurotrophins Are Not Specific for Chronic Migraine: Evidence From Primary Fibromyalgia Syndrome

Sarchielli, Paola; Mancini, Maria Luisa; Floridi, Ardesio; Coppola, Francesca; Rossi, Cristiana; Nardi, Katiuscia; Acciarresi, Monica; Pini, Luigi Alberto; Calabresi, Paolo

doi:10.1016/j.jpain.2007.05.002

Cited by 137 publications

(117 citation statements)

References 69 publications

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“…In adults, neurotrophic factors such as nerve growth factor (NGF) regulate gene expression after nerve injury or prolonged inflammation, which can lead to the development of persistent pain (Zhu and Oxford, 2011). Endogenous NGF levels are elevated in certain chronic pain conditions (Aloe et al, 1992;Iannone et al, 2002;Sarchielli et al, 2007) and a single administration of NGF is sufficient to trigger transition to a persistent pain state in humans that lasts for weeks (Petty et al, 1994;Dyck et al, 1997;Svensson et al, 2003;Rukwied et al, 2010). NGF is also synthesized and released upon single or repeated tissue injury/inflammation (Paterson et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Persistent Nociception Triggered by Nerve Growth Factor (NGF) Is Mediated by TRPV1 and Oxidative Mechanisms

et al. 2015

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Nerve growth factor (NGF) is elevated in certain chronic pain conditions and is a sufficient stimulus to cause lasting pain in humans, but the actual mechanisms underlying the persistent effects of NGF remain incompletely understood. We developed a rat model of NGFinduced persistent thermal hyperalgesia and mechanical allodynia to determine the role of transient receptor potential vanilloid 1 (TRPV1) and oxidative mechanisms in the persistent effects of NGF. Persistent thermal hypersensitivity and mechanical allodynia require de novo protein translation and are mediated by TRPV1 and oxidative mechanisms. By comparing effects after systemic (subcutaneous), spinal (intrathecal) or hindpaw (intraplantar) injections of test compounds, we determined that TRPV1 and oxidation mediate persistent thermal hypersensitivity via peripheral and spinal sites of action and mechanical allodynia via only a spinal site of action. Therefore, NGF-evoked thermal and mechanical allodynia are mediated by spatially distinct mechanisms. NGF treatment evoked sustained increases in peripheral and central TRPV1 activity, as demonstrated by increased capsaicin-evoked nocifensive responses, increased calcitonin gene-related peptide release from hindpaw skin biopsies, and increased capsaicin-evoked inward current and membrane expression of TRPV1 protein in dorsal root ganglia neurons. Finally, we showed that NGF treatment increased concentrations of linoleic and arachidonic-acid-derived oxidized TRPV1 agonists in spinal cord and skin biopsies. Furthermore, increases in oxidized TRPV1-active lipids were reduced by peripheral and spinal injections of compounds that completely blocked persistent nociception. Collectively, these data indicate that NGF evokes a persistent nociceptive state mediated by increased TRPV1 activity and oxidative mechanisms, including increased production of oxidized lipid TRPV1 agonists.

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Section: Introductionmentioning

confidence: 99%

Persistent Nociception Triggered by Nerve Growth Factor (NGF) Is Mediated by TRPV1 and Oxidative Mechanisms

et al. 2015

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“…Some studies have proposed that pro-and anti-inflammatory molecules may play a role in the pathophysiology of migraine 8,9,10 and TTH 11,12,13 . The association between neurotrophic factors and migraine 14,15,16 , and neurotrophic factors and TTH 17,18 has also been investigated. As different pathophysiological mechanisms have been proposed for migraine and TTH, it is possible that the profile of these molecules may be distinct in these two disorders.…”

mentioning

confidence: 99%

Serum levels of adiponectin, CCL3/MIP-1α, and CCL5/RANTES discriminate migraine from tension-type headache patients

Domingues

Duarte

Senne

et al. 2016

Arq. Neuro-Psiquiatr.

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Migraine and tension-type headache (TTH) are the most frequent primary headaches and their differentiation is based on strict clinical diagnostic criteria 1 . Though different theories have been formulated to explain these disorders, their physiopathology remains largely unknown.Migraine is considered a neurovascular disorder with complex genetic background. Trigeminovascular system activation with subsequent release of vasoactive neuropeptides has been proposed to explain migraine attacks 2 , while central sensitization possibly plays a role in migraine chronification 3 . Conversely, TTH pathophysiology has been thought to be associated with both peripheral (increased myofascial pain sensitivity and peripheral sensitization of myofascial nociceptors) and central ABSTRACTObjectives: Inflammatory molecules and neurotrophic factors are implicated in pain modulation; however, their role in primary headaches is not yet clear. The aim of this study was to compare the levels of serum biomarkers in migraine and tension-type headache. Methods: This was a cross-sectional study. We measured serum levels of adiponectin, chemokines, and neurotrophic factors in patients with migraine and tension-type headache. Depression and anxiety symptoms, headache impact and frequency, and allodynia were recorded. Results: We included sixty-eight patients with migraine and forty-eight with tension-type headache. Cutaneous allodynia (p = 0.035), CCL3/MIP-1α (p = 0.041), CCL5/RANTES (p = 0.013), and ADP (p = 0.017) were significantly higher in migraine than in tension-type headache. The differences occurred independently of anxiety and depressive symptoms, frequency and impact of headache, and the presence of pain. Conclusions: This study showed higher CCL3/MIP-1α, CCL5/RANTES, and ADP levels in migraine in comparison with tension-type headache. Our findings suggest distinctive roles of these molecules in the pathophysiology of these primary headaches.Keywords: migraine disorders; tension-type headache; adiponectin; chemokines; neurotrophic factors. RESUMO Objetivos:Moléculas inflamatórias e fatores neurotróficos estão implicados na modulação dolorosa, contudo, seu papel nas cefaleias primárias não é claro. O objetivo do presente estudo foi comparar níveis de biomarcadores séricos na migrânea e cefaleia do tipo tensional. Métodos: Este foi um estudo transversal, no qual foram avaliados níveis de adiponectina, quimiocinas e fatores neurotróficos em pacientes com migrânea e cefaleia do tipo tensional. Sintomas depressivos e ansiosos, o impacto e a frequência da cefaleia e alodínea foram registrados. Resultados: Foram incluídos 68 pacientes com migrânea e 48 pacientes com cefaleia do tipo tensional. A alodínia cutânea (p = 0.035), CCL3/MIP-1α (p = 0.041), CCL5/RANTES (p = 0.013), e adiponectina (p = 0.017) foram maiores na migrânea, independentemente de sintomas depressivos e ansiosos, frequência e impacto da cefaleia. Conclusões: Níveis de CCL3/MIP-1α, CCL5/RANTES e adiponectina foram maiores na migrânea do que na cefaleia do tipo tensional...

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“…The binding of Glu to ionotropic receptors increases the sodium permeability of neuronal membranes and results in cell activation (i.e., membrane depolarization). Since elevated Glu levels have been reported in the cerebrospinal fluid of patients with FM (9), it is reasonable to suspect that this molecule may be responsible for the augmented pain transmission observed in FM (2,3).…”

mentioning

confidence: 99%

Dynamic levels of glutamate within the insula are associated with improvements in multiple pain domains in fibromyalgia

Harris¹,

Sundgren²,

Pang³

et al. 2008

Arthritis & Rheumatism

185

161

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Objective. Fibromyalgia (FM) is a chronic widespread pain condition that is thought to arise from augmentation of central neural activity. Glutamate (Glu) is an excitatory neurotransmitter that functions in pain-processing pathways. This study was carried out to investigate the relationship between changing levels of Glu within the insula and changes in multiple pain domains in patients with FM.Methods. Ten patients with FM underwent 2 sessions of proton magnetic resonance spectroscopy (H-MRS) and 2 sessions of functional magnetic resonance imaging (FMRI), each conducted before and after a nonpharmacologic intervention to reduce pain. During H-MRS, the anterior and posterior insular regions were examined separately using single-voxel spectroscopy. The levels of Glu and other metabolites were estimated relative to levels of creatine (Cr) (e.g., the Glu/Cr ratio). During FMRI, painful pressures were applied to the thumbnail to elicit neuronal activation. Fibromyalgia (FM) is a chronic widespread pain disorder that affects ϳ2-4% of individuals in industrialized countries (1). Although the underlying etiology of this condition is unknown, dysfunction within the central nervous system has been implicated. Results from functional magnetic resonance imaging (FMRI) (2,3), singlephoton emission tomography (4), and positron emission tomography (5) support this hypothesis.One structure that is consistently found to be associated with augmented evoked pain activity in FM is the insula (2,3). In addition to its function in speech, taste, and auditory systems, the insula is also intimately involved in somatosensory and visceral pain processing (6). It is strategically located in a bidirectional pathway between the secondary somatosensory cortex and the amygdala (6). This anatomic position may give the insula ClinicalTrials.gov identifier: NCT00142597.

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Increased Levels of Neurotrophins Are Not Specific for Chronic Migraine: Evidence From Primary Fibromyalgia Syndrome

Cited by 137 publications

References 69 publications

Persistent Nociception Triggered by Nerve Growth Factor (NGF) Is Mediated by TRPV1 and Oxidative Mechanisms

Persistent Nociception Triggered by Nerve Growth Factor (NGF) Is Mediated by TRPV1 and Oxidative Mechanisms

Serum levels of adiponectin, CCL3/MIP-1α, and CCL5/RANTES discriminate migraine from tension-type headache patients

Dynamic levels of glutamate within the insula are associated with improvements in multiple pain domains in fibromyalgia

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