Brain-Derived Neurotrophic Factor Is Released in the Dorsal Horn by Distinctive Patterns of Afferent Fiber Stimulation

Lever, Isobel J.; Bradbury, Elizabeth J.; Cunningham, J.R.; Adelson, David; Jones, Martyn G.; McMahon, Stephen B.; Marvizón, Juan Carlos G.; Malcangio, Marzia

doi:10.1523/jneurosci.21-12-04469.2001

Cited by 272 publications

(247 citation statements)

References 63 publications

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“…It was therefore striking, when it was discovered that BDNF is normally produced by a subset of trkA positive nociceptors and that the number of trkA neurons making this factor is dramatically increased by increased NGF (Apfel et al, 1996;Michael et al, 1997). Indeed, BDNF could be shown to be released by activity in sensory neurons and its release is enhanced by elevated NGF levels that follow inflammation (Balkowiec and Katz, 2000;Lever et al, 2001). Thus, increased peripheral NGF leads to increased production and release of BDNF from the central synapses of nociceptors in the spinal cord, which may be critical for certain central sensitization events, especially those involving NMDA receptors .…”

Section: Mechanisms Of Ngf-dependent Mechanical Hyperalgesiamentioning

confidence: 99%

Nerve Growth Factor and Nociception: From Experimental Embryology to New Analgesic Therapy

Lewin

Lechner

Smith

2014

Handbook of Experimental Pharmacology

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Nerve growth factor (NGF) is central to the development and functional regulation of sensory neurons that signal the first events that lead to pain. These sensory neurons, called nociceptors, require NGF in the early embryo to survive and also for their functional maturation. The long road from the discovery of NGF and its roles during development to the realization that NGF plays a major role in the pathophysiology of inflammatory pain will be reviewed. In particular, we will discuss the various signaling events initiated by NGF that lead to long lasting thermal and mechanical hyperalgesia in animals and in man. It has been realized relatively recently that humanized, function blocking antibodies directed against NGF show remarkably analgesic potency in human clinical trials for painful conditions as varied as osteoarthritis, lower back pain and interstitial cystitis. Thus, anti-NGF medication has the potential to make a major impact on day-to-day pain treatment in the near future. It is therefore all the more important to understand the precise pathways and mechanisms that are controlled by NGF to initiate and sustain mechanical and thermal hyperalgesia. Recent work suggests that NGF-dependent regulation of the mechanosensory properties of sensory neurons that signal mechanical pain may open new mechanistic avenues to refine and exploit relevant molecular targets for novel analgesics.

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Section: Mechanisms Of Ngf-dependent Mechanical Hyperalgesiamentioning

confidence: 99%

Nerve Growth Factor and Nociception: From Experimental Embryology to New Analgesic Therapy

Lewin

Lechner

Smith

2014

Handbook of Experimental Pharmacology

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“…Moreover, Hartmann et al (2001) found that different mechanisms regulate release of BDNF-GFP in response to high-frequency presynaptic stimulation and continuous KCl depolarization, respectively. Finally, studies from this and other laboratories demonstrated that release of native BDNF from sensory neurons (Balkowiec and Katz, 2000;Lever et al, 2001) or of adenovirally overexpressed BDNF (AdVBDNF) from hippocampal neurons (Gärtner and Staiger, 2002) can be regulated by the frequency and pattern of stimulation. However, mechanisms underlying activity-dependent secretion of native BDNF from hippocampal neurons have not been defined.…”

mentioning

confidence: 90%

“…The magnitude of native BDNF release from primary sensory neurons is regulated by the frequency and pattern of stimulation (Balkowiec and Katz, 2000;Lever et al, 2001). To determine whether similar mechanisms regulate activity-dependent secretion of BDNF from hippocampal neurons, we next examined the relationship between the pattern of stimulation and the magnitude of native BDNF release in hippocampal cultures.…”

Section: Short-term Patterned Electrical Stimulation But Not Short-tmentioning

confidence: 99%

Cellular Mechanisms Regulating Activity-Dependent Release of Native Brain-Derived Neurotrophic Factor from Hippocampal Neurons

2002

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Brain-derived neurotrophic factor (BDNF) plays a critical role in activity-dependent modifications of neuronal connectivity and synaptic strength, including establishment of hippocampal long-term potentiation (LTP). To shed light on mechanisms underlying BDNF-dependent synaptic plasticity, the present study was undertaken to characterize release of native BDNF from newborn rat hippocampal neurons in response to physiologically relevant patterns of electrical field stimulation in culture, including tonic stimulation at 5 Hz, bursting stimulation at 25 and 100 Hz, and theta-burst stimulation (TBS). Release was measured using the ELISA in situ technique, developed in our laboratory to quantify secretion of native BDNF without the need to first overexpress the protein to nonphysiological levels. Each stimulation protocol resulted in a significant increase in BDNF release that was tetrodotoxin sensitive and occurred in the absence of glutamate receptor activation. However, 100 Hz tetanus and TBS, stimulus patterns that are most effective in inducing hippocampal LTP, were significantly more effective in releasing native BDNF than lower-frequency stimulation. For all stimulation protocols tested, removal of extracellular calcium, or blockade of N-type calcium channels, prevented BDNF release. Similarly, depletion of intracellular calcium stores with thapsigargin and treatment with dantrolene, an inhibitor of calcium release from caffeine-ryanodine-sensitive stores, markedly inhibited activity-dependent BDNF release. Our results indicate that BDNF release can encode temporal features of hippocampal neuronal activity. The dual requirement for calcium influx through N-type calcium channels and calcium mobilization from intracellular stores strongly implicates a role for calcium-induced calcium release in activity-dependent BDNF secretion.

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“…Calcium oscillations reduce the effective threshold for transcription factor activation and thus gene expression (27,44,52,160). For example, BDNF, a neurotrophic factor implicated in many forms of neural plasticity, exhibits pattern-sensitive, activity-dependent synthesis (166), and release (11,125), at least in some types of neurons.…”

Section: The Stimulus Paradigm Is a Key Determinant Of Plasticitymentioning

confidence: 99%

Invited Review: Neuroplasticity in respiratory motor control

Mitchell

Johnson

2003

Journal of Applied Physiology

354

313

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Although recent evidence demonstrates considerable neuroplasticity in the respiratory control system, a comprehensive conceptual framework is lacking. Our goals in this review are to define plasticity (and related neural properties) as it pertains to respiratory control and to discuss potential sites, mechanisms, and known categories of respiratory plasticity. Respiratory plasticity is defined as a persistent change in the neural control system based on prior experience. Plasticity may involve structural and/or functional alterations (most commonly both) and can arise from multiple cellular/synaptic mechanisms at different sites in the respiratory control system. Respiratory neuroplasticity is critically dependent on the establishment of necessary preconditions, the stimulus paradigm, the balance between opposing modulatory systems, age, gender, and genetics. Respiratory plasticity can be induced by hypoxia, hypercapnia, exercise, injury, stress, and pharmacological interventions or conditioning and occurs during development as well as in adults. Developmental plasticity is induced by experiences (e.g., altered respiratory gases) during sensitive developmental periods, thereby altering mature respiratory control. The same experience later in life has little or no effect. In adults, neuromodulation plays a prominent role in several forms of respiratory plasticity. For example, serotonergic modulation is thought to initiate and/or maintain respiratory plasticity following intermittent hypoxia, repeated hypercapnic exercise, spinal sensory denervation, spinal cord injury, and at least some conditioned reflexes. Considerable work is necessary before we fully appreciate the biological significance of respiratory plasticity, its underlying cellular/molecular and network mechanisms, and the potential to harness respiratory plasticity as a therapeutic tool.

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Brain-Derived Neurotrophic Factor Is Released in the Dorsal Horn by Distinctive Patterns of Afferent Fiber Stimulation

Cited by 272 publications

References 63 publications

Nerve Growth Factor and Nociception: From Experimental Embryology to New Analgesic Therapy

Nerve Growth Factor and Nociception: From Experimental Embryology to New Analgesic Therapy

Cellular Mechanisms Regulating Activity-Dependent Release of Native Brain-Derived Neurotrophic Factor from Hippocampal Neurons

Invited Review: Neuroplasticity in respiratory motor control

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