Nociceptor-derived brain-derived neurotrophic factor regulates acute and inflammatory but not neuropathic pain. 2006

Jing Zhao, and Anjan Seereeram, and Mohammed A Nassar, and Alessandra Levato, and Sophie Pezet, and Gareth Hathaway, and Cruz Morenilla-Palao, and Caroline Stirling, and Maria Fitzgerald, and Stephen B McMahon, and Maribel Rios, and John N Wood, and
Molecular Nociception Group, Department of Biology, University College London, London WC1E 6BT, UK.

Conditional mouse knock-outs provide an informative approach to drug target validation where no pharmacological blockers exist or global knock-outs are lethal. Here, we used the Cre-loxP system to delete BDNF in most nociceptive sensory neurons. Conditional null animals were healthy with no sensory neuron loss. However, pain-related behavior was substantially altered. Baseline thermal thresholds were reduced. Carrageenan-induced thermal hyperalgesia was inhibited. Formalin-induced pain behavior was attenuated in the second phase, and this correlated with abolition of NMDA receptor NR1 Ser896/897 phosphorylation and ERK1 and ERK2 activation in the dorsal horn; AMPA receptor phosphorylation (GluR1/Ser831) was unaffected. NGF-induced thermal hyperalgesia was halved, and mechanical secondary hyperalgesia caused by intramuscular NGF was abolished. By contrast, neuropathic pain behavior developed normally. Nociceptor-derived BDNF thus plays an important role in regulating inflammatory pain thresholds and secondary hyperalgesia, but BDNF released only from nociceptors plays no role in the development of neuropathic pain.

UI MeSH Term Description Entries
D007249 Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D009437 Neuralgia Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. Nerve Pain,Neurodynia,Paroxysmal Nerve Pain,Neuralgia, Atypical,Neuralgia, Iliohypogastric Nerve,Neuralgia, Ilioinguinal,Neuralgia, Perineal,Neuralgia, Stump,Neuralgia, Supraorbital,Neuralgia, Vidian,Neuropathic Pain,Atypical Neuralgia,Atypical Neuralgias,Iliohypogastric Nerve Neuralgia,Iliohypogastric Nerve Neuralgias,Ilioinguinal Neuralgia,Ilioinguinal Neuralgias,Nerve Neuralgia, Iliohypogastric,Nerve Neuralgias, Iliohypogastric,Nerve Pain, Paroxysmal,Nerve Pains,Nerve Pains, Paroxysmal,Neuralgias,Neuralgias, Atypical,Neuralgias, Iliohypogastric Nerve,Neuralgias, Ilioinguinal,Neuralgias, Perineal,Neuralgias, Stump,Neuralgias, Supraorbital,Neuralgias, Vidian,Neurodynias,Neuropathic Pains,Pain, Nerve,Pain, Neuropathic,Pain, Paroxysmal Nerve,Pains, Nerve,Pains, Neuropathic,Pains, Paroxysmal Nerve,Paroxysmal Nerve Pains,Perineal Neuralgia,Perineal Neuralgias,Stump Neuralgia,Stump Neuralgias,Supraorbital Neuralgia,Supraorbital Neuralgias,Vidian Neuralgia,Vidian Neuralgias
D009475 Neurons, Afferent Neurons which conduct NERVE IMPULSES to the CENTRAL NERVOUS SYSTEM. Afferent Neurons,Afferent Neuron,Neuron, Afferent
D009619 Nociceptors Peripheral AFFERENT NEURONS which are sensitive to injuries or pain, usually caused by extreme thermal exposures, mechanical forces, or other noxious stimuli. Their cell bodies reside in the DORSAL ROOT GANGLIA. Their peripheral terminals (NERVE ENDINGS) innervate target tissues and transduce noxious stimuli via axons to the CENTRAL NERVOUS SYSTEM. Pain Receptors,Receptors, Pain,Nociceptive Neurons,Neuron, Nociceptive,Neurons, Nociceptive,Nociceptive Neuron,Nociceptor,Pain Receptor
D010147 Pain Measurement Scales, questionnaires, tests, and other methods used to assess pain severity and duration in patients or experimental animals to aid in diagnosis, therapy, and physiological studies. Analgesia Tests,Analogue Pain Scale,Formalin Test,McGill Pain Questionnaire,Nociception Tests,Pain Assessment,Pain Intensity,Pain Severity,Tourniquet Pain Test,Visual Analogue Pain Scale,Analog Pain Scale,Assessment, Pain,McGill Pain Scale,Visual Analog Pain Scale,Analgesia Test,Analog Pain Scales,Analogue Pain Scales,Formalin Tests,Intensity, Pain,Measurement, Pain,Nociception Test,Pain Assessments,Pain Intensities,Pain Measurements,Pain Questionnaire, McGill,Pain Scale, Analog,Pain Scale, Analogue,Pain Scale, McGill,Pain Severities,Pain Test, Tourniquet,Questionnaire, McGill Pain,Scale, Analog Pain,Scale, Analogue Pain,Scale, McGill Pain,Severity, Pain,Test, Analgesia,Test, Formalin,Test, Nociception,Test, Tourniquet Pain,Tests, Nociception,Tourniquet Pain Tests
D010523 Peripheral Nervous System Diseases Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves. Peripheral Nerve Diseases,Peripheral Neuropathies,PNS (Peripheral Nervous System) Diseases,PNS Diseases,Peripheral Nervous System Disease,Peripheral Nervous System Disorders,Nerve Disease, Peripheral,Nerve Diseases, Peripheral,Neuropathy, Peripheral,PNS Disease,Peripheral Nerve Disease,Peripheral Neuropathy
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D005260 Female Females

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