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Peripheral brain derived neurotrophic factor (proBDNF) for regulating pain as inflammatory medium

A neurotrophic factor, brain-derived technology, applied in medicines, peripheral brain-derived neurotrophic factor precursors as inflammatory mediators in the field of pain regulation, can solve problems such as poorly understood biological roles

Inactive Publication Date: 2017-10-31
周意
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the role of proBDNF in the central nervous system has been extensively studied, the biological role of proBDNF in peripheral tissues remains poorly understood

Method used

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  • Peripheral brain derived neurotrophic factor (proBDNF) for regulating pain as inflammatory medium
  • Peripheral brain derived neurotrophic factor (proBDNF) for regulating pain as inflammatory medium
  • Peripheral brain derived neurotrophic factor (proBDNF) for regulating pain as inflammatory medium

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0078] Upregulation of proBDNF expression

[0079] 1. Immunofluorescence double labeling: mice were perfused with 4% paraformaldehyde under chloral hydrate anesthesia, then fixed in 10% formalin, dehydrated, embedded in paraffin, and sectioned. After the paraffin sections were heated for antigen retrieval and BSD blocking, mouse anti-human proBDNF monoclonal antibody (Abcam Company, 1:1000) and anti-IL-1β polyclonal antibody (Cell Signaling Company, 1:1000) or IL-6 Polyclonal antibody (Cell Signaling, 1:1000) was incubated overnight at 4°C, washed 3 times with PBS, added goat anti-rabbit and donkey anti-mouse fluorescent antibodies, incubated for 1 hour, washed 3 times with PBS, and mounted.

[0080] 2. Western Blot to detect the expression of proBDNF

[0081] Take 6 mice in each group, deeply anesthetize the mice, quickly remove the skin, subcutaneous and muscle tissue of the plantar side of the administration side, place them in the tissue lysate that has been pre-cooled on...

Embodiment 2

[0086] A polyclonal antibody to proBDNF attenuates inflammatory pain

[0087] Mature BDNF in the spinal cord is known to be involved in inflammatory and neuropathic pain, and neutralizing increased spinal BDNF attenuates pain processing [8] . Upregulation of local proBDNF following peripheral inflammation suggests that peripheral proBDNF is also involved in inflammatory pain. To test this hypothesis, the inventors first examined whether neutralizing increased proBDNF could attenuate formalin injection-induced inflammatory pain. Formalin injection in the medial plantar usually elicits a biphasic pain response, the first phase begins immediately after formalin injection and lasts for 5 minutes, the second phase begins at 10 minutes after injection and lasts for 40-60 minutes. minute [9] . Polyclonal anti-human proBDNF antibody (poly-Ab-proBDNF) (5ml / kg) can completely block the function of proBDNF [10] , the polyclonal antibody was administered 30 minutes before formalin pl...

Embodiment 3

[0099] Peripheral proBDNF is a pain mediator

[0100] This experiment investigated whether upregulation of proBDNF contributes to pain hypersensitivity. First, the recombinant human proBDNF protein was injected into the sole of the foot, and the paw withdrawal threshold (paw withdrawal threshold, PWT) after the injection was checked. Medial plantar injections of recombinant proBDNF significantly reduced PWT, which was detectable at a dose of 0.1 μg and became more robust at doses of 0.25 μg and 1 μg ( figure 2 D). However, mature BDNF (0.25 μg) had only a marginal effect on PWT ( figure 2 D). These results suggest that peripheral proBDNF, but not mature BDNF, induces mechanical hypersensitivity. To further confirm whether upregulation of proBDNF induces mechanical allodynia, the inventors examined the effect of overexpressing peripheral proBDNF on PWT. An adenoviral vector encoding proBDNF gene and enhanced green fluorescent protein (EGFP) gene (Ad-proBDNF) and a contro...

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Abstract

The invention belongs to the field of biopharmacy and in particular relates to a peripheral brain derived neurotrophic factor (proBDNF) for regulating pain as an inflammatory medium. The invention discloses a binding molecule having neutralization or inhibitory activity on the proBDNF or a signal transmission molecule thereof, and the binding molecule can be used for relieving, inhibiting or treating the pain. A polyclonal antibody neutralizes the proBDNF, and the pain is weakened in different inflammatory pain models.

Description

technical field [0001] The invention belongs to the field of biopharmaceuticals, and relates to peripheral brain-derived neurotrophic factor precursor (proBDNF) as an inflammatory mediator to regulate pain. More specifically, the present invention relates to the use of binding molecules with neutralizing or inhibitory activity on proBDNF or its signaling molecules in the preparation of drugs for alleviating, inhibiting or treating pain. Background technique [0002] Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor that exerts multiple biological roles, including neuronal survival, neuronal formation, and synaptic plasticity [1] . Like other neurotrophic factors, BDNF is initially synthesized as a precursor and subsequently cleaved by proteases to mature BDNF [2-4] . The prodomain of BDNF is critical for the correct folding and secretion pathway of mature BDNF. proBDNF not only serves as an intermediate in the synthesis of mature BDNF, but also binds to i...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K31/7088A61K39/395A61P29/00
Inventor 周菲娜
Owner 周意
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