Nociceptive sensitization by the secretory protein Bv8

Area of Science:

• Neuroscience
• Pharmacology
• Molecular Biology

Background:

• Bv8 is a novel secretory protein from amphibian skin, belonging to the conserved Bv8-Prokineticin family.
• Prokineticin receptors (PK-R1, PK-R2) are G-protein coupled receptors involved in various physiological processes.

Purpose of the Study:

• To investigate the physiological effects of Bv8 on nociception in rats.
• To determine the role of prokineticin receptors in mediating Bv8-induced pain sensitization.

Main Methods:

• Intravenous, subcutaneous, and intrathecal injections of Bv8 in rats.
• Topical application of Bv8 to rat paws.
• Analysis of prokineticin receptor expression in dorsal root ganglia (DRG) and dorsal spinal cord (DSC).
• Inhibition assays to determine binding affinities of Bv8 and EG-VEGF to receptors.
• Measurement of intracellular calcium ([Ca2+]i) in DRG neuron cultures.

Main Results:

• Bv8 induced intense systemic and local nociceptive sensitization to mechanical and thermal stimuli.
• Topical Bv8 significantly decreased the nociceptive threshold in the treated paw.
• PK-R1 and PK-R2 were expressed in rat DRG and DSC, binding Bv8 and EG-VEGF with high affinity.
• Bv8 dose-dependently increased intracellular calcium in small diameter DRG neurons.

Conclusions:

• Bv8 acts as a potent nociceptive sensitizer in rats.
• Bv8 exerts its effects by binding to PK receptors in the DSC and primary sensitive neurons.
• This study identifies a novel role for Bv8 in pain modulation and highlights its potential as a target for pain management.