Hypoalgesia and altered inflammatory responses in mice lacking kinin B1 receptors

PNAS, 2000 · DOI: 10.1073/pnas.120035997 · Published: July 5, 2000

Simple Explanation

Kinins are mediators in cardiovascular homeostasis, inflammation, and nociception. This study focuses on the kinin B1 receptor, which is inducible by inflammatory mediators. The researchers generated mice lacking the B1 receptor to understand its function. Mice lacking the B1 receptor showed reduced lipopolysaccharide-induced hypotension and decreased accumulation of leukocytes in inflamed tissue. They also exhibited analgesic behavior in tests of chemical and thermal nociception, suggesting the B1 receptor's role in inflammatory responses and pain modulation. The study suggests that the kinin B1 receptor plays a key role in initiating inflammatory responses and modulating spinal cord plasticity related to pain. This makes it a potential target for treating inflammatory disorders and pain.

Study Duration

Not specified

Participants

Mice with targeted deletion of the gene for the B1 receptor

Evidence Level

Level 2: Experimental study in animals

Key Findings

1
B1 receptor-deficient mice exhibited blunted hypotensive response to bacterial lipopolysaccharide.
2
In B1 receptor-deficient mice, polymorphonuclear leukocyte accumulation was reduced in inflamed tissue.
3
B1 receptor-deficient mice showed hypoalgesia in behavioral tests of chemical and thermal nociception.

Research Summary

The study investigates the physiological function of the kinin B1 receptor by generating mice with a targeted deletion of the B1 receptor gene. These mice are healthy and normotensive but show a blunted hypotensive response to bacterial lipopolysaccharide. B1 receptor-deficient mice exhibit reduced accumulation of polymorphonuclear leukocytes in inflamed tissue and demonstrate hypoalgesia in behavioral tests of chemical and thermal nociception, indicating the B1 receptor's involvement in inflammatory responses and pain modulation. The research concludes that the kinin B1 receptor plays a crucial role in initiating inflammatory responses and modulating spinal cord plasticity, suggesting it as a useful pharmacological target for treating inflammatory disorders and pain.

Practical Implications

Therapeutic Target for Inflammatory Disorders

The B1 receptor is a potential pharmacological target for the treatment of inflammatory disorders due to its role in leukocyte accumulation.

Analgesic Drug Development

B1 receptor antagonists may have therapeutic potential as analgesic drugs, especially for pain associated with inflammation.

Understanding Spinal Cord Plasticity

The B1 receptor's role in modulating spinal cord plasticity provides insights into the central component of pain and potential therapeutic interventions.

Study Limitations

1
The study was conducted on mice, and results may not directly translate to humans.
2
The precise mechanisms of B1 receptor action in the spinal cord require further investigation.
3
The study focused on acute inflammatory responses; the role of B1 receptors in chronic inflammation needs further exploration.

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