Targeting the VEGF-A/Neuropilin 1 axis for relief of neuropathic pain

Pain, 2023 · DOI: 10.1097/j.pain.0000000000002850 · Published: July 1, 2023

Simple Explanation

Chronic pain is a significant issue with limited effective and safe treatments. Opioids, a common treatment, have many side effects. This research explores a new target: the interaction between VEGF-A and Neuropilin 1 (NRP1), which appears to play a role in pain signaling. The study identified a compound, NRP1–4, that blocks VEGF-A from binding to NRP1. They found that NRP1–4 reduced pain-related signals in nerve cells and decreased pain behavior in animal models. The researchers conclude that targeting the VEGF-A/NRP1 interaction with compounds like NRP1–4 could lead to new, non-opioid pain medications.

Study Duration

Not specified

Participants

Adult male and female Sprague-Dawley rats (100–250 g) and rat pups (postnatal 10–15 days)

Evidence Level

Not specified

Key Findings

1
NRP1–4 blocks the increase in excitability of sensory neurons caused by VEGF-A, suggesting it interferes with VEGF-A's action on these neurons.
2
NRP1–4 reduces sodium and N-type calcium currents in sensory neurons, which are critical for transmitting pain signals.
3
Both central (spinal) and systemic (intravenous) administration of NRP1–4 can reverse neuropathic pain in rat models.

Research Summary

The study identifies the VEGF-A/NRP1 interaction as a potential target for pain relief. Blocking this interaction with the compound NRP1-4 decreases sensory neuron excitability. NRP1-4 reduces pain-related ion currents and normalizes spinal neurotransmission. It also reverses experimental neuropathic pain in preclinical models. The research suggests that NRP1-4 is a promising lead compound for developing new analgesics. It targets the NRP1/VEGF-R2 complex.

Practical Implications

Drug Development

NRP1-4 could be the basis for a new class of non-opioid pain medications.

Targeted Therapy

Targeting the VEGF-A/NRP1 complex offers a more specific approach to pain management.

Clinical Trials

Further research is needed to assess the safety and efficacy of NRP1-4 in humans.

Study Limitations

1
DRG recordings included nerve growth factor (NGF) in the culture media, this might be affecting VEGF-A concentration
2
Our approach utilizes an alternative strategy to achieve specificity, by targeting the VEGF-A co-receptor, NRP1, which co-localizes with VEGF-A in a narrow range of tissues
3
NRP1 is expressed on blood vessels, it is possible that targeting this receptor could result in some vascular complications.

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