From SARS-CoV-2 to analgesia: harnessing the VEGF-A/NRP-1 axis for pain therapy

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11120%2F23%3A43925065" target="_blank" >RIV/00216208:11120/23:43925065 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1097/j.pain.0000000000002851" target="_blank" >https://doi.org/10.1097/j.pain.0000000000002851</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1097/j.pain.0000000000002851" target="_blank" >10.1097/j.pain.0000000000002851</a>

Jazyk výsledku

angličtina

Název v původním jazyce

From SARS-CoV-2 to analgesia: harnessing the VEGF-A/NRP-1 axis for pain therapy

Popis výsledku v původním jazyce

Vascular endothelial growth factor (VEGF) encompasses a family of secreted proteins primarily implicated in the control of angiogenesis during growth and development. The VEGF family consists of 5 members with VEGF-A being by far the most widely studied. VEGF-A signals though 2 different tyrosine kinase receptors (VEGFR1 and VEGFR2) and 2 neuropilin coreceptors (NRP-1 and NRP-2) that enhance the affinity of VEGF-A for VEGFRs.1 It is well established that alteration of the VEGF system is causally linked to a plethora of angiogenic-related diseases such as arthritis, diabetes, and cancer that often are associated with the concomitant development of the chronic pain condition. For instance, in a patient with osteoarthritis, elevation of VEGF levels in synovial fluids is associated with higher pain scores24 that is reversed on inhibition of VEGF signaling.9 The association between the VEGF system and pain is further supported by numerous rodent studies. For instance, blockade of VEGFR alleviate inflammatory pain in an experimental model of rheumatoid arthrosis.3,4 Moreover, blockade of the VEGF system mediates analgesia in several experimental models of neuropathic pain,11-14,20,25 an effect that is reported to be mediated by the normalization of the expression levels of pronociceptive P2X2/3 receptors or TRPA1/TRPV1 channels in primary afferent nociceptive fibers. Finally, several experimental studies reported the benefit of blocking the VEGF system as a mean to alleviate cancer pain7,10,22 or chemotherapy-induced pain.6,18 Although the VEGF system has received increased attention for its role in nociception, most research has centered around the importance of VEGF/VEGFRs axis, and little is known about the role of NRP in nociception. Recently, a study from the Khanna laboratory reported that binding of SARS-CoV-2 spike protein onto NRP-1 disrupts spinal VEGF-A/NRP-1 (Fig. 1) signaling and reverse mechanical allodynia in a preclinical rodent model of spared nerve injury (SNI).19 These findings not only exposed a molecular stratagem by which SARS-CoV-2 can hijack the nociceptive nervous system, but also uncovered a previously unrecognized potentially druggable target for the treatment of pain.

Název v anglickém jazyce

From SARS-CoV-2 to analgesia: harnessing the VEGF-A/NRP-1 axis for pain therapy

Popis výsledku anglicky

Vascular endothelial growth factor (VEGF) encompasses a family of secreted proteins primarily implicated in the control of angiogenesis during growth and development. The VEGF family consists of 5 members with VEGF-A being by far the most widely studied. VEGF-A signals though 2 different tyrosine kinase receptors (VEGFR1 and VEGFR2) and 2 neuropilin coreceptors (NRP-1 and NRP-2) that enhance the affinity of VEGF-A for VEGFRs.1 It is well established that alteration of the VEGF system is causally linked to a plethora of angiogenic-related diseases such as arthritis, diabetes, and cancer that often are associated with the concomitant development of the chronic pain condition. For instance, in a patient with osteoarthritis, elevation of VEGF levels in synovial fluids is associated with higher pain scores24 that is reversed on inhibition of VEGF signaling.9 The association between the VEGF system and pain is further supported by numerous rodent studies. For instance, blockade of VEGFR alleviate inflammatory pain in an experimental model of rheumatoid arthrosis.3,4 Moreover, blockade of the VEGF system mediates analgesia in several experimental models of neuropathic pain,11-14,20,25 an effect that is reported to be mediated by the normalization of the expression levels of pronociceptive P2X2/3 receptors or TRPA1/TRPV1 channels in primary afferent nociceptive fibers. Finally, several experimental studies reported the benefit of blocking the VEGF system as a mean to alleviate cancer pain7,10,22 or chemotherapy-induced pain.6,18 Although the VEGF system has received increased attention for its role in nociception, most research has centered around the importance of VEGF/VEGFRs axis, and little is known about the role of NRP in nociception. Recently, a study from the Khanna laboratory reported that binding of SARS-CoV-2 spike protein onto NRP-1 disrupts spinal VEGF-A/NRP-1 (Fig. 1) signaling and reverse mechanical allodynia in a preclinical rodent model of spared nerve injury (SNI).19 These findings not only exposed a molecular stratagem by which SARS-CoV-2 can hijack the nociceptive nervous system, but also uncovered a previously unrecognized potentially druggable target for the treatment of pain.

Druh

O - Ostatní výsledky

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů