Editorial: Mechanisms and New Targets for the Treatment of Chronic Pain

Nieto, Francisco R.; Vučković, Sonja; Prostran, Milica

doi:10.3389/fphar.2020.600037

Cited by 4 publications

(3 citation statements)

References 23 publications

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“…These findings suggest that pazopanib inhibits the activation of NGF signaling in joint synovium, DRG sensory neurons and suppresses spinal glial activity by arresting the VEGF/VEGFR1-NFκB signaling axis, which is correlated with OA joint pain. In addition, other studies showed direct nociceptive effects of VEGFA/VEGFR1 signaling by modulating the trafficking of TRPV1, which subsequently sensitizes transducers of heat, pressure, or chemical stimuli in nociceptive terminals 13 , 14 , 54 . VEGFR1 activates diverse kinases, such as PLCγ (PLCG1), PI3K, and SRC kinase, that sensitize transducers of heat, pressure, and chemical stimuli in nociceptive terminals, such as those expressing TRPV1 13 .…”

Section: Discussionmentioning

confidence: 99%

Targeting Vascular Endothelial Growth Factor Receptors as a Therapeutic Strategy for Osteoarthritis and Associated Pain

Singh

Wang

et al. 2023

Int. J. Biol. Sci.

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Pain is the major reason that patients suffering from osteoarthritis (OA) seek medical care. We found that vascular endothelial growth factors (VEGFs) mediate signaling in OA pain pathways. To determine the specific contributions of VEGFs and their receptors (VEGFRs) to joint pathology and pain transmission during OA progression, we studied intra-articular (IA) injections of VEGF ligands into murine knee joints. Only VEGF ligands specific for the activation of VEGFR1, but not VEGFR2, induced allodynia within 30 min. Interventions in OA by inhibitors of VEGFRs were done in vivo using a preclinical murine OA model by IA injections of selective inhibitors of VEGFR1/VEGFR2 kinase (pazopanib) or VEGFR2 kinase (vandetanib). OA phenotypes were evaluated using pain-associated murine behavioral tests and histopathologic analyses. Alterations in VEGF/VEGFR signaling by drugs were determined in knee joints, dorsal root ganglia, and spinal cord by immunofluorescence microscopy. Pazopanib immediately relieved OA pain by interfering with pain transmission pathways. Pain reduction by vandetanib was mainly due to the inhibition of cartilage degeneration by suppressing VEGFR2 expression. In conclusion, IA administration of pazopanib, which simultaneously inhibits VEGFR1 and VEGFR2, can be developed as an ideal OA disease-modifying drug that rapidly reduces joint pain and simultaneously inhibits cartilage degeneration.

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Section: Discussionmentioning

confidence: 99%

Targeting Vascular Endothelial Growth Factor Receptors as a Therapeutic Strategy for Osteoarthritis and Associated Pain

Singh

Wang

et al. 2023

Int. J. Biol. Sci.

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“…Adaptations in the nervous system [69] have been shown to occur at a supraspinal level [7,29] but also at a spinal level, since muscle pain, mediated by muscle afferents, could alter the muscle spindle discharge and its effect on the motoneuron pool [39]. Therefore, in conditions of pain [33], the H reflex in superficial muscles that have muscle spindles [60] has already been used to give information regarding spinal neurophysiological changes in excitability [5,9,72], pain modulation [31], and integration of peripheral information [9]. The association between the trapezius muscle and musculoskeletal conditions, such as shoulder pain [31], motivated the present study, which compared trapezius spinal excitability between asymptomatic subjects and symptomatic subjects with chronic shoulder pain [58].…”

Section: Discussionmentioning

confidence: 99%

Differences in Trapezius Muscle H-Reflex between Asymptomatic Subjects and Symptomatic Shoulder Pain Subjects

Melo

Taylor

Ferreira

et al. 2023

Sensors

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In chronic shoulder pain, adaptations in the nervous system such as in motoneuron excitability, could contribute to impairments in scapular muscles, perpetuation and recurrence of pain and reduced improvements during rehabilitation. The present cross-sectional study aims to compare trapezius neural excitability between symptomatic and asymptomatic subjects. In 12 participants with chronic shoulder pain (symptomatic group) and 12 without shoulder pain (asymptomatic group), the H reflex was evoked in all trapezius muscle parts, through C3/4 nerve stimulation, and the M-wave through accessory nerve stimulation. The current intensity to evoke the maximum H reflex, the latency and the maximum peak-to-peak amplitude of both the H reflex and M-wave, as well as the ratio between these two variables, were calculated. The percentage of responses was considered. Overall, M-waves were elicited in most participants, while the H reflex was elicited only in 58–75% or in 42–58% of the asymptomatic and symptomatic participants, respectively. A comparison between groups revealed that the symptomatic group presented a smaller maximum H reflex as a percentage of M-wave from upper trapezius and longer maximal H reflex latency from the lower trapezius (p < 0.05). Subjects with chronic shoulder pain present changes in trapezius H reflex parameters, highlighting the need to consider trapezius neuromuscular control in these individuals’ rehabilitation.

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“…Continuous or on-demand local inhibition of enzymes and receptors in the joint and vertebral bodies reducing sensitization and/or activation of sensory neurons located in or in close proximity to the degenerating joint/discs, has the potential to provide major benefits for pain management. Local inhibition will allow for more precise targeting of the receptors than systemic treatments, which could in turn increase efficacy and reduce adverse side effects [152]. Figure 4.1 shows the difference in systemic vs the desired c0ntrolled drug delivery.…”

Section: Zeroing In On the Medical Problemmentioning

confidence: 99%

Bioelectronic Devices for Targeted Drug Delivery and Monitoring of Microbial Electrogenesis

Roy

2023

Linköping Studies in Science and Technology. Dissertations

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Editorial: Mechanisms and New Targets for the Treatment of Chronic Pain

Cited by 4 publications

References 23 publications

Targeting Vascular Endothelial Growth Factor Receptors as a Therapeutic Strategy for Osteoarthritis and Associated Pain

Targeting Vascular Endothelial Growth Factor Receptors as a Therapeutic Strategy for Osteoarthritis and Associated Pain

Differences in Trapezius Muscle H-Reflex between Asymptomatic Subjects and Symptomatic Shoulder Pain Subjects

Bioelectronic Devices for Targeted Drug Delivery and Monitoring of Microbial Electrogenesis

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