A Novel Peripheral Action of PICK1 Inhibition in Inflammatory Pain

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Chronic pain is a major healthcare problem that impacts one in five adults across the globe. Current treatment is compromised by dose-limiting side effects including drowsiness, apathy, fatigue, loss of ability to function socially and professionally as well as a high abuse liability. Most of these side effects result from broad suppression of excitatory neurotransmission. Chronic pain states are associated with specific changes in the efficacy of synaptic transmission in the pain pathways leading to amplification of non-noxious stimuli and spontaneous pain. Consequently, a reversal of these specific changes may pave the way for the development of efficacious pain treatment with fewer side effects. We have recently described a high-affinity, bivalent peptide TAT-P4-(C5)2, enabling efficient targeting of the neuronal scaffold protein, PICK1, a key protein in mediating chronic pain sensitization. In the present study, we demonstrate that in an inflammatory pain model, the peptide does not only relieve mechanical allodynia by targeting PICK1 involved in central sensitization, but also by peripheral actions in the inflamed paw. Further, we assess the effects of the peptide on novelty-induced locomotor activity, abuse liability, and memory performance without identifying significant side effects.

Original languageEnglish
Article number750902
JournalFrontiers in Cellular Neuroscience
Number of pages13
Publication statusPublished - 2021

Bibliographical note

Publisher Copyright:
Copyright © 2021 Jensen, Noes-Holt, Sørensen and Madsen.

    Research areas

  • avidity, bivalent peptide, neuropathic pain, PDZ inhibitor, peptide inhibitor, PICK1 inhibitor

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