Inflammation enhances Y1 receptor signaling, neuropeptide Y-mediated inhibition of hyperalgesia, and substance P release from primary afferent neurons

  title={Inflammation enhances Y1 receptor signaling, neuropeptide Y-mediated inhibition of hyperalgesia, and substance P release from primary afferent neurons},
  author={Bradley K. Taylor and Wen Fu and K. E. Kuphal and C-O. Stiller and Michelle K Winter and W. Chen and Gregory Corder and Janice H. Urban and Kenneth E. McCarson and Juan Carlos Marviz{\'o}n},

Facilitation of neuropathic pain by the NPY Y1 receptor-expressing subpopulation of excitatory interneurons in the dorsal horn

It is concluded that Y1R-expressing excitatory dorsal horn interneurons facilitate neuropathic pain hypersensitivity, and this neuronal population remains sensitive to intrathecal NPY after nerve injury.

[Effects of blockade of 5-HT2A receptors in inflammatory site on complete Freund's adjuvant-induced chronic hyperalgesia and neuropeptide Y expression in the spinal dorsal horn in rats].

The present study suggests that the peripheral 5-HT2A receptors can be a promising target for pharmaceutical therapy to treat chronic inflammatory pain without central nervous system side effects.

An NPY Y1 receptor antagonist unmasks latent sensitization and reveals the contribution of Protein Kinase A and EPAC to chronic inflammatory pain.

PKA and Epac are sufficient to maintain long-lasting latent sensitization of dorsal horn neurons that is kept in remission by the NPY-Y1 receptor system, and two novel molecular signaling pathways in the dorsal horn that drive latent sensitized in the setting of chronic inflammatory pain are identified.

NPY2R signaling gates spontaneous and mechanical, but not thermal, pain transmission

The results suggest that Y1R could be a therapeutic target that may be exploited for alleviating spontaneous pain without affecting acute pain transmission and highlight the pivotal role of endogenous Y2R in gating mechanical and spontaneous pain transmission.



Neurokinin 1 Receptor Internalization in Spinal Cord Slices Induced by Dorsal Root Stimulation Is Mediated by NMDA Receptors

The NK1R antagonist L-703,606 abolished the internalization produced by 100 Hz stimulation or NMDA, and the release of SP in the dorsal horn appears to be controlled by NMDA receptors.

Inflammation Increases the Distribution of Dorsal Horn Neurons That Internalize the Neurokinin-1 Receptor in Response to Noxious and Non-Noxious Stimulation

Comparisons of mechanical and thermal stimulation in normal rats and in rats with persistent hindpaw inflammation provide a new perspective on the reorganization of dorsal horn circuits in the setting of persistent injury and demonstrate a critical contribution of SP.

Cannabinoid CB1 receptor facilitation of substance P release in the rat spinal cord, measured as neurokinin 1 receptor internalization

The inhibition by AM251 of NK1 receptor internalization was reversed by antagonists of μ‐opioid and GABAB receptors, indicating that CB1 receptors facilitate substance’P release by inhibiting the release of GABA and opioids next to primary afferent terminals, producing disinhibition.

Substance P release in the dorsal horn assessed by receptor internalization: NMDA receptors counteract a tonic inhibition by GABAB receptors

It is demonstrated that GABAB receptors, but not GABAA or glycine receptors, inhibit substance P release induced by dorsal root stimulation, and in its absence SP release no longer requires NMDA receptor activation.

NMDA-receptor regulation of substance P release from primary afferent nociceptors

It is reported that activation of the NMDA receptor causes release of substance P, a peptide neurotransmitter made by small-diameter, primary, sensory 'pain' fibres, and suggested that presynaptic NMDA receptors located on the terminals of small-Diameter pain fibres facilitate and prolong the transmission of nociceptive messages, through the release of Substance P and glutamate.

Tonic inhibition of chronic pain by neuropeptide Y

Spinal NPY receptor systems are established as an endogenous braking mechanism that exerts a tonic, long-lasting, broad-spectrum inhibitory control of spinal nociceptive transmission, thus impeding the transition from acute to chronic pain.

Spinal Opioid Analgesia: How Critical Is the Regulation of Substance P Signaling?

The results suggest that opioid analgesia predominantly involves postsynaptic inhibitory mechanisms and/or presynaptic control of non-SP-containing primary afferent nociceptors.