Neuropeptide Y release in the rat spinal cord measured with Y1 receptor internalization is increased after nerve injury

NEUROPHARMACOLOGY

卷:158

Article

Marvizon, Juan Carlos^1,2  Chen, Wenling^1,2  Fu, Weisi³  Taylor, Bradley K.^3,4,5 

[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Vatche & Tamar Manoukian Div Digest Dis, 900 Vet Ave,Warren Hall Bldg, Los Angeles, CA 90095 USA

[2] Vet Affairs Greater Los Angeles Healthcare Syst, 11310 Wilshire Blvd,Bldg 115, Los Angeles, CA 90073 USA

[3] Univ Kentucky, Med Ctr, Dept Physiol, Lexington, KY USA

[4] Univ Pittsburgh, Dept Anesthesiol & Perioperat Med, Pittsburgh Ctr Pain Res, Pittsburgh, PA USA

[5] Univ Pittsburgh, Pittsburgh Project End Opioid Misuse, Pittsburgh, PA USA

关键词: C-fiber;    Neuropathic pain;    Nociception;    Neurotransmitter release;   

DOI  :  10.1016/j.neuropharm.2019.107732

来源: Elsevier

【 摘 要 】

Neuropeptide Y (NPY) modulates nociception in the spinal cord, but little is known about its mechanisms of release. We measured NPY release in situ using the internalization of its Y1 receptor in dorsal horn neurons. Y1 receptor immunoreactivity was normally localized to the cell surface, but addition of NPY to spinal cord slices increased the number of neurons with Y1 internalization in a biphasic fashion (EC(50)s of 1 nM and 1 mu M). Depolarization with KCl, capsaicin, or the protein kinase A activator 6-benzoyl-cAMP also induced Y1 receptor internalization, presumably by releasing NPY. NMDA receptor activation in the presence of BVT948, an inhibitor of protein tyrosine phosphatases, also released NPY. Electrical stimulation of the dorsal horn frequency-dependently induced NPY release; and this was decreased by the Y1 antagonist BIBO3304, the Nav channel blocker lidocaine, or the Cav2 channel blocker co-conotoxin MVIIC. Dorsal root immersion in capsaicin, but not its electrical stimulation, also induced NPY release. This was blocked by CNQX, suggesting that part of the NPY released by capsaicin was from dorsal horn neurons receiving synapses from primary afferents and not from the afferent themselves. Mechanical stimulation in vivo, with rub or clamp of the hindpaw, elicited robust Y1 receptor internalization in rats with spared nerve injury but not sham surgery. In summary, NPY is released from dorsal horn interneurons or primary afferent terminals by electrical stimulation and by activation of TRPV1, PKA or NMDA receptors in. Furthermore, NPY release evoked by noxious and tactile stimuli increases after peripheral nerve injury.

【 授权许可】

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