Opioid receptors inhibit the spinal AMPA receptor Ca2+ permeability that mediates latent pain sensitization.

Opioid receptors inhibit the spinal AMPA receptor Ca2+ permeability that mediates latent pain sensitization. Exp Neurol. 2019 Jan 17;: Authors: Taylor BK, Sinha GP, Donahue RR, Grachen CM, Morón JA, Doolen S Abstract Acute inflammation induces sensitization of nociceptive neurons and triggers the accumulation of calcium permeable (CP) α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) in the dorsal horn of the spinal cord. This coincides with behavioral signs of acute inflammatory pain, but whether CP-AMPARs contribute to chronic pain remains unclear. To evaluate this question, we first constructed current-voltage (IV) curves of C-fiber stimulus-evoked, AMPAR-mediated EPSCs in lamina II to test for inward rectification, a key characteristic of CP-AMPARs. We found that the intraplantar injection of complete Freund's adjuvant (CFA) induced an inward rectification at 3 d that persisted to 21 d after injury. Furthermore, the CP- AMPAR antagonist IEM-1460 (50 μM) inhibited AMPAR-evoked Ca2+ transients 21d after injury but had no effect in uninflamed mice. We then used a model of long-lasting vulnerability for chronic pain that is determined by the balance between latent central sensitization (LCS) and mu opioid receptor constitutive activity (MORCA). When administered 21 d after the intraplantar injection of CFA, intrathecal administration of the MORCA inverse agonist naltrexone (NTX, 1 μg, i.t.) reinst...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research