Article

Examining Synaptic AMPA Receptor Trafficking and its Effects

Recent research has shown that changes in AMPA receptor subunit trafficking in the dorsal horn may be driven by peripheral inflammatory insults.

There’s a growing body of evidence that suggests spinal AMPA receptor subunit trafficking change is associated with central sensitization in inflammatory pain. Recent research has shown that changes in AMPA receptor subunit trafficking in the dorsal horn may be driven by peripheral inflammatory insults.

In the study of inflammatory pain, examining whether this connection is accurate can increase the understanding of the cause of pain hypersensitivity.

Three studies included in the Synaptic AMPAvReceptor Trafficking in Inflammatory Pain symposium, featured at APS’ 28th Annual Scientific Conference, presented recent research that focused on AMPA recpeptors and their role in pain manifestation:

AMPA receptors are involved in acute spinal processing of nociceptive and non-nociceptive inputs in the dorsal horn, and play a role in spinal central sensitization in persistent pain.

Maxx Larson, PhD, a postdoctoral fellow at the University of Oslo, presented research on the effect of peripheral inflammatory insults on the changes in synaptic AMPA receptor subunit trafficking in dorsal horn neurons. Larson primary focused on GluA1 and GluA2-containing AMPA receptors, peptidergic and nonpeptidergic, in a presentation titled, “The Hindpaw capsaicin model of acute inflammatory pain.” Among his chief points of discussion where that: GluA1-containing AMPA receptors are recruited are recruited to non-peptidergic C fiber synapses; few or no GluA1 or GluA2/3-containing AMPA receptors are recruited to peptidergic nociceptive synapses; and peptiderfic synapses may instead be pointed via CaMKII-mediated receptor phosphorylation. (CaMKII is an enzyme involved in hippocampal LTP.)

Linda Sorkin, PhD, Physiology, presented information on nocicpetive inflammation-induced protein phophorylation of the serine residues in AMPA receptor subunits and its role. Sorkin’s presentation focused on paw carrageenan and TNF Mediated changes in AMPA signaling. Data demonstrated that “TNF derived from astrocytes induces insertion of Ca2 permeable AMPA receptors into plasma membranes of hippocampal neurons within minutes.” With this result, Sorkin and her team hypothesized that: “Spinal TNF derived from glia also causes fast insertion of Ca2 permeable AMPAr into dorsal horn pain neurons via a multi-step definable pathway. This change induces sensitized pain behavior.”

Dr. Yuan-Xiang Tao, presented work that demonstrated how the prevention of changes in synaptic AMPA receptor trafficking in dorsal horn impairs pain hypersensitivity in inflammatory pain. Tao focused on a study to evaluate whether synaptic expression of GluR2 changed in dorsal horn neurons under chronic inflammatory pain conditions. The study used CFA injection versus saline injection to measure results. Chief findings were that: CFA injection produces long-term mechanical pain; CFA does not alter total expression of GluR1 and GluR2 in the dorsal horn; and CFA injection does not change the distribution of GluR1 and Glur2.

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