Peripheral inflammatory injury alters the relative abundance of Gα subunits in the dorsal horn of the spinal cord and in the rostral ventromedial medulla of male rats

Abstract

A diverse array of G protein-coupled receptors (GPCRs) is implicated in the modulation of nociception. The efficacy and potency of several GPCR agonists change as a consequence of peripheral inflammatory injury. Whether these changes reflect alterations in expression of the G proteins themselves is not known. This study examined the expression of transcripts and proteins for the α subunits of three classes of heteromeric G proteins in the dorsal horn of the spinal cord and the rostral ventromedial medulla (RVM) of male rats four days and two weeks after intraplantar injection of complete Freund’s adjuvant (CFA) or saline. Levels of Gα transcript in the dorsal horn or RVM were unchanged by CFA treatment. However, in the dorsal horn, Gαi protein decreased in cytosolic and membrane fractions four days after CFA treatment. Levels of Gαz protein decreased in the membrane fraction. Levels of the other Gα subunits did not differ. Levels of the Gα subunits were unchanged two weeks after CFA treatment. In the RVM, Gαz protein levels decreased in the cytosolic fraction four days after CFA treatment. No other differences were observed. Two weeks after CFA, the levels for all Gα subunits trended higher in the RVM. These data indicate that peripheral inflammatory injury induces subtle changes in the abundance of Gα subunits that is specific with respect to class, subcellular compartment, tissue, and time after injury. These changes have the potential to alter the balance of the different subcellular signaling pathways through which GPCR agonists act to modulate nociception.

Age-Induced Changes in µ-Opioid Receptor Signaling in the Midbrain Periaqueductal Gray of Male and Female Rats

“…Specifically, CFA treated rats had reduced EC50 values, regardless of age or sex. Reductions in Gα subunit expression have also been reported within both the rostral ventromedial medulla and spinal cord dorsal horn following intraplantar CFA in adult male rats (Wattiez et al, 2017). The mechanism whereby persistent inflammatory pain would impact G-protein activation, and not the other pharmacodynamics of MOR, is not known.…”