PI3Kγ/AKT Signaling in High Molecular Weight Hyaluronan (HMWH)-Induced Anti-Hyperalgesia and Reversal of Nociceptor Sensitization.

ABSTRACT: High molecular weight hyaluronan (HMWH), a well-established treatment for osteoarthritis pain, is anti-hyperalgesic in preclinical models of inflammatory and neuropathic pain. HMWH-induced anti-hyperalgesia is mediated by its action at cluster of differentiation 44 (CD44), the cognate hyaluronan receptor, which can signal via phosphoinositide 3-kinase (PI3K), a large family of kinases involved in diverse cell functions. We demonstrate that intrathecal administration of an oligodeoxynucleotide (ODN) antisense to mRNA for PI3Kγ (a Class I PI3K isoform) expressed in dorsal root ganglia (DRGs), and intradermal administration of a PI3Kγ-selective inhibitor (AS605240), markedly attenuates HMWH-induced anti-prostaglandin E₂ (PGE₂) hyperalgesia, in male and female rats. Intra

SUBMITTER: Bonet IJM 

PROVIDER: S-EPMC8496198 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature