Expression of p-Akt in Sensory Neurons and Spinal Cord after Peripheral Nerve Injury

Abstract

Akt has been implicated in pro-survival and anti-apoptotic activities in many cell types, including dorsal root ganglion (DRG) and spinal motor neurons. In this immunohistochemical study we have monitored phosphorylated Akt (p-Akt) levels in adult mouse DRGs and spinal cord following unilateral peripheral sciatic nerve transection (axotomy) or carrageenan-induced inflammation. In control animals around half of the lumbar DRG neuron profiles (NPs), mainly small and medium-sized ones, were p-Akt immunoreactive (IR), and of these around 50% expressed calcitonin gene-related peptide and/or isolectin IB4. Two weeks after axotomy, the number of p-Akt-positive NPs was only slightly reduced, but p-Akt immunofluorescence intensity was strongly increased. One third of the ipsilateral p-Akt-IR NPs was galanin positive, but virtually without colocalization with neuropeptide Y. Furthermore, p-Akt-like immunoreactivity significantly increased in intensity in the ipsilateral spinal dorsal horn after axotomy and expanded into deeper layers. Carrageenan-induced peripheral inflammation increased the number of p-Akt-IR NPs after 1 h. Both axotomy and inflammation caused a clear increase in nuclear p-Akt-like immunoreactivity in DRG neurons. Our findings support a role for Akt as a key signaling molecule in sensory neurons and spinal cord after peripheral injury.

Role for pAKT in rat urinary bladder with cyclophosphamide (CYP)-induced cystitis

“…Numerous studies have demonstrated activation of AKT in DRG and spinal cord neurons following peripheral nerve injury or inflammation (26,58,59,60,71). In the present study, neither AKT nor pAKT was observed in the suburothelial nerve plexus of control or CYP-treated bladder whole mounts.…”

“…For example, basal AKT phosphorylation is present in rodent lumbosacral dorsal root ganglia (DRG) (58,59) and superficial laminae of the spinal cord (26,60) and significantly increases following peripheral nerve injury or inflammation (26,58,59,60,71). Additionally, colocalization of pAKT with markers of unmyelinated, pain-transducing C-fibers such as IB4, TrkA, calcitonin gene-related peptide (CGRP), and transient potential vanilloid-1 channel (TRPV1) (58,59,71,74) has been demonstrated. Specific inhibitors of AKT signaling including deguelin, AKT Inhibitor IV, SH-6, or NL-71-101 can attenuate mechanical hyperalgesia resulting from intradermal hindpaw capsaicin injection (59,60) or sciatic nerve ligation (71), suggesting a nociceptive role for AKT signaling in peripheral inflammation or injury.…”

“…Recent studies have demonstrated additional roles for activated (phosphorylated; p) AKT in the initiation and maintenance of neuropathic pain and visceral inflammation (53,59,60,71). Immunohistochemical techniques demonstrate AKT activation in pain transducing C-fiber primary afferents and dorsal horn neurons following peripheral neuronal injury or tissue inflammation (26,58,59,60,71). In visceral inflammation, pAKT levels increase in the spinal cord dorsal horn following chemically induced colitis (53).…”

Activation of mammalian target of rapamycin contributes to pain nociception induced in rats by BmK I, a sodium channel-specific modulator

“…administration of rapamycin in the formalin test [40] . Moreover, the upstream molecules PI3K and Akt are strongly increased in DRG neurons after peripheral injury [42,43] . Inhibition of this signaling prevented pain behaviors, implying that the PI3K-Akt-mTOR cascade is essential for pain behaviors.…”

Atividade da proteína quinase dependente de RNA (PKR) no sistema nociceptivo em um modelo experimental de neuropatia periférica de origem viral

“…O aumento da fosforilação de Akt também acontece em GRD após a injeção intradérmica de capsaicina in vivo (SUN et al, 2006) e quando a capsaicina também é aplicada in vitro em GRD (ZHUANG et al, 2004), como também há aumento da fosforilação de Akt em GRD de animais após a injeção intraplantar de carragenina (SHI et al, 2009). …”