Induction of the unfolded protein response and cell death pathway in Alzheimer's disease, but not in aged Tg2576 mice.

The endoplasmic reticulum (ER) stress results from disrupted protein folding triggered by protein mutation or oxidation, reduced proteasome activity, and altered Ca2+ homeostasis. ER stress is accompanied by activation of the unfolded protein response (UPR) and cell death pathway. We examined if the UPR and cell death pathway would be activated in Alzheimer's disease (AD).

Activation of transcription factor c-jun in dorsal root ganglia induces VIP and NPY upregulation and contributes to the pathogenesis of neuropathic pain.

Vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) in dorsal root ganglia (DRGs) are known to be upregulated and to contribute to the mechanisms of neuropathic pain following peripheral nerve injury. Moreover, transcription factor c-Jun regulates the expressions of both VIP and NPY in cultured DRG neurons. To elucidate the role of c-Jun in the induction of neuropathic pain hypersensitivity, we examined whether activated c-Jun affects pain behavior and the expressions of VIP and NPY following chronic constriction injury (CCI) of rat sciatic nerve.

Temporal expression of cytokines and their receptors mRNAs in a neuropathic pain model.

Proinflammatory mediators, such as tumor necrosis factor (TNF) alpha, interleukin (IL)-1beta and IL-6 have been found to play a key role in the propagation of persistent pain states. We investigated the temporal expressions of the mRNAs and the receptor mRNAs of TNFalpha, IL-1beta and IL-6 in rat dorsal root ganglia and spinal cord in a chronic constriction injury model of neuropathic pain. Our results show that the maximal induction of IL-6 mRNA occurred later and was more sustained than those of TNFalpha and IL-1beta mRNAs in the dorsal root ganglia and spinal cord following chronic injury.

Spinal NF-kB activation induces COX-2 upregulation and contributes to inflammatory pain hypersensitivity.

Cyclooxygenase-2 (COX-2) is a major contributor to the elevation of spinal prostaglandin E2, which augments the processing of nociceptive stimuli following peripheral inflammation, and dynorphin has been shown to have an important role in acute and chronic pain states. Moreover, the transcription factor, nuclear factor-kappa B (NF-kB), regulates the expressions of both COX-2 and dynorphin. To elucidate the role of spinal NF-kB in the induction of inflammatory pain hypersensitivity, we examined whether activated NF-kB affects pain behavior and the expressions of the mRNAs of COX-2 and prodynorphin following peripheral inflammation.