The TRPV1 receptor is associated with preferential stress in large dorsal root ganglion neurons in early diabetic sensory neuropathy

Abstract

Chronic diabetic neuropathy is associated with peripheral demyelination and degeneration of nerve fibers. The mechanism(s) underlying neuronal injury in diabetic sensory neuropathy remain poorly understood. Recently, we reported increased expression and function of transient receptor potential vanilloid 1 (TRPV1) in large dorsal root ganglion (DRG) neurons in diabetic sensory neuropathy. In this study, we examined the effects of TRPV1 activation on cell injury pathways in this subpopulation of neurons in the streptozotocin‐induced diabetic rat model. Large DRG neurons from diabetic (6–8 weeks) rats displayed increased oxidative stress and activation of cell injury markers compared with healthy controls. Capsaicin (CAP) treatment induced decreased labeling of MitoTracker Red and increased cytosolic cytochrome c and activation of caspase 3 in large neurons isolated from diabetic rats. CAP treatment also induced oxidative stress in large diabetic DRG neurons, which was blocked by pre‐treatment with caspase or calpain inhibitor. In addition, both μ‐calpain expression and calpain activity were significantly increased in DRG neurons from diabetic rats after CAP treatment. Treatment with capsazepine, a competitive TRPV1 antagonist, markedly reduced these abnormalities in vitro and prevented activation of cell injury in large DRG neurons in diabetic rats in vivo. These results suggest that activation of the TRPV1 receptor activates pathways associated with caspase‐dependent and calpain‐dependent stress in large DRG neurons in STZ‐diabetic rats. Activation of the TRPV1 receptor may contribute to preferential neuronal stress in large DRG neurons relatively early in diabetic sensory neuropathy.

Characterization of Frequency-Dependent Responses of the Vascular System to Repetitive Vibration

“…In models of diabetic neuropathy, there is an increased expression of factors involved in oxidative activity in the DRG, and an increase in oxidative activity has been associated with peripheral nerve death. [29][30][31] Increases in these factors may be because of the activation of local microglia and are associated with the development of neuropathic pain. 32,33 Although we did not directly assess oxidative activity in the DRG, our PCR data from the ganglia are consistent with these findings; exposure to vibration resulted in increases in the expression of platelet activating factor, SOD-1, SOD-2, glutathione synthetase, and glutathione peroxidase in the DRG, and these increases were most prominent in tissue from rats exposed at 250 Hz.…”

Activation of transient receptor potential vanilloid-1 (TRPV1) influences how retinal ganglion cell neurons respond to pressure-related stress

“…[52][53][54][55][56][57][58][59][60][61] The robust Ca 2C conductance associated with TRPV1 activation can also contribute to apoptosis, neurodegenerative disease, and synaptic remodeling. 40,[62][63][64][65][66] TRPV1 also couples to protective cascades. The endogenous cannabinoid anandamide is a ligand for TRPV1 and the cannabinoid type 1 (CB1) receptor and is known to protect against ischemic injury and excitotoxicity.…”

Effects of Gabapentin on Different Neuronal Populations in the Dorsal-Root Ganglia of Rats with Streptozotocin-Induced Diabetes Mellitus

“…The results we obtained in this study agree, to a certain extent, with recent findings indicating that large DRG neurons under conditions of diabetic neuropathy acquire the ability to respond to capsaicin stimulation (capsaicin, an agonist of vanilloid receptors, is responsible for temperature painful sensitivity). In the norm, such sensitivity is typical of exclusively nociceptive neurons [27][28]; i.e., it can be hypothesized that large neurons in diabetic animals function in an abnormal manner. They begin to be involved in the formation of pathological painful sensations.…”