Streptozocin-Induced Neuropathy Is Associated with Altered Expression of Voltage-Gated Calcium Channel Subunit mRNAs in Rat Dorsal Root Ganglion Neurones

Yusaf, Shahnaz P.; Goodman, James; González, Isabel Martín; Bramwell, S.; Pinnock, R.D.; Dixon, A. R.; Lee, Kevin

doi:10.1006/bbrc.2001.5943

Cited by 47 publications

(32 citation statements)

References 17 publications

(17 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Others have recently reported increased mRNA levels for the ␣ 2 ␦-1 subunit in the DRG of diabetic rats (Yusaf et al, 2001a), but in the present studies, any increase in mRNA expression did not result in a detectable increase of the protein. Although both DB and VIN have been shown to impede retrograde axonal transport (Jakobsen et al, 1981;Macfarlane et al, 1997), there is neither complete loss of retrograde transport mechanisms nor a specific lesion site in the nerve in either model.…”

Section: Discussioncontrasting

confidence: 89%

Injury Type-Specific Calcium Channel α₂δ-1 Subunit Up-Regulation in Rat Neuropathic Pain Models Correlates with Antiallodynic Effects of Gabapentin

Luo

Calcutt

Higuera

et al. 2002

J Pharmacol Exp Ther

357

270

View full text Add to dashboard Cite

The calcium channel ␣ 2 ␦-1 subunit is a structural subunit important for functional calcium channel assembly. In vitro studies have shown that this subunit is the binding site for gabapentin, an anticonvulsant that exerts antihyperalgesic effects by unknown mechanisms. Increased expression of this subunit in the spinal cord and dorsal root ganglia (DRG) has been suggested to play a role in enhanced nociceptive responses of spinal nerve-injured rats to innocuous mechanical stimulation (allodynia). To investigate whether a common mechanism underlies allodynic states derived from different etiologies, and if so, whether similar ␣ 2 ␦-1 subunit up-regulation correlates with these allodynic states, we compared DRG and spinal cord ␣ 2 ␦-1 subunit levels and gabapentin sensitivity in allodynic rats with mechanical nerve injuries (sciatic nerve chronic constriction injury, spinal nerve transection, or ligation), a metabolic disorder (diabetes), or chemical neuropathy (vincristine neurotoxicity). Our data indicated that even though allodynia occurred in all types of nerve injury investigated, DRG and/or spinal cord ␣ 2 ␦-1 subunit up-regulation and gabapentin sensitivity only coexisted in the mechanical and diabetic neuropathies. Thus, induction of the ␣ 2 ␦-1 subunit in the DRG and spinal cord is likely regulated by factors that are specific for individual neuropathies and may contribute to gabapentin-sensitive allodynia. However, the calcium channel ␣ 2 ␦-1 subunit is not the sole molecular change that uniformly characterizes the neuropathic pain states.Peripheral nerve injury can lead to a neuropathic pain state, termed tactile allodynia, in which innocuous tactile stimulation elicits pain behavior. Spinal administration of gabapentin, a novel anticonvulsant that binds to the ␣ 2

show abstract

Section: Discussioncontrasting

confidence: 89%

Injury Type-Specific Calcium Channel α₂δ-1 Subunit Up-Regulation in Rat Neuropathic Pain Models Correlates with Antiallodynic Effects of Gabapentin

Luo

Calcutt

Higuera

et al. 2002

J Pharmacol Exp Ther

357

270

View full text Add to dashboard Cite

show abstract

“…After SNL, we found that the elevation of ␣ 2 ␦-1 protein in DRGs occurs throughout the cytoplasm in all DRG cell subtypes, as also shown for ␣ 2 ␦-1 mRNA after partial sciatic nerve injury (Newton et al, 2001) and in diabetic neuropathy (Yusaf et al, 2001). However, in contrast to mRNA levels, the detection and quantification of ␣ 2 ␦-1 protein provides a more functional assessment.…”

Section: Discussionsupporting

confidence: 57%

The Increased Trafficking of the Calcium Channel Subunit α₂δ-1 to Presynaptic Terminals in Neuropathic Pain Is Inhibited by the α₂δ Ligand Pregabalin

Bauer

Nieto-Rostro²,

Rahman³

et al. 2009

J. Neurosci.

380

378

View full text Add to dashboard Cite

Neuropathic pain results from damage to the peripheral sensory nervous system, which may have a number of causes. The calcium channel subunit ␣ 2 ␦-1 is upregulated in dorsal root ganglion (DRG) neurons in several animal models of neuropathic pain, and this is causally related to the onset of allodynia, in which a non-noxious stimulus becomes painful. The therapeutic drugs gabapentin and pregabalin (PGB), which are both ␣ 2 ␦ ligands, have antiallodynic effects, but their mechanism of action has remained elusive. To investigate this, we used an in vivo rat model of neuropathy, unilateral lumbar spinal nerve ligation (SNL), to characterize the distribution of ␣ 2 ␦-1 in DRG neurons, both at the light-and electron-microscopic level. We found that, on the side of the ligation, ␣ 2 ␦-1 was increased in the endoplasmic reticulum of DRG somata, in intracellular vesicular structures within their axons, and in the plasma membrane of their presynaptic terminals in superficial layers of the dorsal horn. Chronic PGB treatment of SNL animals, at a dose that alleviated allodynia, markedly reduced the elevation of ␣ 2 ␦-1 in the spinal cord and ascending axon tracts. In contrast, it had no effect on the upregulation of ␣ 2 ␦-1 mRNA and protein in DRGs. In vitro, PGB reduced plasma membrane expression of ␣ 2 ␦-1 without affecting endocytosis. We conclude that the antiallodynic effect of PGB in vivo is associated with impaired anterograde trafficking of ␣ 2 ␦-1, resulting in its decrease in presynaptic terminals, which would reduce neurotransmitter release and spinal sensitization, an important factor in the maintenance of neuropathic pain.

show abstract

“…There are some reports suggesting the underlying mechanisms of hyperalgesia in this model 13,[20][21][22][23] . In one of the mechanisms, expression of VR1 are observed in capsaicin-insensitive A-fiber DRG neurons of STZ diabetic mice suggested as a cause of the hyperalgesia.…”

Section: Discussionmentioning

confidence: 73%

Histopathological Changes of Streptozotocin-induced Painful Diabetes and Antihyperalgesic Effect of Capsaicin Cream in Rats

et al. 2008

View full text Add to dashboard Cite

Abstract:To investigate the association between streptozotocin (STZ)-induced painful diabetic neuropathy and the antihyperalgesic effect of capsaicin cream in rats, we first examined the antihyperalgesic effect of capsaicin cream and subsequently performed peripheral neurohistochemical examinations of neuropathic rats. Mechanical hyperalgesia occurred 2 weeks after STZ injection and persisted for 8 weeks of testing. The neuropathy was alleviated by a single application of 0.1% capsaicin cream, but not by cream base. The hyperalgesia did not decrease when the capsaicin cream was applied to normal animals. On the other hand, for dorsal root ganglion (DRG) neurons and hind paw cutaneous nerves, the neurohistochemical examination showed no difference between STZ rats and control rats with capsaicin (vanilloid) receptor subtype 1 (VR1) and NF200 double immunohistochemical staining of DRG neurons, but an increase in A-fibers was seen in the hind paw cutaneous nerves of the STZ rats compared to the control rats. Neither STZ rats nor control rats were toxically affected by the single application of 0.1% capsaicin cream. These results suggest that a single application of capsaicin cream exerts an antihyperalgesic effect in rats with painful neuropathy and increases peripheral A-fibers. However, we could not clarify how VR1 was involved in the effect in rats with STZ painful diabetic neuropathy. (J Toxicol Pathol 2008; 21: 97-104)

show abstract

Streptozocin-Induced Neuropathy Is Associated with Altered Expression of Voltage-Gated Calcium Channel Subunit mRNAs in Rat Dorsal Root Ganglion Neurones

Cited by 47 publications

References 17 publications

Injury Type-Specific Calcium Channel α₂δ-1 Subunit Up-Regulation in Rat Neuropathic Pain Models Correlates with Antiallodynic Effects of Gabapentin

Injury Type-Specific Calcium Channel α₂δ-1 Subunit Up-Regulation in Rat Neuropathic Pain Models Correlates with Antiallodynic Effects of Gabapentin

The Increased Trafficking of the Calcium Channel Subunit α₂δ-1 to Presynaptic Terminals in Neuropathic Pain Is Inhibited by the α₂δ Ligand Pregabalin

Histopathological Changes of Streptozotocin-induced Painful Diabetes and Antihyperalgesic Effect of Capsaicin Cream in Rats

Contact Info

Product

Resources

About

Streptozocin-Induced Neuropathy Is Associated with Altered Expression of Voltage-Gated Calcium Channel Subunit mRNAs in Rat Dorsal Root Ganglion Neurones

Cited by 47 publications

References 17 publications

Injury Type-Specific Calcium Channel α2δ-1 Subunit Up-Regulation in Rat Neuropathic Pain Models Correlates with Antiallodynic Effects of Gabapentin

Injury Type-Specific Calcium Channel α2δ-1 Subunit Up-Regulation in Rat Neuropathic Pain Models Correlates with Antiallodynic Effects of Gabapentin

The Increased Trafficking of the Calcium Channel Subunit α2δ-1 to Presynaptic Terminals in Neuropathic Pain Is Inhibited by the α2δ Ligand Pregabalin

Histopathological Changes of Streptozotocin-induced Painful Diabetes and Antihyperalgesic Effect of Capsaicin Cream in Rats

Contact Info

Product

Resources

About

Injury Type-Specific Calcium Channel α₂δ-1 Subunit Up-Regulation in Rat Neuropathic Pain Models Correlates with Antiallodynic Effects of Gabapentin

Injury Type-Specific Calcium Channel α₂δ-1 Subunit Up-Regulation in Rat Neuropathic Pain Models Correlates with Antiallodynic Effects of Gabapentin

The Increased Trafficking of the Calcium Channel Subunit α₂δ-1 to Presynaptic Terminals in Neuropathic Pain Is Inhibited by the α₂δ Ligand Pregabalin