Dorsal root ganglion neurons show increased expression of the calcium channel α2δ-1 subunit following partial sciatic nerve injury

Newton, R.; Bingham, Sharon; Case, Patrick; Sanger, Gareth J.; Lawson, Sally N.

doi:10.1016/s0169-328x(01)00188-7

Cited by 211 publications

(155 citation statements)

References 30 publications

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“…115,116 The expression of the α 2 δ-1 subunit has been shown to increase in chronic pain states, as well as in both afferent sensory neurons and in the spinal cord dorsal horn in experimental neuropathic pain models. 117,118 This correlates well with the observation that gabapentin exerts analgesic properties primarily in sensitized or hyperalgesic states. 119,120,121 More recently gabapentin and pregabalin have been used clinically in humans to treat a variety of neuropathic pain states and early post-surgical pain, often but not always with success.…”

Section: Non-conventional Systemic Analgesics With Anti-hyperalgesic supporting

confidence: 77%

Neuropathic Pain Management in Chronic Laminitis

Driessen

Bauquier

Zarucco

2010

Veterinary Clinics of North America: Equine Practice

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Section: Non-conventional Systemic Analgesics With Anti-hyperalgesic supporting

confidence: 77%

Neuropathic Pain Management in Chronic Laminitis

Driessen

Bauquier

Zarucco

2010

Veterinary Clinics of North America: Equine Practice

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“…expression of 4 genes [Gadd45a (15), ATF3 (16,17), SmagP (18), and Cacna2d1 (19,20)] whose expression is altered by nerve injury, using RNA from the dorsal root ganglia of animals that received nerve blocks (n ϭ 4 in each group). As a positive control for local anesthetic-associated nerve injury that would be relevant to the formulations used here, 4 animals were given sciatic nerve blocks with 80 mM amitriptyline, a tricyclic antidepressant with local anesthetic properties that resembles bupivacaine in structure and mechanism of action (21), and that causes severe myotoxicity and neurotoxicity (22,23).…”

Section: Resultsmentioning

confidence: 99%

Prolonged duration local anesthesia with minimal toxicity

Epstein-Barash

Shichor

Kwon

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

144

154

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Injectable local anesthetics that would last for many days could have a marked impact on periprocedural care and pain management. Formulations have often been limited in duration of action, or by systemic toxicity, local tissue toxicity from local anesthetics, and inflammation. To address those issues, we developed liposomal formulations of saxitoxin (STX), a compound with ultrapotent local anesthetic properties but little or no cytotoxicity. In vitro, the release of bupivacaine and STX from liposomes depended on the lipid composition and on whether dexamethasone was incorporated. In cell culture, bupivacaine, but not STX, was myotoxic (to C2C12 cells) and neurotoxic (to PC12 cells) in a concentration- and time-dependent manner. Liposomal formulations containing combinations of the above compounds produced sciatic nerve blockade lasting up to 7.5 days (with STX + dexamethasone liposomes) in male Sprague–Dawley rats. Systemic toxicity only occurred where high loadings of dexamethasone increased the release of liposomal STX. Mild myotoxicity was only seen in formulations containing bupivacaine. There was no nerve injury on Epon-embedded sections, and these liposomes did not up-regulate the expression of 4 genes associated with nerve injury in the dorsal root ganglia. These results suggest that controlled release of STX and similar compounds can provide very prolonged nerve blocks with minimal systemic and local toxicity.

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“…In several different animal models of neuropathic pain caused by peripheral nerve damage, there are many genes, including ion channels, whose expression is altered in injured dorsal root ganglion (DRG) neurons (Wang et al, 2002;Ji and Strichartz, 2004). In particular, there is an upregulation of the calcium channel auxiliary subunit ␣ 2 ␦-1 (Newton et al, 2001;Wang et al, 2002). A corresponding increase in expression of ␣ 2 ␦-1 protein is observed in both the affected ganglia and the spinal cord dorsal horn Bauer et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

α₂δ-1 Gene Deletion Affects Somatosensory Neuron Function and Delays Mechanical Hypersensitivity in Response to Peripheral Nerve Damage

et al. 2013

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The ␣ 2 ␦-1 subunitofvoltage-gatedcalciumchannelsisupregulatedaftersensorynerveinjuryandisalsothetherapeutictargetofgabapentinoid drugs. It is therefore likely to play a key role in the development of neuropathic pain. In this study, we have examined mice in which ␣ 2 ␦-1 gene expression is disrupted, to determine whether ␣ 2 ␦-1 is involved in various modalities of nociception, and for the development of behavioral hypersensitivity after partial sciatic nerve ligation (PSNL). We find that naive ␣ 2 ␦-1 Ϫ/Ϫ mice show a marked behavioral deficit in mechanical and cold sensitivity, but no change in thermal nociception threshold. The lower mechanical sensitivity is mirrored by a reduced in vivo electrophysiological response of dorsal horn wide dynamic range neurons. The Ca V 2.2 level is reduced in brain and spinal cord synaptosomes from ␣ 2 ␦-1 Ϫ/Ϫ mice, and ␣ 2 ␦-1 Ϫ/Ϫ DRG neurons exhibit lower calcium channel current density. Furthermore, a significantly smaller number of DRG neurons respond to the TRPM8 agonist menthol. After PSNL, ␣ 2 ␦-1 Ϫ/Ϫ mice show delayed mechanical hypersensitivity, which only develops at 11 d after surgery, whereas in wild-type littermates it is maximal at the earliest time point measured (3 d). There is no compensatory upregulation of ␣ 2 ␦-2 or ␣ 2 ␦-3 after PSNL in ␣ 2 ␦-1 Ϫ/Ϫ mice, and other transcripts, including neuropeptide Y and activating transcription factor-3, are upregulated normally. Furthermore, the ability of pregabalin to alleviate mechanical hypersensitivity is lost in PSNL ␣ 2 ␦-1 Ϫ/Ϫ mice. Thus, ␣ 2 ␦-1 is essential for rapid development of mechanical hypersensitivity in a nerve injury model of neuropathic pain.

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Dorsal root ganglion neurons show increased expression of the calcium channel α2δ-1 subunit following partial sciatic nerve injury

Cited by 211 publications

References 30 publications

Neuropathic Pain Management in Chronic Laminitis

Neuropathic Pain Management in Chronic Laminitis

Prolonged duration local anesthesia with minimal toxicity

α₂δ-1 Gene Deletion Affects Somatosensory Neuron Function and Delays Mechanical Hypersensitivity in Response to Peripheral Nerve Damage

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Dorsal root ganglion neurons show increased expression of the calcium channel α2δ-1 subunit following partial sciatic nerve injury

Cited by 211 publications

References 30 publications

Neuropathic Pain Management in Chronic Laminitis

Neuropathic Pain Management in Chronic Laminitis

Prolonged duration local anesthesia with minimal toxicity

α2δ-1 Gene Deletion Affects Somatosensory Neuron Function and Delays Mechanical Hypersensitivity in Response to Peripheral Nerve Damage

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Product

Resources

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α₂δ-1 Gene Deletion Affects Somatosensory Neuron Function and Delays Mechanical Hypersensitivity in Response to Peripheral Nerve Damage