Effect on the peripheral nervous system of systemically administered dimethylsulfoxide in the rat: a neurophysiological and pathological study

Cavaletti, Guido; Oggioni, N; Sala, Federica; Pezzoni, Gabriella; Cavalletti, Ennio; Marmiroli, P; Petruccioli, M G; Frattola, L.; Tredici, G

doi:10.1016/s0378-4274(00)00269-1

Cited by 59 publications

(34 citation statements)

References 11 publications

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“…This delay in axonal regeneration could be due to the effect of DMSO that was used as solvent. Studies have shown that DMSO affects the structure and functions of sciatic nerve in rats [96], and induces apoptosis in the mouse brain [97]. My findings support the results of previous studies, which have shown that nerve injury upregulates LC3 [98,99].…”

Section: Resultssupporting

confidence: 88%

Autophagy in Peripheral Neuropathy

Osman¹

2017

Linköping University Medical Dissertations

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Peripheral neuropathy includes a wide range of diseases affecting millions around the world, and many of these diseases have unknown etiology. Peripheral neuropathy in diabetes represents a large proportion of peripheral neuropathies. Nerve damage can also be caused by trauma. Peripheral neuropathies are a significant clinical problem and efficient treatments are largely lacking. In the case of a transected nerve, different methods have been used to repair or reconstruct the nerve, including the use of nerve conduits, but functional recovery is usually poor. Autophagy, a cellular mechanism that recycles damaged proteins, is impaired in the brain in many neurodegenerative diseases affecting animals and humans. No research, however, has investigated the presence of autophagy in the human peripheral nervous system. In this study, I present the first structural evidence of autophagy in human peripheral nerves. I also show that the density of autophagy structures is higher in peripheral nerves of patients with chronic idiopathic axonal polyneuropathy (CIAP) and inflammatory neuropathy than in controls. The density of these structures increases with the severity of the neuropathy. In animal model, using Goto-Kakizaki (GK) rats with diabetes resembling human type 2 diabetes, activation of autophagy by local administration of rapamycin incorporated in collagen conduits that were used for reconnection of the transected sciatic nerve led to an increase in autophagy proteins LC3 and a decrease in p62 suggesting that the autophagic flux was activated. In addition, immunoreactivity of neurofilaments, which are parts of the cytoskeleton of axons, was increased indicating increased axonal regeneration. I also show that many proteins involved in axonal regeneration and cell survival were up-regulated by rapamycin in the injured sciatic nerve of GK rats four weeks after injury. Taken together, these findings provide new knowledge about the involvement of autophagy in neuropathy and after peripheral nerve injury and reconstruction using collagen conduits. 6 Populärvetenskaplig sammanfattningNervskador (neuropati) orsakade av sjukdomar eller olycksfall påverkar miljontals individer runt om i världen. Nervskador som orsakas av diabetes kallas diabetesneuropati och drabbar varannan patient med diabetes. Neuropati kan också orsakas av kronisk inflammation i nerven eller uppstå utan känd orsak, så kallad kronisk idiopatisk axonal polyneuropati. Patienterna som drabbas av neuropati uppvisar varierande symptom beroende på vilka nerver som drabbas men domningar, stickningar, smärta, känselbortfall och muskelsvaghet finns ofta i symptombilden. Nervskador efter trauma kräver oftast kirurgisk rekonstruktion. För närvarande finns det ingen behandling för diabetesneuropati. Allt fler människor i fysiskt aktiv ålder drabbas av åldersdiabetes (typ 2 diabetes). Detta leder till att fler patienter med diabetes drabbas av traumatiska nervskador som kräver nervreparation. Det är därför viktigt att utveckla reparationsmetoder som fungerar br...

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Section: Resultssupporting

confidence: 88%

Autophagy in Peripheral Neuropathy

Osman¹

2017

Linköping University Medical Dissertations

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“…78 It was also used as a treatment option in osteoarthritis 79 but only with relative efficacy on pain scores. We did not see any effect of DMSO on naïve animal sensitivity behavior regarding toxicity and compared the anti-allodynic of rufinamide with DMSO.…”

Section: Limitations Of the Studymentioning

confidence: 99%

Rufinamide Attenuates Mechanical Allodynia in a Model of Neuropathic Pain in the Mouse and Stabilizes Voltage-gated Sodium Channel Inactivated State

et al. 2013

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Background: Voltage-gated sodium channels dysregulation is important for hyperexcitability leading to pain persistence. Sodium channel blockers currently used to treat neuropathic pain are poorly tolerated. Getting new molecules to clinical use is laborious. We here propose a drug already marketed as anticonvulsant, rufinamide. Methods: We compared the behavioral effect of rufinamide to amitriptyline using the Spared Nerve Injury neuropathic pain model in mice. We compared the effect of rufinamide on sodium currents using in vitro patch clamp in cells expressing the voltage-gated sodium channel Nav1.7 isoform and on dissociated dorsal root ganglion neurons to amitriptyline and mexiletine. Results: In naive mice, amitriptyline (20 mg/kg) increased withdrawal threshold to mechanical stimulation from 1.3 (0.6-1.9) (median [95% CI]) to 2.3 g (2.2-2.5) and latency of withdrawal to heat stimulation from 13.1 (10.4-15.5) to 30.0 s (21.8-31.9), whereas rufinamide had no effect. Rufinamide and amitriptyline alleviated injury-induced mechanical allodynia for 4 h (maximal effect: 0.10 ± 0.03 g (mean ± SD) to 1.99 ± 0.26 g for rufinamide and 0.25 ± 0.22 g to 1.92 ± 0.85 g for amitriptyline). All drugs reduced peak current and stabilized the inactivated state of voltage-gated sodium channel Nav1.7, with similar effects in dorsal root ganglion neurons. Conclusions: At doses alleviating neuropathic pain, amitriptyline showed alteration of behavioral response possibly related to either alteration of basal pain sensitivity or sedative effect or both. Side-effects and drug tolerance/compliance are major problems with drugs such as amitriptyline. Rufinamide seems to have a better tolerability profile and could be a new alternative to explore for the treatment of neuropathic pain. P AIN is essential for survival as it serves as an alert to engage protective behavior. Neuropathic pain, caused by a lesion or disease of the somatosensory nervous system, affects 7% of the population 1 and possesses no protective purpose. Sodium channels are major targets for the development of new drug to treat neuropathic pain.2 Nerve injury changes the expression of sodium channels 3 which affects peripheral nerve hyperexcitability and ectopic discharges along the nerve, in the dorsal root ganglion or at the injury site.4,5 They are composed of a α-pore forming subunit associated to one or two β-modulating subunits. Nine genes encode for the α-subunits, Nav1.1-1.9. Current therapy for neuropathic pain involves adjuvant medications-not primarily developed for this purposesuch as anticonvulsants, antidepressants, or local anesthetics. Address correspondence to Dr. Suter: Pain Center, Department of Anesthesiology, CHUV, Avenue du Bugnon 46, 1011 Lausanne, Switzerland. marc.suter@chuv.ch. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. ANESTHESIOLOGY's articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.

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“…This assay of microtubule dynamics was also able to detect the effects of paclitaxel in sciatic nerves, which are known targets of paclitaxel-induced neuropathy (96). Neuropathy cannot be due to antiproliferative effects, as neurons are postmitotic; rather, it can be attributed directly to the accumulation of aberrantly formed, bundled microtubules that are not part of the normal axonal cytoskeleton (97)(98)(99). In our studies of tubulin dynamics, we observed that paclitaxel caused a net increase in the amount of total and microtubule-associated tubulin, similar to that seen in cultured, drug-treated tumor cells.…”

Section: Fig 6 Effect Of Paclitaxel Dose On Microtubule Dynamics Inmentioning

confidence: 99%

In Vivo Measurement of Microtubule Dynamics Using Stable Isotope Labeling with Heavy Water

Fanara

Turner

Busch

et al. 2004

Journal of Biological Chemistry

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Effect on the peripheral nervous system of systemically administered dimethylsulfoxide in the rat: a neurophysiological and pathological study

Cited by 59 publications

References 11 publications

Autophagy in Peripheral Neuropathy

Autophagy in Peripheral Neuropathy

Rufinamide Attenuates Mechanical Allodynia in a Model of Neuropathic Pain in the Mouse and Stabilizes Voltage-gated Sodium Channel Inactivated State

In Vivo Measurement of Microtubule Dynamics Using Stable Isotope Labeling with Heavy Water

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