Spontaneous pain in partial nerve injury models of neuropathy and the role of nociceptive sensory cover

Koplovitch, Pini; Minert, Anne; Devor, Marshall

doi:10.1016/j.expneurol.2012.04.005

Cited by 20 publications

(26 citation statements)

References 34 publications

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“…S2 G-I). We also observed that diabetic animals and controls demonstrated a similar degree of autotomy, a behavior considered to be pain-related (43), in the ipsilateral hind paws 1 wk after sciatic nerve transection (Fig. S3).…”

Section: Resultssupporting

confidence: 56%

Coenzyme Q10 prevents peripheral neuropathy and attenuates neuron loss in the db ⁻ /db ⁻ mouse, a type 2 diabetes model

Shi

Zhang

Zeberg³

et al. 2012

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

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Diabetic peripheral neuropathy (DPN) is the most common complication in both type 1 and type 2 diabetes. Here we studied some phenotypic features of a well-established animal model of type 2 diabetes, the leptin receptor-deficient db − /db − mouse, and also the effect of long-term (6 mo) treatment with coenzyme Q10 (CoQ10), an endogenous antioxidant. Diabetic mice at 8 mo of age exhibited loss of sensation, hypoalgesia (an increase in mechanical threshold), and decreases in mechanical hyperalgesia, cold allodynia, and sciatic nerve conduction velocity. All these changes were virtually completely absent after the 6-mo, daily CoQ10 treatment in db − /db − mice when started at 7 wk of age. There was a 33% neuronal loss in the lumbar 5 dorsal root ganglia (DRGs) of the db − /db − mouse versus controls at 8 mo of age, which was significantly attenuated by CoQ10. There was no difference in neuron number in 5/6-wk-old mice between diabetic and control mice. We observed a strong down-regulation of phospholipase C (PLC) β3 in the DRGs of diabetic mice at 8 mo of age, a key molecule in pain signaling, and this effect was also blocked by the 6-mo CoQ10 treatment. Many of the phenotypic, neurochemical regulations encountered in lumbar DRGs in standard models of peripheral nerve injury were not observed in diabetic mice at 8 mo of age. These results suggest that reactive oxygen species and reduced PLCβ3 expression may contribute to the sensory deficits in the late-stage diabetic db − /db − mouse, and that early long-term administration of the antioxidant CoQ10 may represent a promising therapeutic strategy for type 2 diabetes neuropathy.is a debilitating complication of both type 1 and type 2 diabetes, affecting up to 50% of diabetes patients (1-5). DPN can be observed early in human diabetes (6, 7). Early neurophysiological studies indicated that at initial stages of the illness, the severity of the polyneuropathy was similar in type 1 and type 2 diabetes patients (8). However, more recent studies showed distinct differences both in humans and rodent models. Thus, progressive axonal atrophy and loss are more serious in type 1 diabetes, which in contrast to type 2 shows nodal and paranodal degenerative changes, as well as more severe downstream effects on neuroskeletal and adhesive proteins (9).In type 1 and type 2 diabetes, many patients initially experience painful diabetic neuropathy, allodynia, which subsides and then is replaced by loss of sensation, hypoalgesia (5, 10, 11). A similar course of disease has been noted in the db /db− mouse, just one of many animal models of diabetes (SI Text), has since then been extensively studied as a particularly robust model for type 2 DPN (14).Previous studies of mammalian DPN models have reported a decrease in impulse conduction velocity (CV) in several peripheral nerves, interpreted as being caused by a reduction in number of large or medium-sized axons (15-20), demyelination (18,19,(21)(22)(23), or axon shrinkage/atrophy (24, 25). Unmyelinated and myelinated fibers in the skin a...

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Section: Resultssupporting

confidence: 56%

Coenzyme Q10 prevents peripheral neuropathy and attenuates neuron loss in the db ⁻ /db ⁻ mouse, a type 2 diabetes model

Shi

Zhang

Zeberg³

et al. 2012

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

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“…The use of forelimb models in rabbits is more frequent. 45e47 Some models use more than one nerve of the forelimb, 45e47,53 the hindlimb, 17,21,35,38,42 or both. 33 A neuroma model on the facial nerve has also been described, but it is far less popular.…”

Section: Animal Model Animalmentioning

confidence: 99%

“…Some authors combined ligation and transection in a single- 21,23,35 or two-stage model. 17 Ligation alone or crush injuries have been rarely reported 17,28,35 for terminal neuromas, due to their low potential for nerve damage, and to the high nerve regeneration potential of rats. Others reported multiple injuries in different subgroups of animals to investigate the physiopathology of terminal neuromas, 24 or to compare methods for neuroma prevention.…”

Section: Mechanism Of Injurymentioning

confidence: 99%

“…In the study of sensory terminal neuromas, models using the sural and/or saphenous nerve 16,17,23,31 are preferable to the mixed sciatic nerve.…”

Section: Terminal Neuromasmentioning

confidence: 99%

“…A different neuroma model of neuropathic pain was described by Koplovitch et al 17 : they proposed a two-stage injury model on saphenous and sural rat nerves, combining a 'spared nerve injury' (SNI), with a ligation and transection or crush. Different from the classic SNI model, 15 in which autotomy is rare, their model showed that spontaneous dysaesthesias and pain are nonetheless present after an SNI: the SNI has a priming effect, and autotomy appears when sensory sensibility is removed by the second-stage nerve injury.…”

Section: Terminal Neuromasmentioning

confidence: 99%

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A systematic review of animal models for experimental neuroma

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et al. 2015

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Effect of low frequency transcutaneous magnetic stimulation on sensory and motor transmission

Leung

Shukla

Lee

et al. 2015

Bioelectromagnetics

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Peripheral nerve injury diminishes fast conducting large myelinated afferent fibers transmission but enhances smaller pain transmitting fibers firing. This aberrant afferent neuronal behavior contributes to development of chronic post-traumatic peripheral neuropathic pain (PTP-NP). Non-invasive dynamic magnetic flux stimulation has been implicated in treating PTP-NP, a condition currently not adequately addressed by other therapies including transcutaneous electrical nerve stimulation (TENS). The current study assessed the effect of low frequency transcutaneous magnetic stimulation (LFTMS) on peripheral sensory thresholds, nerve conduction properties, and TENS induced fast afferent slowing effect as measured by motor and sensory conduction studies in the ulnar nerve. Results indicated sham LFTMS with TENS (Sham + TENS) significantly (P = 0.02 and 0.007, respectively) reduces sensory conduction velocity (CV) and increases sensory onset latency (OL), and motor peak latency (PL) whereas, real LFTMS with TENS (Real + TENS) reverses effects of TENS on sensory CV and OL, and significantly (P = 0.036) increases the sensory PL. LFTMS alone significantly (P < 0.05) elevates sensory PL and onset-to-peak latency. LFTMS appears to reverse TENS slowing effect on fast conducting fibers and casts a selective peripheral modulatory effect on slow conducting pain afferent fibers.

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Spontaneous pain in partial nerve injury models of neuropathy and the role of nociceptive sensory cover

Cited by 20 publications

References 34 publications

Coenzyme Q10 prevents peripheral neuropathy and attenuates neuron loss in the db ⁻ /db ⁻ mouse, a type 2 diabetes model

Coenzyme Q10 prevents peripheral neuropathy and attenuates neuron loss in the db ⁻ /db ⁻ mouse, a type 2 diabetes model

A systematic review of animal models for experimental neuroma

Effect of low frequency transcutaneous magnetic stimulation on sensory and motor transmission

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Spontaneous pain in partial nerve injury models of neuropathy and the role of nociceptive sensory cover

Cited by 20 publications

References 34 publications

Coenzyme Q10 prevents peripheral neuropathy and attenuates neuron loss in the db − /db − mouse, a type 2 diabetes model

Coenzyme Q10 prevents peripheral neuropathy and attenuates neuron loss in the db − /db − mouse, a type 2 diabetes model

A systematic review of animal models for experimental neuroma

Effect of low frequency transcutaneous magnetic stimulation on sensory and motor transmission

Contact Info

Product

Resources

About

Coenzyme Q10 prevents peripheral neuropathy and attenuates neuron loss in the db ⁻ /db ⁻ mouse, a type 2 diabetes model

Coenzyme Q10 prevents peripheral neuropathy and attenuates neuron loss in the db ⁻ /db ⁻ mouse, a type 2 diabetes model