A potential anti-allodynic mechanism of GDNF following L5 spinal nerve ligation; Mitigation of NPY up-regulation in the touch sense pathway

Fukuoka, Tetsuo; Noguchi, Koichi

doi:10.1016/j.neuroscience.2015.07.059

Cited by 7 publications

(9 citation statements)

References 35 publications

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“…Moreover, NaV 1.8 channels were over-expressed in Large Sensorial Cells after L5-L6 root ligation (Fukuoka & Noguchi, 2015). All these findings likely represent the adaptive ability of this TTX-R channel, in order to cope with different stimulations and modulate its activity.…”

Section: Nociceptors Plastic Propertiesmentioning

confidence: 82%

“…NaV 1.8 is involved in different adaptive and neuroplasticity‐related mechanisms on which light has been shed with NaV 1.8 gene knock‐out models: different investigations detected a marked hyperalgesia after nociceptive stimulation in mice (Dong, Sun, Lu, Wang, & Wu, ); also, if a Chronic Constriction Injury (CCI) was provoked in mice, mRNA alteration and protein rearrangement were observed in cells (Wang, Wang, et al, ). Moreover, NaV 1.8 channels were over‐expressed in Large Sensorial Cells after L5‐L6 root ligation (Fukuoka & Noguchi, ). All these findings likely represent the adaptive ability of this TTX‐R channel, in order to cope with different stimulations and modulate its activity.…”

Section: Gdnf and Voltage Gated Sodium Channelsmentioning

confidence: 99%

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Nociceptor plasticity: A closer look

Pace

Passavanti

Nardis

et al. 2017

Journal Cellular Physiology

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Nociceptors are receptors specifically involved in detecting a tissue damage and transducing it in an electrical signal. Nociceptor activation provoked by any kind of acute lesion is related to the release of several mediators of inflammation, within the framework of a process defined as "peripheral sensitization." This results in an exaggerated response to the painful stimulus, clinically defined as "primary hyperalgesia." The concept of "neuroplasticity" may explain the adaptive mechanisms carried out by the Nervous System in relation to a "harmful" damage; also, neuroplasticity mechanisms are also fundamental for rehabilitative intervention protocols. Here we review several studies that addressed the role of different receptors and ionic channels discovered on nociceptor surface and their role in pain perception. The changes in expression, distribution, and functioning of receptors and ionic channels are thought to be a part of the neuroplasticity property, through which the Nervous System constantly adapts to external stimuli. Moreover, some of the reviewed mediators are also been associated to "central sensitization," a process that results in pain chronicization when the painful stimulation is particularly prolonged or intense, and lastly leads to the memorization of the uncomfortable painful perception.

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Section: Nociceptors Plastic Propertiesmentioning

confidence: 82%

Section: Gdnf and Voltage Gated Sodium Channelsmentioning

confidence: 99%

Nociceptor plasticity: A closer look

Pace

Passavanti

Nardis

et al. 2017

Journal Cellular Physiology

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“…This GDNF dose has also been used in previous studies, 3,12,13 and our protocol successfully reversed established mechanical allodynia on day 10. 14 Additionally, we used a smaller pump (model #1007D; 0.5 µl/h, 7 days; Alzet) containing GDNF or saline ( n = 7, each) for the electrophysiological study using the smaller rats. We always use adult rats (210–240 g) for behavioral and histochemical studies.…”

Section: Methodsmentioning

confidence: 99%

Spinal glial cell line-derived neurotrophic factor infusion reverses reduction of Kv4.1-mediated A-type potassium currents of injured myelinated primary afferent neurons in a neuropathic pain model

Shinoda

Fukuoka

Takeda³

et al. 2019

Mol Pain

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High frequency spontaneous activity in injured primary afferents has been proposed as a pathological mechanism of neuropathic pain following nerve injury. Although spinal infusion of glial cell line-derived neurotrophic factor reduces the activity of injured myelinated A-fiber neurons after fifth lumbar (L5) spinal nerve ligation in rats, the implicated molecular mechanism remains undetermined. The fast-inactivating transient A-type potassium current (I A ) is an important determinant of neuronal excitability, and five voltage-gated potassium channel (Kv) alpha-subunits, Kv1.4, Kv3.4, Kv4.1, Kv4.2, and Kv4.3, display I A in heterologous expression systems. Here, we examined the effect of spinal glial cell line-derived neurotrophic factor infusion on I A and the expression of these five Kv mRNAs in injured A-fiber neurons using the in vitro patch clamp technique and in situ hybridization histochemistry. Glial cell line-derived neurotrophic factor infusion reversed axotomy-induced reduction of the rheobase, elongation of first spike duration, and depolarization of the resting membrane potential. L5 spinal nerve ligation significantly reduced the current density of I A and glial cell line-derived neurotrophic factor treatment reversed the reduction. Among the examined Kv mRNAs, only the change in Kv4.1-expression was parallel with the change in I A after spinal nerve ligation and glial cell line-derived neurotrophic factor treatment. These findings suggest that glial cell line-derived neurotrophic factor should reduce the hyperexcitability of injured A-fiber primary afferents by I A recurrence. Among the five I A -related Kv channels, Kv4.1 should be a key channel, which account for this I A recurrence.

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“…In injury-based models of experimental neuropathies, GDNF and ARTN prevented and reversed tactile and thermal hypersensitivity, and normalized the expression of various sensory neuron markers. GDNF was also shown to normalize electrophysiological properties of injured sensory neurons and the expression of sodium channels (Bennett et al 1998 ; Boucher et al 2000 ; Boucher and McMahon 2001 ; Wang et al 2003 , 2014 , 2017 ; Hao et al 2003 ; Gardell et al 2003 ; Zwick et al 2003 ; Pezet et al 2006 ; Sakai et al 2008 ; Hubbard et al 2008 ; Takasu et al 2011 ; Fukuoka and Noguchi 2015 ). In addition, intraperitoneally injected ARTN relieved herpes virus-induced mechanical hypersensitivity (Asano et al 2006 ).…”

Section: Gfls In Neuropathic Painmentioning

confidence: 99%

Glial cell line-derived neurotrophic factors (GFLs) and small molecules targeting RET receptor for the treatment of pain and Parkinson’s disease

Mahato

Sidorova

2020

Cell Tissue Res

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Rearranged during transfection (RET), in complex with glial cell line-derived (GDNF) family receptor alpha (GFRα), is the canonical signaling receptor for GDNF family ligands (GFLs) expressed in both central and peripheral parts of the nervous system and also in non-neuronal tissues. RET-dependent signaling elicited by GFLs has an important role in the development, maintenance and survival of dopamine and sensory neurons. Both Parkinson’s disease and neuropathic pain are devastating disorders without an available cure, and at the moment are only treated symptomatically. GFLs have been studied extensively in animal models of Parkinson’s disease and neuropathic pain with remarkable outcomes. However, clinical trials with recombinant or viral vector-encoded GFL proteins have produced inconclusive results. GFL proteins are not drug-like; they have poor pharmacokinetic properties and activate multiple receptors. Targeting RET and/or GFRα with small molecules may resolve the problems associated with using GFLs as drugs and can result in the development of therapeutics for disease-modifying treatments against Parkinson’s disease and neuropathic pain.

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A potential anti-allodynic mechanism of GDNF following L5 spinal nerve ligation; Mitigation of NPY up-regulation in the touch sense pathway

Cited by 7 publications

References 35 publications

Nociceptor plasticity: A closer look

Nociceptor plasticity: A closer look

Spinal glial cell line-derived neurotrophic factor infusion reverses reduction of Kv4.1-mediated A-type potassium currents of injured myelinated primary afferent neurons in a neuropathic pain model

Glial cell line-derived neurotrophic factors (GFLs) and small molecules targeting RET receptor for the treatment of pain and Parkinson’s disease

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