scholarly journals Toll-Like Receptor 9-Mediated Neuronal Innate Immune Reaction Is Associated with Initiating a Pro-Regenerative State in Neurons of the Dorsal Root Ganglia Non-Associated with Sciatic Nerve Lesion

2021 ◽  
Vol 22 (14) ◽  
pp. 7446
Author(s):  
Petr Dubový ◽  
Ivana Hradilová-Svíženská ◽  
Václav Brázda ◽  
Marek Joukal
Keyword(s):  
Sciatic Nerve ◽  
Nerve Injury ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Immune Reaction ◽  
Innate Immune ◽  
Nerve Lesion ◽  
Toll Like Receptor ◽  
Drg Neurons ◽  
Sciatic Nerve Lesion

One of the changes brought about by Wallerian degeneration distal to nerve injury is disintegration of axonal mitochondria and consequent leakage of mitochondrial DNA (mtDNA)—the natural ligand for the toll-like receptor 9 (TLR9). RT-PCR and immunohistochemical or Western blot analyses were used to detect TLR9 mRNA and protein respectively in the lumbar (L4-L5) and cervical (C7-C8) dorsal root ganglia (DRG) ipsilateral and contralateral to a sterile unilateral sciatic nerve compression or transection. The unilateral sciatic nerve lesions led to bilateral increases in levels of both TLR9 mRNA and protein not only in the lumbar but also in the remote cervical DRG compared with naive or sham-operated controls. This upregulation of TLR9 was linked to activation of the Nuclear Factor kappa B (NFκB) and nuclear translocation of the Signal Transducer and Activator of Transcription 3 (STAT3), implying innate neuronal immune reaction and a pro-regenerative state in uninjured primary sensory neurons of the cervical DRG. The relationship of TLR9 to the induction of a pro-regenerative state in the cervical DRG neurons was confirmed by the shorter lengths of regenerated axons distal to ulnar nerve crush following a previous sciatic nerve lesion and intrathecal chloroquine injection compared with control rats. The results suggest that a systemic innate immune reaction not only triggers the regenerative state of axotomized DRG neurons but also induces a pro-regenerative state further along the neural axis after unilateral nerve injury.

Sympathetic modulation of activity in rat dorsal root ganglion neurons changes over time following peripheral nerve injury

1996 ◽  
Vol 76 (2) ◽  
pp. 753-763 ◽  
Author(s):  
M. Michaelis ◽  
M. Devor ◽  
W. Janig
Keyword(s):  
Sciatic Nerve ◽  
Firing Rate ◽  
Nerve Injury ◽  
Dorsal Root ◽  
Sciatic Nerve Injury ◽  
Dorsal Root Ganglion Neurons ◽  
Nerve Lesion ◽  
Sympathetic Stimulation ◽  
The Mean ◽  
Ganglion Neurons

1. We recorded from centrally connected axons isolated from the proximal stump of the sciatic nerve in intact rats and in rats whose nerves had been transected 4 days-6 mo previously. Afferent axons selected for study had spontaneous impulse activity that originated ectopically in dorsal root ganglia (DRGs) L4 and L5. The sympathetic supply of these DRGs was excited by repetitive electrical stimulation of ventral roots T13 and L1. We examined quantitatively changes in afferent ongoing firing evoked by sympathetic stimulation. Results are based on observations from 161 neurons in rats with sciatic nerve injury and from 58 neurons in control rats with intact sciatic nerves. Of these 219 neurons, 204 had myelinated fibers (A neurons) and 15 had unmyelinated fibers (C neurons), on the basis of measurements of conduction velocity. 2. In rats with nerve injury the majority of the spontaneously active neurons tested (95 of 161) responded to sympathetic stimulation with a change in ongoing firing frequency: 41 neurons exhibited a significant increase in discharge frequency that was often followed by suppression (28 of 41), and 54 neurons responded with a decrease in ongoing activity (simple suppression). In control rats, in contrast, only 1 of the 58 spontaneously active sensory neurons tested responded to sympathetic stimulation. 3. In A neurons, the response pattern changed systematically with time after sciatic nerve injury. At 4-22 days after nerve lesion, excitation was much more common than suppression. At 60-93 days, excitation and suppression occurred about equally. At 110-171 days, suppression was by far the more common response. 4. Of the 14 C neurons, 2 were excited by sympathetic stimulation (at 4-22 days postoperative) and 10 were suppressed (2 at 4-22 days, 8 at > 60 days). The only spontaneously active C neuron found in control rats was not affected by sympathetic stimulation. 5. The magnitude of responses in the three postoperative intervals investigated was similar. This was so for both the excitatory and the simple suppressive responses. The average latency between onset of stimulation and excitatory responses in afferent A fibers (approximately 10 s) was significantly less than the latency to simple suppressive responses (approximately 20 s). 6. The mean spontaneous firing rate of A neurons decreased with time after nerve lesion. No change was observed in C neuron activity. The mean firing rate of A neurons was significantly higher than that of C neurons 4-93 days after nerve lesion, but not later. In all three postoperative periods investigated, the mean rate of spontaneous activity was the same in A neurons that responded to sympathetic stimulation and A neurons that did not. 7. The results show that nerve injury triggers sympathetic-sensory coupling within rat DRGs. Excitatory coupling is preferentially present in the period shortly after nerve injury, and is subsequently replaced by suppressive coupling. This suggests that there is a gradual change in the underlying coupling mechanism.

Identification of differentially expressed genes in dorsal root ganglia following partial sciatic nerve injury

Neuroscience ◽  
1999 ◽  
Vol 95 (4) ◽  
pp. 1111-1120 ◽  
Author(s):  
R.A. Newton ◽  
S. Bingham ◽  
P.D. Davey ◽  
A.D. Medhurst ◽  
V. Piercy ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Nerve Injury ◽  
Differentially Expressed Genes ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Sciatic Nerve Injury ◽  
Differentially Expressed

Case 3

2018 ◽  
Author(s):  
Bashar Katirji
Keyword(s):  
Sciatic Nerve ◽  
Nerve Injury ◽  
Clinical Manifestations ◽  
Sciatic Nerve Injury ◽  
Foot Drop ◽  
Motor Deficits ◽  
Nerve Lesion ◽  
Piriformis Syndrome ◽  
Sciatic Nerve Lesion ◽  
Painful Syndrome

Sciatic nerve injury is a relatively uncommon lower extremity mononeuropathy. The various etiologies of sciatic neuropathies are highlighted in this case. The clinical manifestations and diagnosis include distinguishing foot drop due to sciatic neuropathy from peroneal (fibular) neuropathy across the fibular neck, L5 radiculopathy, and lumbosacral plexopathy. The electrodiagnostic features of sciatic nerve lesion are separated from those of foot drop due to other peripheral nerve causes. In contrast to sciatic nerve injury, the piriformis syndrome is mostly a painful syndrome with no or minimal sensory or motor deficits. The clinical manifestations of piriformis syndrome and controversies surrounding this syndrome completes the discussion in this case.

scholarly journals Metamizole relieves pain by influencing cytokine levels in dorsal root ganglia in a rat model of neuropathic pain

2020 ◽  
Vol 72 (5) ◽  
pp. 1310-1322
Author(s):  
Renata Zajaczkowska ◽  
Klaudia Kwiatkowski ◽  
Katarzyna Pawlik ◽  
Anna Piotrowska ◽  
Ewelina Rojewska ◽  
...  
Keyword(s):  
Nervous System ◽  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Nerve Injury ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Pain Treatment ◽  
Opioid Analgesic ◽  
Intraperitoneal Administration ◽  
Pain Symptoms

Abstract Background Treatment of neuropathic pain is still challenging. Recent studies have suggested that dorsal root ganglia (DRG), which carry sensory neural signals from the peripheral nervous system to the central nervous system, are important for pathological nociception. A proper understanding of the significance and function of DRG and their role in pharmacotherapy can help to improve the treatment of neuropathic pain. Metamizole, also known as sulpyrine or dipyrone, is a non-opioid analgesic commonly used in clinical practice, but it is not used for neuropathic pain treatment. Methods Chronic constriction injury (CCI) of the sciatic nerve was induced in Wistar rats. Metamizole was administered intraperitoneally (ip) preemptively at 16 and 1 h before CCI and then twice a day for 7 days. To evaluate tactile and thermal hypersensitivity, von Frey and cold plate tests were conducted, respectively. Results Our behavioral results provide evidence that repeated intraperitoneal administration of metamizole diminishes the development of neuropathic pain symptoms in rats. Simultaneously, our findings provide evidence that metamizole diminishes the expression of pronociceptive interleukins (IL-1beta, IL-6, and IL-18) and chemokines (CCL2, CCL4, and CCL7) in DRG measured 7 days after sciatic nerve injury. These assays indicate, for the first time, that metamizole exerts antinociceptive effects on nerve injury-induced neuropathic pain at the DRG level. Conclusions Finally, we indicate that metamizole-induced analgesia in neuropathy is associated with silencing of a broad spectrum of cytokines in DRG. Our results also suggest that metamizole is likely to be an effective medication for neuropathic pain. Graphic abstract

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