Mu-Opioid Receptor in the Nucleus Submedius: Involvement in Opioid-Induced Inhibition of Mirror-Image Allodynia in a Rat Model of Neuropathic Pain

Wang, Jun-Yang; Zhao, Mei; Huang, Feifei; Tang, Jing-Shi; Yuan, Yukang

doi:10.1007/s11064-008-9733-6

Cited by 10 publications

(4 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Variation in the development of contralateral hypersensitivity has also been reported in the SNI model [13,14]. It has been proposed that such mirror-image sensitisation may be subject to regulation by endogenous analgesic mechanisms [59], and this suppression can be mimicked by the systemic administration of the α 2 -agonist clonidine [67]. We have extended these findings to show that mirror-image sensitisation can be uncovered by blocking descending NAergic tone indicating that these pontospinal neurons are actively opposing the spread of sensitisation at a spinal level.…”

Section: Discussionmentioning

confidence: 88%

Endogenous analgesic action of the pontospinal noradrenergic system spatially restricts and temporally delays the progression of neuropathic pain following tibial nerve injury

Hughes

Hickey

Hulse

et al. 2013

Pain

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 88%

Endogenous analgesic action of the pontospinal noradrenergic system spatially restricts and temporally delays the progression of neuropathic pain following tibial nerve injury

Hughes

Hickey

Hulse

et al. 2013

Pain

View full text Add to dashboard Cite

show abstract

“…Furthermore, others suggested that supraspinal structures may play important roles in the occurrence of mirror pain. For instance, the opioid receptor signaling in the thalamic submedius and ventromedial nuclei are inhibitory of mirror or contralateral pain whereas the mediodorsal (MD) nucleus, a key relay for spinal nociceptive inputs [ 23 ], facilitates the mirror or contralateral pain [ 6 , 24 , 25 ]. The anterior cingulate cortex (ACC) is a first-order cortical region that responds to painful stimuli [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

Neuroinflammation in the anterior cingulate cortex: the potential supraspinal mechanism underlying the mirror-image pain following motor fiber injury

Chen

Liu

et al. 2022

J Neuroinflammation

View full text Add to dashboard Cite

Background Peripheral nerve inflammation or lesion can affect contralateral healthy structures, and thus result in mirror-image pain. Supraspinal structures play important roles in the occurrence of mirror pain. The anterior cingulate cortex (ACC) is a first-order cortical region that responds to painful stimuli. In the present study, we systematically investigate and compare the neuroimmune changes in the bilateral ACC region using unilateral- (spared nerve injury, SNI) and mirror-(L5 ventral root transection, L5-VRT) pain models, aiming to explore the potential supraspinal neuroimmune mechanism underlying the mirror-image pain. Methods The up-and-down method with von Frey hairs was used to measure the mechanical allodynia. Viral injections for the designer receptors exclusively activated by designer drugs (DREADD) were used to modulate ACC glutamatergic neurons. Immunohistochemistry, immunofluorescence, western blotting, protein microarray were used to detect the regulation of inflammatory signaling. Results Increased expressions of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and chemokine CX3CL1 in ACC induced by unilateral nerve injury were observed on the contralateral side in the SNI group but on the bilateral side in the L5-VRT group, representing a stronger immune response to L5-VRT surgery. In remote ACC, both SNI and L5-VRT induced robust bilateral increase in the protein level of Nav1.6 (SCN8A), a major voltage-gated sodium channel (VGSC) that regulates neuronal activity in the mammalian nervous system. However, the L5-VRT-induced Nav1.6 response occurred at PO 3d, earlier than the SNI-induced one, 7 days after surgery. Modulating ACC glutamatergic neurons via DREADD-Gq or DREADD-Gi greatly changed the ACC CX3CL1 levels and the mechanical paw withdrawal threshold. Neutralization of endogenous ACC CX3CL1 by contralateral anti-CX3CL1 antibody attenuated the induction and the maintenance of mechanical allodynia and eliminated the upregulation of CX3CL1, TNF-α and Nav1.6 protein levels in ACC induced by SNI. Furthermore, contralateral ACC anti-CX3CL1 also inhibited the expression of ipsilateral spinal c-Fos, Iba1, CD11b, TNF-α and IL-6. Conclusions The descending facilitation function mediated by CX3CL1 and its downstream cascade may play a pivotal role, leading to enhanced pain sensitization and even mirror-image pain. Strategies that target chemokine-mediated ACC hyperexcitability may lead to novel therapies for the treatment of neuropathic pain.

show abstract

“…We expected that the nerve injury evoked disappearance of latexin in spinal cord neurons should increase carboxypeptidase A activity and possibly enhance protein breakdown of carboxypeptidase substrate proteins or peptides. Among them are the endogenous opiod leu-enkephalin [32] and endothelin-1 [33] which may impact on the endogenous ability of nociceptive control [34], [35]. Increased cleavage particularly of endogenous opioid peptides might contribute to the development of neuropathic pain.…”

Section: Discussionmentioning

confidence: 99%

Nerve Injury Evoked Loss of Latexin Expression in Spinal Cord Neurons Contributes to the Development of Neuropathic Pain

et al. 2011

View full text Add to dashboard Cite

Nerve injury leads to sensitization mechanisms in the peripheral and central nervous system which involve transcriptional and post-transcriptional modifications in sensory nerves. To assess protein regulations in the spinal cord after injury of the sciatic nerve in the Spared Nerve Injury model (SNI) we performed a proteomic analysis using 2D-difference gel electrophoresis (DIGE) technology. Among approximately 2300 protein spots separated on each gel we detected 55 significantly regulated proteins after SNI whereof 41 were successfully identified by MALDI-TOF MS. Out of the proteins which were regulated in the DIGE analyses after SNI we focused on the carboxypeptidase A inhibitor latexin because protease dysfunctions contribute to the development of neuropathic pain. Latexin protein expression was reduced after SNI which could be confirmed by Western Blot analysis, quantitative RT-PCR and in-situ hybridisation. The decrease of latexin was associated with an increase of the activity of carboxypeptidase A indicating that the balance between latexin and carboxypeptidase A was impaired in the spinal cord after peripheral nerve injury due to a loss of latexin expression in spinal cord neurons. This may contribute to the development of cold allodynia because normalization of neuronal latexin expression in the spinal cord by AAV-mediated latexin transduction or administration of a small molecule carboxypeptidase A inhibitor significantly reduced acetone-evoked nociceptive behavior after SNI. Our results show the usefulness of proteomics as a screening tool to identify novel mechanisms of nerve injury evoked hypernociception and suggest that carboxypeptidase A inhibition might be useful to reduce cold allodynia.

show abstract

Mu-Opioid Receptor in the Nucleus Submedius: Involvement in Opioid-Induced Inhibition of Mirror-Image Allodynia in a Rat Model of Neuropathic Pain

Cited by 10 publications

References 34 publications

Endogenous analgesic action of the pontospinal noradrenergic system spatially restricts and temporally delays the progression of neuropathic pain following tibial nerve injury

Endogenous analgesic action of the pontospinal noradrenergic system spatially restricts and temporally delays the progression of neuropathic pain following tibial nerve injury

Neuroinflammation in the anterior cingulate cortex: the potential supraspinal mechanism underlying the mirror-image pain following motor fiber injury

Nerve Injury Evoked Loss of Latexin Expression in Spinal Cord Neurons Contributes to the Development of Neuropathic Pain

Contact Info

Product

Resources

About