scholarly journals Peripheral Glutamate Receptors Are Required for Hyperalgesia Induced by Capsaicin

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
You-Hong Jin ◽  
Motohide Takemura ◽  
Akira Furuyama ◽  
Norifumi Yonehara
Keyword(s):  
Spinal Cord ◽  
Glutamate Receptors ◽  
Dorsal Horn ◽  
Transient Receptor Potential ◽  
Small Diameter ◽  
Spinal Cord Dorsal Horn ◽  
Group I ◽  
Nociceptive Responses ◽  
Spinal Cord Dorsal ◽  
Fos Expression

Transient receptor potential vanilloid1 (TRPV1) and glutamate receptors (GluRs) are located in small diameter primary afferent neurons (nociceptors), and it was speculated that glutamate released in the peripheral tissue in response to activation of TRPV1 might activate nociceptors retrogradely. But, it was not clear which types of GluRs are functioning in the nociceptive sensory transmission. In the present study, we examined the c-Fos expression in spinal cord dorsal horn following injection of drugs associated with glutamate receptors with/without capsaicin into the hindpaw. The subcutaneous injection of capsaicin or glutamate remarkably evoked c-Fos expression in ipsilateral sides of spinal cord dorsal horn. This capsaicin evoked increase of c-Fos expression was significantly prevented by concomitant administration of MK801, CNQX, and CPCCOEt. On the other hand, there were not any significant changes in coinjection of capsaicin and MCCG or MSOP. These results reveal that the activation of iGluRs and group I mGluR in peripheral afferent nerves play an important role in mechanisms whereby capsaicin evokes/maintains nociceptive responses.

Comparison of the Effects of Treatment with Intrathecal Lidocaine Given before and after Formalin on Both Nociception and Fos Expression in the Spinal Cord Dorsal Horn 

1998 ◽  
Vol 88 (1) ◽  
pp. 157-164 ◽  
Author(s):  
Kiran Yashpal ◽  
Patrick Mason ◽  
John E. McKenna ◽  
Sushil K. Sharma ◽  
James L. Henry ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Intrathecal Injection ◽  
Post Treatment ◽  
Spinal Cord Dorsal Horn ◽  
Formalin Injection ◽  
Second Phase ◽  
Nociceptive Responses ◽  
Spinal Cord Dorsal ◽  
Fos Expression

Background It has been proposed that the measure of noxious stimulus-induced Fos (the protein product of the immediate early gene c-fos) expression in the spinal cord dorsal horn of laboratory animals may provide an estimate of the potential of specific treatments to produce preemptive analgesia. The present study examined this hypothesis by comparing the effects of intrathecal lidocaine given before and after hindpaw formalin injection on persistent nociceptive responses and Fos expression in spinal cord dorsal horn of rats. Methods Formalin-induced nociception and Fos expression in the spinal cord, in response to a 50-microl injection of 2.5% formalin into the hind paw, were assessed in rats given an intrathecal injection of 50 microl 2% lidocaine by lumbar puncture between the L5 and L6 vertebrae, either 3 min before (pretreatment) or 5 min after (post-treatment) formalin injection. Results Pain behaviors (hindpaw licking, elevation, and favoring) in the second phase of the formalin test were significantly reduced by pretreatment, but were unaffected by post-treatment. The number of immunocytochemically stained Fos-positive cells and the immunoprecipitation of the Fos antibodies were reduced by pretreatment, and were also reduced, to a lesser extent, by post-treatment. Conclusions The finding that persistent nociceptive behaviors and Fos expression were suppressed by intrathecal lidocaine pretreatment suggests that nociception in the second phase of the formalin test depends on increases in central hyperexcitability generated during the first phase. On the other hand, the finding that the intrathecal injection of lidocaine after formalin treatment reduced Fos expression but not nociceptive responses indicates an uncoupling of the behavioral and Fos protein responses to formalin and suggests that changes in Fos expression may not be a good predictor of the ability of agents to produce preemptive analgesia.

scholarly journals Chemokine CCL2 prevents opioid-induced inhibition of nociceptive synaptic transmission in spinal cord dorsal horn

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Mario Heles ◽  
Petra Mrozkova ◽  
Dominika Sulcova ◽  
Pavel Adamek ◽  
Diana Spicarova ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Synaptic Transmission ◽  
Dorsal Horn ◽  
Transient Receptor Potential ◽  
Pain Treatment ◽  
Spinal Cord Dorsal Horn ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Receptors ◽  
Spinal Cord Dorsal

Abstract Background Opioid analgesics remain widely used for pain treatment despite the related serious side effects. Some of those, such as opioid tolerance and opioid-induced hyperalgesia may be at least partially due to modulation of opioid receptors (OR) function at nociceptive synapses in the spinal cord dorsal horn. It was suggested that increased release of different chemokines under pathological conditions may play a role in this process. The goal of this study was to investigate the crosstalk between the µOR, transient receptor potential vanilloid 1 (TRPV1) receptor and C–C motif ligand 2 (CCL2) chemokine and the involvement of spinal microglia in the modulation of opioid analgesia. Methods Patch-clamp recordings of miniature excitatory postsynaptic currents (mEPSCs) and dorsal root evoked currents (eEPSC) in spinal cord slices superficial dorsal horn neurons were used to evaluate the effect of µOR agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO), CCL2, TRPV1 antagonist SB366791 and minocycline. Paw withdrawal test to thermal stimuli was combined with intrathecal (i.t.) delivery of CCL2 and DAMGO to investigate the modulation in vivo. Results Application of DAMGO induced a rapid decrease of mEPSC frequency and eEPSC amplitude, followed by a delayed increase of the eESPC amplitude, which was prevented by SB366791. Chemokine CCL2 treatment significantly diminished all the DAMGO-induced changes. Minocycline treatment prevented the CCL2 effects on the DAMGO-induced eEPSC depression, while mEPSC changes were unaffected. In behavioral experiments, i.t. injection of CCL2 completely blocked DAMGO-induced thermal hypoalgesia and intraperitoneal pre-treatment with minocycline prevented the CCL2 effect. Conclusions Our results indicate that opioid-induced inhibition of the excitatory synaptic transmission could be severely attenuated by increased CCL2 levels most likely through a microglia activation-dependent mechanism. Delayed potentiation of neurotransmission after µOR activation is dependent on TRPV1 receptors activation. Targeting CCL2 and its receptors and TRPV1 receptors in combination with opioid therapy could significantly improve the analgesic properties of opioids, especially during pathological states.

scholarly journals Transient Receptor Potential Ankyrin 1 in Spinal Cord Dorsal Horn is Involved in Neuropathic Pain in Nerve Root Constriction Rats

2014 ◽  
Vol 10 ◽  
pp. 1744-8069-10-58 ◽  
Author(s):  
Tsuyoshi Miyakawa ◽  
Yoshinori Terashima ◽  
Tsuneo Takebayashi ◽  
Katsumasa Tanimoto ◽  
Takehito Iwase ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Dorsal Horn ◽  
Nerve Root ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Spinal Cord Dorsal Horn ◽  
Spinal Cord Dorsal ◽  
Transient Receptor
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