The role of endocannabinoids in pain modulation

2013 ◽  
Vol 27 (1) ◽  
pp. 64-80 ◽  
Author(s):  
Panagiotis Zogopoulos ◽  
Ioanna Vasileiou ◽  
Efstratios Patsouris ◽  
Stamatios E. Theocharis
Keyword(s):  
Pain Modulation

scholarly journals Characterization of New TRPM8 Modulators in Pain Perception

2019 ◽  
Vol 20 (22) ◽  
pp. 5544 ◽  
Author(s):  
Carmen De Caro ◽  
Claudia Cristiano ◽  
Carmen Avagliano ◽  
Alessia Bertamino ◽  
Carmine Ostacolo ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Pain Perception ◽  
Transient Receptor Potential ◽  
Pain Modulation ◽  
The Body ◽  
Sprague Dawley ◽  
Transient Receptor Potential Melastatin ◽  
Pain Models ◽  
Excessive Activation

Background: Transient Receptor Potential Melastatin-8 (TRPM8) is a non-selective cation channel activated by cold temperature and by cooling agents. Several studies have proved that this channel is involved in pain perception. Although some studies indicate that TRPM8 inhibition is necessary to reduce acute and chronic pain, it is also reported that TRPM8 activation produces analgesia. These conflicting results could be explained by extracellular Ca2+-dependent desensitization that is induced by an excessive activation. Likely, this effect is due to phosphatidylinositol 4,5-bisphosphate (PIP2) depletion that leads to modification of TRPM8 channel activity, shifting voltage dependence towards more positive potentials. This phenomenon needs further evaluation and confirmation that would allow us to understand better the role of this channel and to develop new therapeutic strategies for controlling pain. Experimental approach: To understand the role of TRPM8 in pain perception, we tested two specific TRPM8-modulating compounds, an antagonist (IGM-18) and an agonist (IGM-5), in either acute or chronic animal pain models using male Sprague-Dawley rats or CD1 mice, after systemic or topical routes of administration. Results: IGM-18 and IGM-5 were fully characterized in vivo. The wet-dog shake test and the body temperature measurements highlighted the antagonist activity of IGM-18 on TRPM8 channels. Moreover, IGM-18 exerted an analgesic effect on formalin-induced orofacial pain and chronic constriction injury-induced neuropathic pain, demonstrating the involvement of TRPM8 channels in these two pain models. Finally, the results were consistent with TRPM8 downregulation by agonist IGM-5, due to its excessive activation. Conclusions: TRPM8 channels are strongly involved in pain modulation, and their selective antagonist is able to reduce both acute and chronic pain.

scholarly journals The Role of Corticotropin-Releasing Hormone at Peripheral Nociceptors: Implications for Pain Modulation

Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 623
Author(s):  
Haiyan Zheng ◽  
Ji Yeon Lim ◽  
Jae Young Seong ◽  
Sun Wook Hwang
Keyword(s):  
Signal Transmission ◽  
Brain Regions ◽  
Pain Modulation ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Inhibitory Function ◽  
Peripheral Pain ◽  
Functional Profiles ◽  
Pituitary Adrenal Axis

Peripheral nociceptors and their synaptic partners utilize neuropeptides for signal transmission. Such communication tunes the excitatory and inhibitory function of nociceptor-based circuits, eventually contributing to pain modulation. Corticotropin-releasing hormone (CRH) is the initiator hormone for the conventional hypothalamic-pituitary-adrenal axis, preparing our body for stress insults. Although knowledge of the expression and functional profiles of CRH and its receptors and the outcomes of their interactions has been actively accumulating for many brain regions, those for nociceptors are still under gradual investigation. Currently, based on the evidence of their expressions in nociceptors and their neighboring components, several hypotheses for possible pain modulations are emerging. Here we overview the historical attention to CRH and its receptors on the peripheral nociception and the recent increases in information regarding their roles in tuning pain signals. We also briefly contemplate the possibility that the stress-response paradigm can be locally intrapolated into intercellular communication that is driven by nociceptor neurons. Such endeavors may contribute to a more precise view of local peptidergic mechanisms of peripheral pain modulation.

A psychophysical study of endogenous analgesia: The role of the conditioning pain in the induction and magnitude of conditioned pain modulation

2011 ◽  
Vol 15 (5) ◽  
pp. 491-497 ◽  
Author(s):  
Rony-Reuven Nirl ◽  
Yelena Granovskyl ◽  
David Yarnitskyl ◽  
Elliot Sprecherl ◽  
Michal Granotl
Keyword(s):  
Pain Modulation ◽  
Conditioned Pain Modulation ◽  
Endogenous Analgesia ◽  
Psychophysical Study

scholarly journals Microglia: a newly discovered role in visceral hypersensitivity?

2006 ◽  
Vol 2 (4) ◽  
pp. 271-277 ◽  
Author(s):  
Carl Y. Saab ◽  
Jing Wang ◽  
Chunping Gu ◽  
Kirsten N. Garner ◽  
Elie D. Al-Chaer
Keyword(s):  
Visceral Pain ◽  
Thermal Hyperalgesia ◽  
Radiant Heat ◽  
Pain Modulation ◽  
Visceral Hypersensitivity ◽  
Visceral Sensitivity ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Before And After

AbstractGiven the growing body of evidence for a role of glia in pain modulation, it is plausible that the exaggerated visceral pain in chronic conditions might be regulated by glial activation. In this study, we have investigated a possible role for microglia in rats with chronic visceral hypersensitivity and previously documented altered neuronal function. Experiments were performed on adult male Sprague-Dawley rats pre-treated with neonatal colon irritation (CI) and on control rats. Effects of fractalkine (FKN, a chemokine involved in neuron-to-microglia signaling) and of minocycline (an inhibitor of microglia) on visceral sensitivity were examined. Visceral sensitivity was assessed by recording the electromyographic (EMG) responses to graded colorectal distension (CRD) in mildly sedated rats. Responses to CRD were recorded before and after injection of FKN, minocycline or vehicle. Somatic thermal hyperalgesia was measured by latency of paw withdrawal to radiant heat. The pattern and intensity of microglial distribution at L6–S2 in the spinal cord was also compared in rats with CI and controls by fluorescence microscopy using OX-42. Results show that: (1) FKN significantly facilitated EMG responses to noxious CRD by >52% in control rats. FKN also induced thermal hyperalgesia in control rats, consistent with previous reports; (2) minocycline significantly inhibited EMG responses to noxious CRD by >70% in rats with CI compared to controls 60 min after injection. The anti-nociceptive effect of minocycline lasted for 180 min in rats with CI, reaching peak values 60 min after injection. Our results show that FKN enhances visceral and somatic nociception, whereas minocycline inhibits visceral hypersensitivity in chronically sensitized rats, which indicates a role for microglia in visceral hypersensitivity.

scholarly journals N/OFQ modulates orofacial pain induced by tooth movement through CGRP-dependent pathways

2020 ◽  
Author(s):  
Xinyu Yan ◽  
Han Han ◽  
Shizhen Zhang ◽  
Yanzhu Lu ◽  
Linghuan Ren ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Tooth Movement ◽  
Orofacial Pain ◽  
Pain Modulation ◽  
Trigeminal Ganglia ◽  
Orphanin Fq ◽  
Pain Model ◽  
Calcitonin Gene ◽  
Agonist And Antagonist

Abstract Background: Nociceptin/orphanin FQ (N/OFQ) has been revealed to play bidirectional roles in orofacial pain modulation. Calcitonin gene-related peptide (CGRP) is a well-known pro-nociceptive molecule that participates in the modulation of orofacial pain. We aimed to determine the effects of N/OFQ on the modulation of orofacial pain and on the release of CGRP.Methods: Orofacial pain model was established by ligating springs between incisors and molars in rats for the simulation of tooth movement. The expression level of N/OFQ was determined and pain level scored in response to orofacial pain. Both agonist and antagonist of N/OFQ receptor were administered to examine their effects on pain and the expression of CGRP in trigeminal ganglia (TG). Moreover, gene therapy based on the overexpression of N/OFQ was delivered to validate the modulatory role of N/OFQ on pain and CGRP expression.Results: Tooth movement elicited orofacial pain and an elevation in N/OFQ expression. N/OFQ exacerbated orofacial pain and upregulated CGRP expression in TG, while UFP-101 alleviated pain and downregulated CGRP expression. N/OFQ-based gene therapy was successful in overexpressing N/OFQ in TG, which resulted in pain exacerbation and elevation of CGRP expression in TG.Conclusions: N/OFQ exacerbated orofacial pain possibly through upregulating CGRP.

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