scholarly journals Chemokines and Pain in the Trigeminal System

2021 ◽  
Vol 2 ◽  
Author(s):  
Oscar O. Solis-Castro ◽  
Natalie Wong ◽  
Fiona M. Boissonade
Keyword(s):  
Cellular Localization ◽  
Large Family ◽  
Pain Modulation ◽  
Trigeminal System ◽  
Anatomical Location ◽  
Trigeminal Pain ◽  
Animal Pain ◽  
Pain Models ◽  
Central Nervous Systems ◽  
Primary Amino

Chemotactic cytokines or chemokines are a large family of secreted proteins able to induce chemotaxis. Chemokines are categorized according to their primary amino acid sequence, and in particular their cysteine residues that form disulphide bonds to maintain the structure: CC, CXC, CX3C, and XC, in which X represents variable amino acids. Among their many roles, chemokines are known to be key players in pain modulation in the peripheral and central nervous systems. Thus, they are promising candidates for novel therapeutics that could replace current, often ineffective treatments. The spinal and trigeminal systems are intrinsically different beyond their anatomical location, and it has been suggested that there are also differences in their sensory mechanisms. Hence, understanding the different mechanisms involved in pain modulation for each system could aid in developing appropriate pharmacological alternatives. Here, we aim to describe the current landscape of chemokines that have been studied specifically with regard to trigeminal pain. Searching PubMed and Google Scholar, we identified 30 reports describing chemokines in animal models of trigeminal pain, and 15 reports describing chemokines involved in human pain associated with the trigeminal system. This review highlights the chemokines studied to date at different levels of the trigeminal system, their cellular localization and, where available, their role in a variety of animal pain models.

Experimental evidence for weaker endogenous inhibition of trigeminal pain than extra-trigeminal pain in healthy individuals

Cephalalgia ◽  
2017 ◽  
Vol 38 (7) ◽  
pp. 1307-1315 ◽  
Author(s):  
Dan Levy ◽  
Lorin Abdian ◽  
Michal Dekel-Steinkeller ◽  
Ruth Defrin
Keyword(s):  
Pain Control ◽  
Pain Modulation ◽  
Primary Headaches ◽  
Healthy Individuals ◽  
Trigeminal Pain ◽  
Pain Syndromes ◽  
Body Regions ◽  
Endogenous Pain Modulation ◽  
High Prevalence ◽  
Pain Inhibition

Background and objectives The prevalence of pain syndromes that affect the territories innervated by the trigeminal nerve, such as headaches, is one of the highest and ranks second only to low back pain. A potential mechanism underlying this high prevalence may be a relatively weak endogenous pain modulation of trigeminal pain. Here, we sought to systematically compare endogenous pain modulation capabilities in the trigeminal region to those of extra-trigeminal regions in healthy subjects. Methods Healthy, pain free subjects (n = 17) underwent a battery of quantitative sensory testing to assess endogenous pain inhibition and pain enhancement efficiencies within and outside the trigeminal innervated region. Measurements included conditioned pain modulation (CPM), temporal summation of pain (TSP) and spatial summation of pain (SSP). Results Testing configurations that included trigeminal-innervated body regions displayed significantly weaker CPM when compared to extra-trigeminal innervated areas. SSP magnitude was smaller in the ophthalmic trigeminal innervation when compared to other body regions. TSP magnitude was not different between the different body regions tested. Conclusions Our findings point to regional differences in endogenous pain inhibition and suggest that in otherwise healthy individuals, the trigeminal innervation is subjected to a weaker inhibitory pain control than other body regions. Such weaker endogenous pain control could play, at least in part, a role in mediating the high prevalence of trigeminal-related pain syndromes, including primary headaches and TMD pain.

scholarly journals Analgesic Interaction Between Morphine with Fentanyl In Experimental Murine Pain

2021 ◽  
Author(s):  
Hugo F Miranda ◽  
Viviana Noriega ◽  
Fernando Sierralta ◽  
Ramon Sotomayor-Zarate ◽  
Juan Carlos Prieto
Keyword(s):  
Phase I ◽  
Dose Response ◽  
Multimodal Treatment ◽  
Binding Capacity ◽  
Tail Flick ◽  
Pharmacological Interaction ◽  
Isobolographic Analysis ◽  
Antinociceptive Action ◽  
Animal Pain ◽  
Pain Models

Abstract Opioids are among the most effective pain relievers available, however multimodal antinociception between opioids, has not been extensively studied in diverse animal pain models.In this study the pharmacological interaction of morphine with fentanyl was evaluated in different murine pain models by means of isobolographic analysis. In control animals, morphine and fentanyl produced a dose-related antinociceptive action in the murine assays and the rank of potency was: formalin hind paw phase I > formalin phase II > tail flick. Coadministration of morphine with fentanyl, in a fixed relation 1:1 of their ED50, produces a dose response in all tests and the isobologram resulted in synergism. Fentanyl was more effective than morphine which could be explained according the suggestion that opioids could be acting through other targets, with different binding capacity thru the regulation or activation of non-opioid receptors. Co-administration of morphine with fentanyl induces synergism in all murine trials, confirming the antinociceptive capacity of both opioids which would constitute a promisory idea to multimodal treatment of pain.

Antinociceptive properties of shikonin: in vitro and in vivo studies

2016 ◽  
Vol 94 (7) ◽  
pp. 788-796 ◽  
Author(s):  
Bhawana Gupta ◽  
Sabyasachi Chakraborty ◽  
Soumya Saha ◽  
Sunita Gulabsingh Chandel ◽  
Atul Kumar Baranwal ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Inhibitory Effect ◽  
Pain Modulation ◽  
In Vivo Studies ◽  
Channel Modulation ◽  
Pain Models ◽  
A Cell ◽  
Dose Dependent

Shikonin possess a diverse spectrum of pharmacological properties in multiple therapeutic areas. However, the nociceptive effect of shikonin is not largely known. To investigate the antinociceptive potential of shikonin, panel of GPCRs, ion channels, and enzymes involved in pain pathogenesis were studied. To evaluate the translation of shikonin efficacy in vivo, it was tested in 3 established rat pain models. Our study reveals that shikonin has significant inhibitory effect on pan sodium channel/N1E115 and NaV1.7 channel with half maximal inhibitory concentration (IC50) value of 7.6 μmol/L and 6.4 μmol/L, respectively, in a cell-based assay. Shikonin exerted significant dose dependent antinociceptive activity at doses of 0.08%, 0.05%, and 0.02% w/v in pinch pain model. In mechanical hyperalgesia model, dose of 10 and 3 mg/kg (intraperitoneal) produced dose-dependent analgesia and showed 67% and 35% reversal of hyperalgesia respectively at 0.5 h. Following oral administration, it showed 39% reversal at 30 mg/kg dose. When tested in first phase of formalin induced pain, shikonin at 10 mg/kg dose inhibited paw flinching by ∼71%. In all studied preclinical models, analgesic effect was similar or better than standard analgesic drugs. The present study unveils the mechanistic role of shikonin on pain modulation, predominantly via sodium channel modulation, suggesting that shikonin could be developed as a potential pain blocker.

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.

Animal pain models

2004 ◽  
Vol 5 (3) ◽  
pp. S17
Author(s):  
V. Smith ◽  
C. Beyer ◽  
M. Brandt
Keyword(s):  
Animal Pain ◽  
Pain Models

Animal pain models

2004 ◽  
Vol 5 (3) ◽  
pp. S17
Author(s):  
P. Robinson ◽  
K. Smith ◽  
A. Loescher ◽  
F. Boissonade ◽  
S. Atkins ◽  
...  
Keyword(s):  
Animal Pain ◽  
Pain Models

230 TAPENTADOL: EFFICACY PROFILE OF A NOVEL CENTRALLY ACTIVE ANALGESIC WITH A DUAL MODE OF ACTION IN ANIMAL PAIN MODELS

2006 ◽  
Vol 10 (S1) ◽  
pp. S62c-S62 ◽  
Author(s):  
J. Vry ◽  
T.M. Tzschentke ◽  
T. Christoph ◽  
M. Méen ◽  
B. Kögel ◽  
...  
Keyword(s):  
Mode Of Action ◽  
Dual Mode ◽  
Animal Pain ◽  
Pain Models ◽  
Efficacy Profile

scholarly journals Modulating Innate and Adaptive Immunity by (R)-Roscovitine: Potential Therapeutic Opportunity in Cystic Fibrosis

2016 ◽  
Vol 8 (4) ◽  
pp. 330-349 ◽  
Author(s):  
Laurent Meijer ◽  
Deborah J. Nelson ◽  
Vladimir Riazanski ◽  
Aida G. Gabdoulkhakova ◽  
Geneviève Hery-Arnaud ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Therapeutic Agent ◽  
Drug Candidate ◽  
Innate And Adaptive Immunity ◽  
Animal Pain ◽  
Pain Models ◽  
Therapeutic Opportunity ◽  
Induction Of Apoptosis ◽  
Preclinical Safety ◽  
Phase I And Ii

(R)-Roscovitine, a pharmacological inhibitor of kinases, is currently in phase II clinical trial as a drug candidate for the treatment of cancers, Cushing's disease and rheumatoid arthritis. We here review the data that support the investigation of (R)-roscovitine as a potential therapeutic agent for the treatment of cystic fibrosis (CF). (R)-Roscovitine displays four independent properties that may favorably combine against CF: (1) it partially protects F508del-CFTR from proteolytic degradation and favors its trafficking to the plasma membrane; (2) by increasing membrane targeting of the TRPC6 ion channel, it rescues acidification in phagolysosomes of CF alveolar macrophages (which show abnormally high pH) and consequently restores their bactericidal activity; (3) its effects on neutrophils (induction of apoptosis), eosinophils (inhibition of degranulation/induction of apoptosis) and lymphocytes (modification of the Th17/Treg balance in favor of the differentiation of anti-inflammatory lymphocytes and reduced production of various interleukins, notably IL-17A) contribute to the resolution of inflammation and restoration of innate immunity, and (4) roscovitine displays analgesic properties in animal pain models. The fact that (R)-roscovitine has undergone extensive preclinical safety/pharmacology studies, and phase I and II clinical trials in cancer patients, encourages its repurposing as a CF drug candidate.

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