Expression of the dopaminergic D1 and D2 receptors in the anterior cingulate cortex in a model of neuropathic pain

<p>Abstract</p> <p>Background</p> <p>The anterior cingulate cortex (ACC) has been related to the affective component of pain. Dopaminergic mesocortical circuits, including the ACC, are able to inhibit neuropathic nociception measured as autotomy behaviour. We determined the changes in dopamine D1 and D2 (D1R and D2R) receptor expression in the ACC (cg1 and cg2) in an animal model of neuropathic pain. The neuropathic group had noxious heat applied in the right hind paw followed 30 min. later by right sciatic denervation. Autotomy score (AS) was recorded for eight days and subsequently classified in low, medium and high AS groups. The control consisted of naïve animals.</p> <p>A semiquantitative RT-PCR procedure was done to determine mRNA levels for D1R and D2R in cg1 and cg2, and protein levels were measured by Western Blot.</p> <p>Results</p> <p>The results of D1R mRNA in cg1 showed a decrease in all groups. D2R mRNA levels in cg1 decreased in low AS and increased in medium and high AS. Regarding D1R in cg2, there was an increase in all groups. D2R expression levels in cg2 decreased in all groups. In cg1, the D2R mRNA correlated positively with autotomy behaviour. Protein levels of D2R in cg1 increased in all groups but to a higher degree in low AS. In cg2 D2R protein only decreased discretely. D1R protein was not found in either ACC region.</p> <p>Conclusions</p> <p>This is the first evidence of an increase of inhibitory dopaminergic receptor (D2R) mRNA and protein in cg1 in correlation with nociceptive behaviour in a neuropathic model of pain in the rat.</p

Salvia divinorum: from recreational hallucinogenic use to analgesic and anti-inflammatory action

Ulises Coffeen, Francisco Pellicer Research in Neurosciences, Instituto Nacional de Psiquiatr&iacute;a Ram&oacute;n de la Fuente Mu&ntilde;iz, Mexico City, M&eacute;xico Abstract: Salvia divinorum is a herbal plant native to the southwest region of Mexico. Traditional preparations of this plant have been used in illness treatments that converge with inflammatory conditions and pain. Currently, S. divinorum extracts have become popular in several countries as a recreational drug due to its hallucinogenic effects. Its main active component is a diterpene named salvinorin A (SA), a potent naturally occurring hallucinogen with a great affinity to the &kappa; opioid receptors and with allosteric modulation of cannabinoid type 1 receptors. Recent biochemical research has revealed the mechanism of action of the anti-inflammatory and analgesic effect of SA at the cellular and molecular level. Nevertheless, because of their short-lasting and hallucinogenic effect, the research has focused on discovering a new analogue of SA that is able to induce analgesia and reduce inflammation with a long-lasting effect but without the hallucinatory component. In this review, we explore the role of S. divinorum, SA and its analogues. We focus mainly on their analgesic and anti-inflammatory roles but also mention their psychoactive properties. Keywords: Salvia divinorum, salvinorin A, pain, inflammation, psychoactivity &nbsp

TRH injected into the nucleus accumbens shell releases dopamine and reduces feeding motivation in rats

The thyrotropin-releasing hormone (TRH), an anorexigenic factor that reduces food intake in food-restricted animals, may be involved in motivation for food. Injected centrally, TRH impairs acquisition of food-rewarded behavior. Through the TRH-R1 receptors, TRH injected in the nucleus accumbens increases dopamine content—perhaps the mechanism by which the peptide modulates food motivation. This, however, is still to be demonstrated. We sought to evaluate dopamine release by microdialysis after a TRH injection into the nucleus accumbens shell in free-moving fasted rats. In addition, we assessed dopamine content and turnover by HPLC and the relationship with the motivation for food by analyzing the performance of rats during a progressive-ratio (PR) operant-conditioning test. Finally, we determined serum leptin and triiodothyronine (T3) levels in order to evaluate the animals’ metabolic response to food restriction and the impact of intra-accumbal TRH administration on circulating hormones. Intra-accumbal injections of TRH reduced food intake in food-restricted rats—compared to counterparts treated with saline—, without further decreasing T3 or leptin levels, which dropped due to their dietary regime. TRH-injected rats had lower breaking points on the PR schedule, which indicated lower motivation to eat. Accordingly, compared to saline-treated animals, dopamine release and turnover increased in the nucleus accumbens of TRH-injected rats, a finding that suggests a relationship between motivation for food and TRH-induced release of dopamine

Chemotherapy-induced neuropathic pain characteristics in Mexico&rsquo;s National Cancer Center pain clinic

Ulises Coffeen,1 Marco Antonio Sotomayor-Sobrino,2,3 Ariadna Jim&eacute;nez-Gonz&aacute;lez,2,3 Luis Gerardo Balcazar-Ochoa,3 Pamela Hern&aacute;ndez-Delgado,3 Ana Fres&aacute;n,1 Ricardo Plancarte-Sanchez,4 Samantha Daniela Arias-Mu&ntilde;&oacute;z,5 Abraham Ochoa-Aguilar2,61Laboratorio de Neurofisiolog&iacute;a Integrativa. Investigaciones en Neurociencias y Divisi&oacute;n de Investigaci&oacute;n Cl&iacute;nica, Instituto Nacional de Psiquiatr&iacute;a Ram&oacute;n de la Fuente Mu&ntilde;iz, Clinical Research Division, Mexico City, Mexico; 2Hospital Loma Linda, Translational Research Laboratory, Naucalpan, Mexico; 3Universidad Nacional Aut&oacute;noma de M&eacute;xico, Faculty of Medicine, Mexico City, Mexico; 4Instituto Nacional de Cancerolog&iacute;a, Cl&iacute;nica de dolor, Tlalpan, Mexico; 5Universidad Anahuac Norte, Faculty of Medicine, Huixquilucan Mexico, Huixquilucan, Mexico; 6Universidad La Salle, Mexican Faculty of Medicine, Mexico City, MexicoIntroduction: Chemotherapy (CT) is one of the most commonly used pharmacological approaches in cancer treatment. However, CT induces damage to several tissues causing significant deleterious effects in cancer survivors being chemotherapy-induced neuropathic pain (CINP) among the most commonly reported. CINP is thought to be present in up to 68.1% of the patients within 1 month of receiving CT. Due to the fact that reliable statistic information is scarce in several Latin American countries&rsquo; diagnosis and treatment of this side-effect may be delayed directly affecting patients. Therefore, the aim of the present study was to determine and present the incidence and features of CINP in patients with cancer attending the Pain Management Clinic at Mexicos&rsquo; National Institute of Cancerology in Mexico City.Methods: We performed a retrospective, file-based analysis of all the patients treated in the Pain Management Clinic at the National Institute at Cancer in Mexico from January 2016 to January 2017.Results: CINP was found in 30.9% of the patients. The basal VAS was on average 2.5 upon arrival to the Pain Management Unit and 2.4 at the end of treatment (p&gt;0.05). The patients with the highest risk of developing CINP were those treated with paclitaxel Odds ratio 8.3 (p&lt;0.01), followed by platins OR 4 (p&lt;0.01), vincristine OR 1.5 (p=0.01) and thalidomide OR 1.1 (p=0.01).Conclusion: Incidence of CINP was similar to previous reports; however, the number of variables related to this type of pain in our cohort may open a new line of research and highlight the importance of this particular issue to our health system. It is necessary to develop a mechanism to predict the risk of patients to suffer CINP and to search the mechanism to control and reduce the suffering related to the current treatments.Keywords: Pain, chemotherapy, neuropathy, paclitaxe

Ceftriaxone and clavulanic acid induce antiallodynia and anti-inflammatory effects in rats using the carrageenan model

Abraham Ochoa-Aguilar,1,2 Rosa Ventura-Martinez,1 Marco Antonio Sotomayor-Sobrino,1 Ruth Jaimez,1 Ulises Coffeen,3 Ariadna Jim&eacute;nez-Gonz&aacute;lez,2 Luis Gerardo Balc&aacute;zar-Ochoa,1 Rafael P&eacute;rez-Medina-Carballo,2 Rodolfo Rodriguez,1 Ricardo Plancarte-S&aacute;nchez4 1Pharmacology Department, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, M&eacute;xico; 2Research Department, Mexican Faculty of Medicine, La Salle University, Mexico City, M&eacute;xico; 3Instituto Nacional de Psiquiatr&iacute;a Ram&oacute;n de la Fuente Mu&ntilde;iz, Mexico City, M&eacute;xico; 4Pain Clinic, National Cancer Institute of Mexico, Mexico City, M&eacute;xico Introduction: Ceftriaxone (CFX) and clavulanic acid (CA) are 2 &beta;-lactam molecules widely used as antibiotics. However, several reports of their antiallodynic properties have been published in recent years. Although this effect has been considered mostly due to a GLT1 overexpression, these molecules have also been proven to induce direct immunomodulation. In this work, we determine the acute analgesic effect of CFX and CA in an inflammatory pain model and assess if their administration may induce anti-inflammatory effects. Methods: The carrageenan (Carr) test was used as an inflammatory pain model. Both mechanical and thermal responses were analyzed after CFX and CA administration at different times. A plethysmometer was used to determine inflammation. Also, TNF-&alpha; and IL-10 serum concentrations were determined by enzyme-linked immunosorbent assay. Results: Both CFX and CA induced a significant thermal antiallodynic effect 3 and 24 h after administration. Furthermore, CA induced a mechanical antiallodynic effect 30, 60, and 90 min after administration. Moreover, a significant anti-inflammatory effect was found for both molecules 24 h after Carr injection. Also, both CA and CFX modulated TNF-&alpha; and IL-10 serum concentrations at different times. Conclusion: Our results provide evidence that both CFX and CA cause an analgesic effect on a Carr inflammatory pain model and that said analgesic effect differs between each &beta;-lactam molecule. Furthermore, this effect may be related to an anti-inflammatory effect of both molecules and a direct TNF-&alpha; and IL-10 serum concentration modulation. Keywords: ceftriaxone, clavulanic acid, inflammatory pain, TNF-&alpha; concentration, &beta;-lactam molecules, analgesic effect, antiallodynic propertie