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Francisco Pellicer,1 Juan M Ortega-Legaspi,2 Rodrigo Martín,3 Sergio Solís-Nájera,4 Lucía Magis-Weinberg,5 Martha León-Olea,6 Ariel Graff-Guerrero,7,8 Camilo de la Fuente-Sandoval,9 Alfredo O Rodriguez3 1Laboratorio de Neurofisiología Integrativa, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, CDMX, México; 2Department of Medicine, Division of Cardiovascular Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; 3Departamento de Ingeniería Eléctrica, Universidad Autónoma Metropolitana Iztapalapa, CDMX, México; 4Departamento de Física, Facultad de Ciencias, Universidad Nacional Autónoma de México, CDMX, México; 5Department of Psychology, University of Washington Guthrie Hall (GTH), Seattle, WA, USA; 6Departamento de Neuromorfología Funcional, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, CDMX, México; 7Brain Health Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada; 8Department of Psychiatry, University of Toronto, Toronto, ON, Canada; 9Laboratorio de Psiquiatría Experimental, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, CDMX, MéxicoCorrespondence: Francisco Pellicer, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Calzada México Xochimilco 101, San Lorenzo Huipulco, Alcaldía Tlalpan, CDMX, 14370, México, Tel +52 55 41605063, Email pellicer@imp.edu.mxObjective: Pain constitutes an essential alarm for preserving the organism’s integrity. Damage to the nervous system produces a pathological condition known as neuropathic pain.Purpose: Blood oxygenation level-dependent (BOLD) and functional magnetic resonance imaging (fMRI) have been widely used to map neuroanatomy and the active regions of interest (ROI) of nociceptive processing. Our study explored the brain’s BOLD response in rats after thermal noxious stimulation, immediately after sciatic nerve damage and during 75 minutes after surgical lesion of the sciatic nerve.Methods: Nine male Wistar rats were tested; the experiments were performed on a 7-Tesla /21-cm Varian Agilent system. This approach allowed, for the first time, to measure in vivo the BOLD changes in brain regions involved with the pain process: cingulated (ACC), somatosensory (S1), and insular cortices (IC), as well as thalamus (Th) and ventral tegmental area (VTA) related with acute thermal pain and during the early stages of sciatic denervation that produce neuropathic pain.Results: During thermonociception scan, all subjects showed BOLD activation in the ROIs determined as ACC, S1, Th, IC and VTA. After denervation, these regions continued to show activation with a slow decrement in intensity for the duration of the experiment. The results suggest that these brain structures are overactive during the genesis of neuropathic pain.Conclusion: The study shows for the first time continuous activation of the pain matrix following an acute thermal nociceptive stimulus followed by neuropathic damage. These results have given insight into the early stages of the development of neuropathic pain in vivo.Keywords: fMRI, resting state, neuropathic pain, pain matrix, chronic pain, acute pain

Ulises Coffeen, Francisco Pellicer Research in Neurosciences, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Mexico City, México 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 κ 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

El objetivo del presente trabajo fue describir y analizar la situación en España de los productos de venta ilícita, tanto medicamentos como complementos alimenticios, poniendo en conocimiento las principales acciones realizadas en los últimos meses y su contextualización a nivel mundial. Asimismo, servir de alerta sobre la magnitud del problema y la importancia del papel del farmacéutico comunitario. Se realizó una búsqueda de información tanto a nivel nacional como internacional y se realizó un análisis descriptivo de las Notas Informativas de la Agencia Española de Medicamentos y Productos Sanitarios (AEMPS) (medicamentos ilegales, uso humano, 2015). Los productos de venta ilícita representan un problema grave para la salud pública que no ha parado de aumentar. En España, en 2015 se publicaron 20 notas donde se prohibió y retiró un total de 35 productos. Dichos productos estaban comercializados como complemento alimenticio y presentaban un principio activo en cantidad suficiente para conferirle legalmente la condición de medicamento. El 86% se dirigía a la disfunción eréctil. Para minimizar este problema, es imprescindible la colaboración internacional, siendo la última y más importante operación PANGEA VIII, en junio del 2015, implicando a 115 países. En enero del 2016 entró en vigor la Convención Medicrime, tratado internacional sobre la falsificación de productos médicos y delitos similares. Por otro lado, también es necesario concienciar a la ciudadanía y dotarla de mecanismos para identificar el riesgo potencial. Los productos adquiridos fuera de los canales legales de distribución no aseguran el cumplimiento de las normas de correcta fabricación, distribución, ni posterior conservación y carecen de la información adecuada.

Objective: To assess the effect of a 2-week treatment with dexibuprofen, in comparison with ibuprofen and diclofenac, on pepsinogen plasma concentrations and gastrointestinal mucosa, as well as the correlation of these changes with gastrointestinal mucosal injury. Methods: 60 patients with rheumatologic disease in chronic therapy with NSAID, were included. After a 7-day rtm-in period patients were randomly assigned to receive a 14-day treatment with dexibuprofen (Group A; Day 1–3 = 400 mg t.i.d; Day 4–14 = 400 mg b.i.d.), ibuprofen (Group B; Day 1–3 = 800 mg t.i.d; Day 4–14 = 800 mg b.i.d.) or diclofenac (Group C; Day 1–3 = 50 mg t.i.d; Day 4–14 = 50 mg b.i.d.). Upper gastrointestinal endoscopy (Day 15), capsule-endoscopy (Day 16, 7 patients of each group) and determination of pepsinogen plasma concentrations were performed (basal and Day 15). A semiquantitative scale was designed for the assessment of the gastrointestinal mucosa. Results: No differences in plasma pepsinogen were found between treatment groups or gastrointestinal injury grades or between basal and post-therapy determinations. Dexibuprofen showed gastroduodenal and mucosal injury in fewer patients (42.1%) than was the case with ibuprofen (5%; p = 0.003) and diclofenac (30%; p = N.S.). Dexibuprofen administration was also associated with more patients having no intestinal mucosal damage (42.86% vs. 28.7% in the diclofenac group and 14.29% in the ibuprofen group; p = 0.0175). The rate of clinical adverse events was similar in Groups A, B and C (28%, 38% and 34%). Conclusions: Dexibuprofen showed a lower rate of gastroduodenal and intestinal mucosal injury. This effect was not mediated by modifications of plasma pepsinogen levels. [ABSTRACT FROM AUTHOR]

The role of nitric oxide as a neurotransmitter in the olfactory and chemoreception systems of invertebrates has been well documented. This suggests an early and efficient sensory detection system that is evolutionarily preserved in various species, including vertebrates and invertebrates. Additionally, the presence of a nitric oxide neurotransmitter system has been reported in molluscs, particularly in octopus species. In this work, we present evidence for the existence of nitric oxide synthase in neurons and fibers, as well as its anatomical localization in various nuclei involved in chemosensory integration and the motor responses associated with these processes in Octopus maya., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Pain is a morbidity or comorbidity with a high incidence that significantly impacts the well-being of patients. In this study, we evaluated the effects of systemic administration of tramadol, a weak mu-opioid receptor (MOR) agonist, plus quinpirole (a D2-like receptor agonist). The study was performed in naïve rats and in rats with induced inflammatory and neuropathic pain. To measure the antinociceptive effect of the drugs, thermonociceptive and mechanonociceptive stimuli were applied and the emotional aspects of pain were evaluated using conditional place preference (CPP) experiments. Systemic quinpirole produced an antinociceptive effect only in naïve male rats. In naïve female animals, a small but significant pronociceptive effect was observed following quinpirole application. Tramadol plus quinpirole in male animals reversed allodynia and hyperalgesia induced by inflammatory and neuropathic insults, which were not alleviated by either drug alone. CPP experiments revealed that systemic quinpirole plus tramadol treatment was effective only in an inflammatory pain model. To evaluate whether tolerance to the antinociceptive effect was prevented by the combination of the drugs, a repeated administration five-day trial of tramadol plus quinpirole was evaluated under inflammatory pain conditions; quinpirole only slightly prevented the antinociceptive tolerance of MOR agonists. D2-like agonists are effective adjuvants for treating painful conditions in combination with a low dose of MOR agonists. Our results could lead to an investigation of whether these dopaminergic drugs in combination with opioids might reduce the MOR agonist dose while obtaining a higher analgesic effect with fewer side effects in humans., (© 2024 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

The insular cortex (IC) is a brain region that both receives relevant sensory information and is responsible for emotional and cognitive processes, allowing the perception of sensory information. The IC has connections with multiple sites of the pain matrix, including cortico-cortical interactions with the anterior cingulate cortex (ACC) and top-down connections with sites of descending pain inhibition. We explored the changes in the extracellular release of serotonin (5HT) and its major metabolite, 5-hydroxyindoleacetic acid (5HIAA), after inflammation was induced by carrageenan injection. Additionally, we explored the role of 5HT receptors (the 5HT1A, 5HT2A, and 5HT3 receptors) in the IC after inflammatory insult. The results showed an increase in the extracellular levels of 5HT and 5-HIAA during the inflammatory process compared to physiological levels. Additionally, the 5HT1A receptor was overexpressed. Finally, the 5HT1A, 5HT2A, and 5HT3 receptor blockade in the IC had antinociceptive effects. Our results highlight the role of serotonergic neurotransmission in long-lasting inflammatory nociception within the IC.