Opioid analgesics for nociceptive cancer pain: A comprehensive review.

Pain is one of the most burdensome symptoms in people with cancer, and opioid analgesics are considered the mainstay of cancer pain management. For this review, the authors evaluated the efficacy and toxicities of opioid analgesics compared with placebo, other opioids, nonopioid analgesics, and nonpharmacologic treatments for background cancer pain (continuous and relatively constant pain present at rest), and breakthrough cancer pain (transient exacerbation of pain despite stable and adequately controlled background pain). They found a paucity of placebo-controlled trials for background cancer pain, although tapentadol or codeine may be more efficacious than placebo (moderate-certainty to low-certainty evidence). Nonsteroidal anti-inflammatory drugs including aspirin, piroxicam, diclofenac, ketorolac, and the antidepressant medicine imipramine, may be at least as efficacious as opioids for moderate-to-severe background cancer pain. For breakthrough cancer pain, oral transmucosal, buccal, sublingual, or intranasal fentanyl preparations were identified as more efficacious than placebo but were more commonly associated with toxicities, including constipation and nausea. Despite being recommended worldwide for the treatment of cancer pain, morphine was generally not superior to other opioids, nor did it have a more favorable toxicity profile. The interpretation of study results, however, was complicated by the heterogeneity in the study populations evaluated. Given the limited quality and quantity of research, there is a need to reappraise the clinical utility of opioids in people with cancer pain, particularly those who are not at the end of life, and to further explore the effects of opioids on immune system function and quality of life in these individuals.

Protein Kinase A Inhibitor Attenuates the Antinociceptive Effect of NMDA-Receptor Channel Antagonists in the Capsaicin Test in Mice.

Acute nociceptive pain in mice caused by subcutaneous (intraplantar) injection of TRPV1 ion channel agonist capsaicin (1.6 µg/mouse) and the effects of protein kinase A inhibitor H-89 (0.05 mg/mouse, intraplantar injection) and NMDA receptor channel antagonists MK-801 (7.5 and 15 µg/mouse, topical application) and hemantane (0.5 mg/mouse, topical application) on the pain were assessed. MK-801 and hemantane were found to reduce the duration of the pain response. H-89 did not significantly affect the pain in animals, but preliminary administration of this drug abolished the antinociceptive effect of MK-801 (7.5 µg/mouse) and weakens the effect of hemantane (0.5 mg/mouse).

Effects of Euphorbia characias subsp. characias flower extracts on nociceptive pain and acute inflammatory models in mice.

Pain and inflammation are major health issues worldwide, leading to negative consequences. Despite several drugs being available to manage these conditions, their effectiveness can be limited by cost, adverse reactions, and potential tolerance and dependence with long-term use. Euphorbia characias traditionally used in folk medicine for its diverse biological activities - including antiproliferative, antimicrobial, and anti-inflammatory effects - has not been extensively studied in vivo for its analgesic and anti-inflammatory properties. In this study, the antinociceptive and anti-inflammatory properties of the water and ethanolic extracts of E. characias flowers (ECAEFl and ECEEFl) were evaluated using various models. Both extracts significantly reduced paw licking time in a formalin-induced paw licking model, with ECAEFl specifically targeting and ECEEFl affecting both the neurogenic and inflammatory phases. Additionally, in the carrageenan-induced cell migration model, both extracts showed a significant decrease in leukocyte migration, protein extravasation and nitric oxide levels, further demostrating their anti-inflammatory activity. High-Resolution HPLC-ESI-QTOF-MS-MS and HPLC-PDA analysis characterized the chemical composition of the extracts, identifying a significant presence of phenolic compounds, particularly quercetin and its derivatives, which likely contribute to the observed biological activities. These findings highlight the potential of E. characias extracts as natural sources of compounds with antinociceptive and anti-inflammatory properties. Further investigations are needed to elucidate the underlying mechanisms and explore their therapeutic potential in pain and inflammation-related disorders.

The superoxide anion donor, potassium superoxide, induces pain and inflammation in mice through production of reactive oxygen species and cyclooxygenase-2

It is currently accepted that superoxide anion (O2•−) is an important mediator in pain and inflammation. The role of superoxide anion in pain and inflammation has been mainly determined indirectly by modulating its production and inactivation. Direct evidence using potassium superoxide (KO2), a superoxide anion donor, demonstrated that it induced thermal hyperalgesia, as assessed by the Hargreaves method. However, it remains to be determined whether KO2 is capable of inducing other inflammatory and nociceptive responses attributed to superoxide anion. Therefore, in the present study, we investigated the nociceptive and inflammatory effects of KO2. The KO2-induced inflammatory responses evaluated in mice were: mechanical hyperalgesia (electronic version of von Frey filaments), thermal hyperalgesia (hot plate), edema (caliper rule), myeloperoxidase activity (colorimetric assay), overt pain-like behaviors (flinches, time spent licking and writhing score), leukocyte recruitment, oxidative stress, and cyclooxygenase-2 mRNA expression (quantitative PCR). Administration of KO2 induced mechanical hyperalgesia, thermal hyperalgesia, paw edema, leukocyte recruitment, the writhing response, paw flinching, and paw licking in a dose-dependent manner. KO2 also induced time-dependent cyclooxygenase-2 mRNA expression in the paw skin. The nociceptive, inflammatory, and oxidative stress components of KO2-induced responses were responsive to morphine (analgesic opioid), quercetin (antioxidant flavonoid), and/or celecoxib (anti-inflammatory cyclooxygenase-2 inhibitor) treatment. In conclusion, the well-established superoxide anion donor KO2 is a valuable tool for studying the mechanisms and pharmacological susceptibilities of superoxide anion-triggered nociceptive and inflammatory responses ranging from mechanical and thermal hyperalgesia to overt pain-like behaviors, edema, and leukocyte recruitment.

Buprenorfina transdérmica en el manejo del dolor crónico nociceptivo y neuropático no oncológico en ortopedia / Buprenorfine transdermal matrix patch in the treatment of chronic nociceptive non malignant pain and neurophatic pain in the orthopaedic patology

Objetivo: siendo el año del dolor musculoesquelético, es importante evitar el subtratamiento, dado la prevalencia de dolor crónico, los costos, limitación funcional y disminución de la calidad de vida en el paciente ortopédico, requiriéndose de vías menos invasivas, como la administración transdérmica, a través de sistema matricial de buprenorfina, en base a su liposolubilidad, y biodisponibilidad, sin riesgo de hiperalgesia ni afectación del sistema inmune, considerando su efecto techo en depresión respiratoria, y su empleo en comorbilidad renal y hepática. Material y métodos: estudio longitudinal, prospectivo, aleatorizado, de septiembre de 2008 a febrero de 2010, en el servicio de algología de orthocaz, unidad de ortopedia. N=108 de ambos sexos bajo consentimiento informado. Resultados: prevalencia de dolor en consulta externa de ortopedia r= 60-80 por ciento, x = 70, el crónico nociceptivo mayor de 30 por ciento y neuropático 1, 5 por ciento con predominio en el sexo femenino de 53,8 por ciento y, etiológicamente, el síndrome de columna fallida ocupa 40,7 por ciento, osteoartrosis 44, 4 por ciento, edad X= 66,59 años r= 20-85, dolor neuropático crónico secundario a metástasis en columna lumbar 3,7. La causa más común fue cáncer prostático, síndrome complejo regional 3,7 por ciento, el tamaño del efecto (EZ) fue de 1,2 el NNT= 4, a la 3ra semana se incrementó el dolor incidental e irruptivo, a partir del 10º día disminuyeron los efectos secundarios, como la somnolencia y nausea. Discusión y conclusiones: la osteoartritis, el síndrome de columna fallida, conducto lumbar estrecho mixto, síndrome complejo regional, secuelas de fracturas, prótesis fallidas, secuelas de displasia del desarrollo de la cadera, síndrome doloroso lumbar crónico, son padecimientos musculoesqueléticos en el que se aceptan el manejo de opiodes clase 3 de la OMS, de libración prolongada, como la buprenorfina...

Objetive: being the international year of the pain skeletal muscle, it is important to avoid the sub treatment, dice the prevalence of chronic pain, with the costs, functional limitation and diminution of the quality of life in the orthopedic patient requiring itself of less invasive routes as it is it the transdermal administration through matrix system of buprenorfina, on the basis of his high lip solubility without risk of hiperalgesia nor affectation of inmune system, considering his effect ceiling in respiratory depression, and its use in renal and hepatic comorbidity. Material and methodology: longitudinal, prospective study, randomized, of September of the 2008 to February 2010, in the service of algology of Orthocaz unit of N= orthopedics 108 both sexes, under informed consent. Results: Prevalence of pain in external consultation of orthopedics r= 60-80 per cent, x =70, the chronic greater nociceptive of 30 percent and neurophatic 1,5 percent with predominance in 53,8 percent feminine sex etiology the syndrome of insolvent column occupies 40,7 percent, osteoartrosis 44,4 percent, X= age 66,59 years, r= 20-85, secondary chronic neuropathic pain to metastasis in 3,7 lumbar column the cause most common prostate cancer, regional complex syndrome 3,7 percent the size of effect (EZ) the EU of 1,2 NNT= 4, to third week increase the incidental and irruptive pain, from the 10 day diminished the indirect effect, as drowsiness and feels nauseous. Discussion and and conclusions osteoarthritis, syndrome of insolvent column, lumbar conduit narrow compound, regional complex syndrome, sequels of fractures, prosthesis insolvent, sequels of dysplasia of the developement of the hip, chronic lumbar painful syndrome, are sufferings skeletal muscle in wich the handing of opiods is accepted class III, of the WHO of liberation prolonged as it is it buprenorfina transdermal, wih progressive degree, and to allow tolerability.