Comparative Investigation of Five Cobras’ Venoms Analgesic Capacity

Every day, a lot of people suffer from different types and intensity pain. Pain is probably the most common symptomatic reason to seek medical consultation. Unfortunately, despite improved knowledge of underlying mechanisms and better treatments, many people who have any type of pain receive inadequate care and non-effective drugs. Although the pain transmission channels are intensively studied, and the drug market is constantly replenished with new analgesics, it is well known that existing medications for the treatment of pain are often associated with serious side effects and rapid development of tolerance (moderate efficiency, physical dependence, respiratory arrest, suffocation, cardiac arrest, etc.). Thus, there is a need for new, more effective remedies. For this reason, despite the presence of a large number of anti-pain drugs, research and development of more effective and safe means for anaesthesia continue. Natural resources, particularly venoms, are a perspective supplier of antinociceptive and anti-inflammatory medicines. Venoms are complex mixtures of bioactive substances with high selectivity for physiological processes, including modulation of different ion channels, receptors function, and metabolic pathways. Thus, venoms represent an extensive source of molecules for the development of therapeutic agents. The goal of this study was the comparison of antinociceptive effects of five different cobras' venom antinociceptive action of cobras’ venoms was carried out under the same experimental conditions, at the same doses, during acute and inflammatory pain in mice in “formalin test”. To avoid toxic effects, the sublethal dose of each cobra venom (approximately 1/10 LD 50 ) was selected. The behavioural study showed that all tested venoms had a slight sensitizing effect in the acute phase during the first 5 min. In the second, inflammatory phase (16*25min), all tested cobra’s venoms (3μg/0.1ml, intraperitoneal) showed significant antinociceptive action, particularly the Naja naja oxiana venom decreased pain sensitivity by 48.4%, the Naja naja pallida venom by 75.4%, the Naja naja nigricincta venom by 38.5%, the Naja naja kaouthia venom by 33.2%, and the Ophiophagus Hannah venom by 78.3%, (p<0.05). The analgesic capacity of Analgin and Diclofenac under the same conditions were 77.9% and 88.7%, respectively. Thus, the Naja n. pallida and Ophiophagus Hannah venoms have shown the most expressed antinociceptive action, and they have competitive effectiveness compared to classic analgesics. They may be chosen as the most effective from tested venoms for further development of pain relief remedies.

Analgesic Interaction Between Morphine with Fentanyl In Experimental Murine Pain

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.

Analgesic and anti-inflammatory activity of Artemisia extracts on animal models of nociception

Introduction. The study aims to assess the antinociceptive and anti-inflammatory activity of extracts obtained from indigenous species of wormwood: Artemisia absinthium, A. annua, A. vulgaris and A. pontica. Materials and methods. For these experiments, we employed nociception models using thermal stimulus (hot plate and tail immersion tests, t = 52.5 0C; 30, 60 and 90 minutes testing), chemical stimulus (Zymosan-induced abdominal constriction response test, using distinct lots and testing at 60, 90 and 120 minutes after administration of samples) and pressure stimulus (Randall Selitto test) and an inflammation model for the evaluation of inflammatory edema by Plethysmometer test. Groups of 6 Swiss mice / lot were used, receiving by oral administration the plant extracts suspended in 0.1% CMC-Na. The doses were administered in geometric progression. Chemical analyses were performed by HPLC-MS in order to identify bioactive substances present in extracts: methoxylated flavonoids, sesquiterpene lactones, phytosterols and hydroxycinnamic acids. Results and discussion. All plant extracts showed antinociceptive action on the models with thermal stimulus, as demonstrated by the ED50 values obtained at different test times. In the models of nociception with chemical and mechanical stimulus, models based on inflammatory mediation, the studied fractions have partially proved their antinociceptive action. Regarding the degree of inhibition of inflammatory edema, the highest potency was exhibited by Artemisia pontica extract (86.5% inhibition for the dose of 100 mg/kg). Hispidulin and eupatorin, known anti-inflammatory compounds, were identified in all extracts, along with caffeic and chlorogenic acids, stigmasterol, campesterol and β-sitosterol. Conclusions. The obtained results support the use of these plant extracts in moderate intensity pain, triggered by both central and peripheral mechanisms. Keywords: hot-plate test, tail immersion test, abdominal constrictive response, Randall-Selitto test, inflammatory edema,

Magnesium and Pain

In terms of antinociceptive action, the main mode of action of magnesium involves its antagonist action at the N-methyl-d-aspartate (NMDA) receptor, which prevents central sensitization and attenuates preexisting pain hypersensitivity. Given the pivotal function of NMDA receptors in pain transduction, magnesium has been investigated in a variety of pain conditions. The oral and parenteral administration of magnesium via the intravenous, intrathecal, or epidural route may alleviate pain and perioperative anesthetic and analgesic requirements. These beneficial effects of magnesium therapy have also been reported in patients with neuropathic pain, such as malignancy-related neurologic symptoms, diabetic neuropathy, postherpetic neuralgia, and chemotherapy-induced peripheral neuropathy. In addition, magnesium treatment is reportedly able to alleviate fibromyalgia, dysmenorrhea, headaches, and acute migraine attacks. Although magnesium plays an evolving role in pain management, better understanding of the mechanism underlying its antinociceptive action and additional clinical studies is required to clarify its role as an adjuvant analgesic.