Cannabis has been used for medicinal purposes for thousands of years. The prohibition of cannabis in the middle of the 20th century has arrested cannabis research. In recent years there is a growing debate about the use of cannabis for medical purposes. The term ‘medical cannabis’ refers to physician-recommended use of the cannabis plant and its components, called cannabinoids, to treat disease or improve symptoms. Chronic pain is the most commonly cited reason for using medical cannabis. Cannabinoids act via cannabinoid receptors, but they also affect the activities of many other receptors, ion channels and enzymes. Preclinical studies in animals using both pharmacological and genetic approaches have increased our understanding of the mechanisms of cannabinoid-induced analgesia and provided therapeutical strategies for treating pain in humans. The mechanisms of the analgesic effect of cannabinoids include inhibition of the release of neurotransmitters and neuropeptides from presynaptic nerve endings, modulation of postsynaptic neuron excitability, activation of descending inhibitory pain pathways, and reduction of neural inflammation. Recent meta-analyses of clinical trials that have examined the use of medical cannabis in chronic pain present a moderate amount of evidence that cannabis/cannabinoids exhibit analgesic activity, especially in neuropathic pain. The main limitations of these studies are short treatment duration, small numbers of patients, heterogeneous patient populations, examination of different cannabinoids, different doses, the use of different efficacy endpoints, as well as modest observable effects. Adverse effects in the short-term medical use of cannabis are generally mild to moderate, well tolerated and transient. However, there are scant data regarding the long-term safety of medical cannabis use. Larger well-designed studies of longer duration are mandatory to determine the long-term efficacy and long-term safety of cannabis/cannabinoids and to provide definitive answers to physicians and patients regarding the risk and benefits of its use in the treatment of pain. In conclusion, the evidence from current research supports the use of medical cannabis in the treatment of chronic pain in adults. Careful follow-up and monitoring of patients using cannabis/cannabinoids are mandatory.
This study investigated whether systemic magnesium sulfate (an antagonist at the glutamate subtype of N-methyl-D-aspartate receptor) affects inflammatory pain, and whether the nitric oxide pathway is involved. Carrageenan (0.5%, 0.1 mL, intraplantar)-induced mechanical hyperalgesia was evaluated using the electronic von Frey test in male Wistar rats. Magnesium sulfate had no effect when injected locally into the inflamed rat paw. However, subcutaneous magnesium sulfate, at doses of 0.5, 5, 15 and 30 mg/kg, reduced the hyperalgesia by 44.4 ± 8.8, 68 ± 8.4, 24.6 ± 6.9 and 45.3 ± 6.7% respectively. N-nitro-L-arginine methyl ester hydrochloride (L-NAME) (3 and 5 mg/kg, intraperitoneal), a non-selective nitric oxide synthase inhibitor, significantly reduced the effects of magnesium sulfate. Also, L-arginine (0.4 mg/kg, subcutaneously) significantly reversed the effect of L-NAME in the magnesium sulfate-treated rats. A selective inhibitor of neuronal or inducible nitric oxide synthase, N-Propyl-L-arginine hydrochloride (L-NPA) (0.5, 1 and 2 mg/kg, intraperitoneal) and S-methylisothiourea (SMT) (0.005, 0.01 and 0.015 mg/kg, intraperitoneal) reduced the effect of magnesium sulfate significantly only at the highest doses tested. When given alone, L-NAME (3 and 5 mg/kg) L-NPA (2 mg/kg) and SMT (0.015 mg/kg) did not have any influence on carrageenaninduced hyperalgesia. The present study revealed that magnesium sulfate is effective against inflammatory pain after systemic, but not after local peripheral administration, and activation of the nitric oxide pathway is probably involved in the anti-hyperalgesic effect of magnesium sulfate. Low doses of systemic magnesium sulfate given as a pretreatment or a treatment might have a beneficial effect in patients with inflammatory somatic pain.
Pain is a common symptom in older people. It is possible that pain is underreported in older persons due to an incorrect belief that it is an inevitable part of aging. Opioid analgesics are potent medications, with confirmed efficacy for the treatment of moderate to severe pain. These drugs are commonly used in older persons. However, there is insufficient evidence regarding safety of opioids in older patients. One of the reasons for this is the lack of randomized, controlled clinical trials. People of advanced age often have comorbidites and use other prescription drugs, as well as over-the-counter (OTC) compounds, thus making them more suceptible to the risk of interactions with opioids. Significant pharmacokinetic and pharmacodynamic changes that occur with advancing age increase the risk of adverse effects of opioids. There are also some discrepancies between guidelines, which recommend the use of lower doses of opioids in older patients, and the findings in the literature which suggest that pain is often undertreated in this age group. It seems that there are significant variations in the tolerability of different opioid analgesics in older people. Morphine, fentanyl, oxycodone, and buprenorphine are still the preferred evidence-based choices for add-on opioid therapy for these patients. However, the safety and efficacy of other opioids in older patients, especially if comorbidities and polypharmacy are present, is still questionable. This review addresses the most important aspects of the use of opioids in older persons, focusing on pharmacokinetics, pharmacodynamics, adverse effects, and interactions.
It is necessary to improve the knowledge and attitudes of medical students towards pharmacotherapy of rare diseases. [Projekat Ministarstva nauke Republike Srbije, br. 175023]
Context: Magnesium and MK-801 (dizocilpine), antagonists of N-methyl-D-aspartate receptors, are involved in the processing of pain. Objective: This study determines whether magnesium sulfate (MS) and MK-801 affects visceral inflammatory pain and determines a possible mechanism of action. Materials and methods: Analgesic activity was assessed using the acetic acid-induced writhing test in rats. MS (1-45 mg/kg) or MK-801 (0.005-0.03 mg/kg) was administrated subcutaneously (s.c.). To assess possible mechanisms of action, we examined the effects of L-NAME (10 mg/kg, intraperitoneal), methylene blue (0.5 mg/kg, s.c.), and glibenclamide (3 mg/kg, s.c.) on the effect of MS or MK-801. Results: MS and MK-801 showed biphasic and linear dose-response pattern, respectively. MS reduces the number of writhing on the dose of 1, 5, and 15 mg/kg by 60, 50, and 78%, respectively, while it has no effects on the doses of 30 and 45 mg/kg. MK-801 (0.005-0.03 mg/kg) showed decrease in the number of writhing by 33-79%. The mean effective doses of MS and MK-801 were 6.6 (first phase) and 0.009 mg/kg, respectively. Both drugs did not impair the rotarod performance. L-NAME, methylene blue, and glybenclamide reduced the effect of MK-801 by 100, 43, and 64%, respectively, but not the effect of MS. Conclusions:The results suggest that MS and MK-801 may be useful analgesics in the management of visceral inflammatory pain, at doses that do not induce motor impairment. The modulation of NO/cGMP/K+ATP pathway plays an important role in the antinociceptive mechanism of MK-801, but does not contribute to the antinociceptive effect of MS.
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