Anti-hyperalgesic effect of Lippia grata leaf essential oil complexed with ß-cyclodextrin in a chronic musculoskeletal pain animal model: Complemented with a molecular docking and antioxidant screening.

BACKGROUND: Due to its unclear pathophysiology, the pharmacological treatment of fibromyalgia is a challenge for researchers. Studies using medicinal plants, such as those from the genus Lippia, complexed with cyclodextrins (CDs) have shown innovative results. OBJECTIVE: The present research intended to evaluate the effect of an inclusion complex containing ß-cyclodextrin (ßCD) inclusion complex with Lippia grata (LG) essential oil in a chronic musculoskeletal pain model, its central activity and its possible interaction with neurotransmitters involved in pain. METHODS: After acid saline-induced chronic muscle pain, male mice were evaluated for primary and secondary hyperalgesia and muscle strength. Moreover, an antagonist assay was performed to assess the possible involvement of the opioidergic, serotonergic and noradrenergic pathways. In addition, Fos protein in the spinal cord was assessed, and a docking study and antioxidant assays were performed. RESULTS: The treatment with LG-ßCD, especially in the dose of 24mg/kg, was able to significantly decrease (p<0.05) the paw withdrawal and muscle threshold. Furthermore, LG-ßCD was shown to affect the opioidergic and serotonergic pathways. There were no significant changes in muscle strength. Fos protein immunofluorescence showed a significant decrease in expression in the dorsal horn of the spinal cord. The main compounds of LG showed through the docking study interaction energies with the alpha-adrenergic and µOpioid receptors. In all antioxidant assays, LG exhibited stronger antioxidant activities than LG-ßCD. CONCLUSION: This study suggested that LG-ßCD could be considered as a valuable source for designing new drugs in the treatment of chronic pain, especially musculoskeletal pain.

State of the science: hot flashes and cancer. Part 2: management and future directions.

PURPOSE/OBJECTIVES: To critically evaluate and synthesize intervention research related to hot flashes in the context of cancer and to identify implications and future directions for policy, research, and practice. DATA SOURCES: Published, peer-reviewed articles and textbooks; editorials; and computerized databases. DATA SYNTHESIS: Although a variety of pharmacologic and nonpharmacologic treatments are available, they may not be appropriate or effective for all individuals. CONCLUSIONS: The large and diverse evidence base and current national attention on hot flash treatment highlight the importance of the symptom to healthcare professionals, including oncology nurses. IMPLICATIONS FOR NURSING: Using existing research to understand, assess, and manage hot flashes in the context of cancer can prevent patient discomfort and improve the delivery of evidence-based care.

Alternatives to estrogen.

For many years, women have sought alternative therapies for menopausal symptoms and for general health overall. The highly publicized findings from the Women's Health Initiative have led to an increased pressure on the medical community to find safe and alternative medications for female health. This article reviews the challenges and problems with the use of alternative medicines, and the clinical trials that prove their efficacy, and discusses the safety issues that may occur with these types of products.

[Treatment of cluster headache]. / Le traitement de l'algie vasculaire de la face.

INTRODUCTION: The cluster headache (CH) is one of the most severe types of head pain. It is a typical example of a periodic disease and the International Headache Society classification recognizes two forms of this disease: episodic and chronic CH. Its prevalence is about 0.1 to 0.4% in the general population. PATHOPHYSIOLOGY: A global hypothesis is still lacking to explain the pain, the vasodilation, the autonomic features (ipsilateral lacrimation, conjunctiva injection, rhinorrhea, partial Horner syndrome, etc.) and the periodicity of the CH. Pain and vasodilation seem secondary to an activation of the trigeminal vascular system and the periodicity of the attacks is thought to be due to a dysfunction of hypothalamic biologic clock mechanisms. Treatment of acute CH attacks. The most effective agents are oxygen inhalation and subcutaneous sumatriptan, a 5HT1B and D receptor agonist which has vasoconstrictor and anti-neurogenic inflammation properties by blocking the release from the trigeminal-sensitive fibers of neuropeptides such as CGRP and substance P. With subcutaneous sumatriptan, headache relief is very rapid, within 5 to 10 min. Prophylactic treatment of CH: The number of attacks per day varies from one to three, but some patients can have four to eight per day and acute treatments fail to provide sufficient relief or give rise to side-effects. Several different regimens have been proven effective. FUTURE PROSPECTS AND PROJECTS: Contraindications and side-effects of the drugs limit the choice of the prophylactic treatment: corticosteroids in a tapering course, verapamil and methysergide are the most useful treatments of the episodic form. Lithium carbonate is more effective for the chronic stage of CH, but side-effects are often troublesome. Numerous other medications have been used for prophylaxis: valproate, capsaicin, beta-blockers. Unfortunately, double-blind studies are often lacking and are difficult to realize due to spontaneous variable remission of episodic CH. When adequate trials of drug therapies show a total resistance to the treatments, surgery may be considered. Radiofrequency trigeminal rhizotomy is the treatment of choice with 70% of beneficial effects. Risks and complications have to be discussed in balance with the benefit of the different surgical procedures.

Management of hot flashes in breast-cancer survivors.

Hot flashes can be a major problem for patients with a history of breast cancer. Although oestrogen can alleviate hot flashes to a large extent in most patients, there has been debate about the safety of oestrogen use in survivors of breast cancer. The decrease in hot flashes achieved with progestational agents is similar to that seen with oestrogen therapy but, again, there is some debate about the safety of progestational agents in patients with a history of breast cancer. Several alternative substances have therefore been investigated. These include a belladonna alkaloid preparation, clonidine, soy phyto-oestrogens, vitamin E, gabapentin, and several of the newer antidepressants, with venlafaxine being the best studied to date. Several studies in progress may provide better non-hormonal means of treating hot flashes in the future.

[The effect of tropoxin on the neurogenic and vasogenic inflammation of the dura mater vessels]. / Vliianie tropoksina na neirogennoe i vazogennoe vospalenie sosudov tverdoi mozgovoi obolochki.

Subchronic administration of tropoxin (in doses of 7.5 and 10 mg/kg) caused dose-dependent blocking of 131I-albumin plasma transudation from the dura mater vessels, induced by electrical stimulation of the trigeminal ganglion and intravenous infusion of the agonist of 5-HT2B/2C receptors metachlorophenylpiperazine. The antimigraine agent metisergid produced a similar effect. A single injection of metisergid and tropoxin did not block albumin transudation. A 3 mg/kg dose of mianserin prevented the blocking effect of tropoxin and metisergid on plasma exudation into the dura mater. It is suggested that the mechanism of the tropoxin antimigraine effect is realized through the presynaptic 5-HT1 receptors of afferent endings of the trigeminal nerve and the postsynaptic 5-HT2B/2C receptors of the dura mater vessels.

Migraine polypharmacy and the tolerability of sumatriptan: a large-scale, prospective study.

Polypharmacy (the prescription of more than one therapy for a single patient) and subcutaneous (s.c.) sumatriptan tolerability were prospectively studied in 12,339 migraineurs, each followed for up to 1 year. Inclusion/exclusion criteria were minimal and mirrored United States Imitrex labeling. Drug usage and compliance monitoring were automatically interfaced with prescription refill. Concomitant drugs were used by 79% of patients, with analgesics, antidepressants, and sedatives used most commonly. No adverse interactions between sumatriptan and neurological drugs were found, possibly reflecting relative inability of the former to cross the blood-brain barrier. No difference in cardiovascular adverse events was associated with oral contraceptive use, which was more common than expected. No other drug class influenced adverse event probability, although sample sizes for these comparisons was sometimes <400 patients. This study confirms the prevalence of polypharmacy in migraine, identifies the drugs used, and concludes that, on a population basis, the tolerability of s.c. sumatriptan, when used according to labeled instructions, is unaffected by these concomitant drugs.

Nonestrogen management of menopausal symptoms.

Women who cannot or choose not to take estrogens do have alternatives; however, the options are few and unproven in longterm clinical trials with respect to safety and efficacy. Many available alternative treatments may alleviate the symptoms of the menopause, but do not convey long-term protection against osteoporosis and cardiovascular disease. This article reviews treatment alternatives to estrogen replacement therapy for symptomatic relief.

Involvement of 5-hydroxytryptamine and bradykinin in the hyperalgesia induced in rats by collagenase from Clostridium histolyticum.

The involvement of bradykinin, 5-hydroxytryptamine, substance P and prostanoids in the hyperalgesia elicited by collagenase in rat paw was investigated. Collagenase (100 micrograms) induced a slight hyperalgesia in kininogen deficient rats in comparison with the behavioural response obtained in normal rats. Lisinopril (10(-5) M), and angiotensin-converting enzyme inhibitor, increased the duration of the hyperalgesia elicited in normal rats. Ondansetron (0.5 to 5 mumol/kg), a 5-HT3 antagonist, suppressed the hyperalgesia as did methysergide (1.1 to 11 mumol/kg), a mixed 5-HT1 and 5-HT2 receptor antagonist. However, the hyperalgesia was not modified by RP 67580 (1.8 to 18 mumol/kg), a NK1 receptor antagonist, and was only slightly delayed by indomethacin (2 mg/kg), a cyclo-oxygenase inhibitor. The oedema-promoting effect of 5-HT (6 nmol) was inhibited by methysergide but not by ondansetron. The swelling induced by collagenase in rat paw was reduced by methysergide but not by ondansetron. We conclude that the behavioural response induced by collagenase depends on an interactions between bradykinin and 5-HT. Prostanoids play a minor role in the beginning of the reaction whereas substance P is not significantly involved in this hyperalgesia.

Cluster headache presenting with orbital inflammation.

Acute, noninfectious orbital inflammations often defy a specific diagnosis despite a thorough medical evaluation and are grouped in the nonspecific diagnostic category of idiopathic inflammation of the orbit (pseudotumor). An atypical case of cluster headache presenting with intermittent migratory facial swelling and orbital inflammation, and 3 mm of exophthalmos simulating idiopathic orbital inflammation is presented. Although periobital pain is a frequent finding in patients suffering from cluster headaches, to the authors' knowledge this is the first reported case of orbital inflammation with cluster headache. After unsuccessful treatment directed at potential infectious and inflammatory causes, the patient responded well to methysergide, an established treatment for cluster headaches. A review of the known mechanism for this disorder, peripheral and central nervous system mechanisms of pain, and migratory angioedema reveals overlapping pathophysiology, clinical findings, and associated symptoms.

Collagenase-induced oedema in the rat paw and the kinin system.

Collagenase (100 micrograms) induced a large plasma extravasation, during the first 15 min after its injection in rat paw, associated with the rapid development of oedema which subsided after 6 h. The extent of the oedema was similar in normal and kininogen-deficient rats. The swelling induced in normal rats was reduced by HOE 140 (D-Arg[Hyp3,Thi5,D-Tic7,Oic8]bradykinin), a bradykinin B2 receptor antagonist, and by three serine protease inhibitors, soybean trypsin inhibitor (SBTI), Leucaena leucocephala trypsin inhibitor 1 (LLTI-1) and Leucaena leucocephala trypsin inhibitor 2 (LLTI-2). These agents had no effect on the oedema induced in kininogen-deficient rats. The swelling was also reduced by methysergide, indomethacin, ketoprofen and methylprednisolone. It was increased by heparin, but it was not modified by mepyramine, WEB 2086 (3-[4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]-triazolo- [4,3-a][1,4]-diazepine-2-yl]-1-(4-morpholinyl)-1-propanone) and NG-nitro-L-arginine. In vitro, collagenase did not release kinins from rat plasma or from purified T-kininogen. LLTI-1 and LLTI-2 did not inhibit collagenase activity for one of its specific substrates. Kinins are thus involved in the development of collagenase oedema in normal rats. Their generation would be indirect following changes in matrix proteins in extravascular spaces. Nevertheless, kinins are not the decisive mediators of the swelling. Serotonin, possibly released from platelets, and prostanoids participate in the inflammatory process.

Hot flashes--physiology, hormonal therapy, and alternative therapies.

Hormone replacement therapy should be discussed with every postmenopausal woman and should be the first therapy offered to treat hot flashes owing to its high efficacy and other beneficial properties. Women who are ineligible for or uncomfortable with estrogen replacement therapy and who suffer from hot flashes that interfere with the quality of life should be offered other regimens as discussed in this article.

Enxaqueca: revisäo / Migraine: a review

A enxaqueca tem sido citada na literatura médica por mais de 2000 anos, desde antes do começo da era cristä. É a causa mais frequente de cefaléia em nosso meio. Neste sentido procuramos fazer uma revisäo da migrânea abordando desde o histórico, classificaçäo, fisiopatologia, até o tratamento

Chronic cluster headache managed by nervus intermedius section.

Cluster headache sufferers who become candidates for surgical treatment are those relatively rare patients who are refractory to all attempts at pharmacological relief. Ablative surgical procedures have been directed against either the trigeminal nerve or the nervus intermedius/greater superficial petrosal (NI/GSP) pathway. Both carry nociceptive impulses from the head and face, and the NI also carries parasympathetic fibres which appear to be responsible for the autonomic concomitants of cluster headache. Trigeminal operative procedures are not consistently helpful in chronic cluster headache, while NI section has been shown to give potentially long lasting relief but carries the potential risks of cerebellopontine angle surgery. In eight selected cases of chronic cluster headache we have demonstrated a high early success rate for pain relief, with few complications, in the performance of NI section, combined, when indicated, with microvascular decompression of the trigeminal main sensory root. We believe that cochlear nerve monitoring helps prevent postoperative hearing impairment. An intimate relationship between the NI and arterial loops of the anterior inferior cerebellar artery (AICA) or the internal auditory artery has been frequently observed in our chronic cluster headache patients.

Serotonin antagonists.

The realisation that serotonin plays a role not only in the carcinoid syndrome but also in migraine, nociception, dumping syndrome, vascular disease and hypertension, has led to an enormous amount of activity in search of serotonin antagonists. Numerous such pharmacological agents have been identified but only few have found their way into clinical use. All of them are competitive serotonin inhibitors, in that they vie for the same receptor as the amine itself and are thus able to block its action as well as imitate its effects. By far the widest use of such inhibitors is in the prevention of migraine, where they have effectively eliminated the dread of an attack from the life of the majority of patients. Whilst useful in the control of diarrhea in patients with carcinoid and dumping syndromes, their role in these diseases is limited. However, the possible role of serotonin in hypertension and nociception opens new avenues in the use of existing serotonin antagonists and calls for the discovery of a new generation of such pharmacological agents for the control of these conditions.

Inflammatory pleuropulmonary fibrosis in essential fatty acid deficient rats and the lack of response to methysergide.

In view of the association between essential fatty acid (EFA) deficiency and human cystic fibrosis, we have investigated the possible occurrence of pulmonary disease in rats fed an EFA deficient (EFAD) diet for 40 weeks. In contrast to a few slight spontaneous lesions consisting of pleural membrane hyperplasia, which were found in the lungs of control rats, a much greater incidence of fibrotic lesions was observed in the lungs of EFAD rats. These pleuropulmonary fibroses extended from the hyperplastic pleural membrane into the alveoli and were characterized by collagen deposition and marked macrophage infiltration to the extent that, in some cases, the alveolar septa were completely obstructed by inflammatory exudate. These findings lend indirect support to the contention that EFA deficiency plays a role in the aetiology of cystic fibrosis, at least with regard to pulmonary lesions. Administration of methysergide (10 mg/kg/day, p.o.) for a total of 11 weeks, did not alter the incidence of fibrosis in the lungs of EFAD rats, despite the finding that a man who had developed pleuropulmonary fibrosis as a result of chronic methysergide treatment exhibited a relative serum EFA deficiency. While a relative EFA deficiency may be a predisposing factor for the induction of fibrosis by chronic methysergide treatment, our data are not sufficient to make a decision upon this hypothesis.