EULAR evidence-based recommendations for the management of fibromyalgia syndrome.

OBJECTIVE: To develop evidence-based recommendations for the management of fibromyalgia syndrome. METHODS: A multidisciplinary task force was formed representing 11 European countries. The design of the study, including search strategy, participants, interventions, outcome measures, data collection and analytical method, was defined at the outset. A systematic review was undertaken with the keywords "fibromyalgia", "treatment or management" and "trial". Studies were excluded if they did not utilise the American College of Rheumatology classification criteria, were not clinical trials, or included patients with chronic fatigue syndrome or myalgic encephalomyelitis. Primary outcome measures were change in pain assessed by visual analogue scale and fibromyalgia impact questionnaire. The quality of the studies was categorised based on randomisation, blinding and allocation concealment. Only the highest quality studies were used to base recommendations on. When there was insufficient evidence from the literature, a Delphi process was used to provide basis for recommendation. RESULTS: 146 studies were eligible for the review. 39 pharmacological intervention studies and 59 non-pharmacological were included in the final recommendation summary tables once those of a lower quality or with insufficient data were separated. The categories of treatment identified were antidepressants, analgesics, and "other pharmacological" and exercise, cognitive behavioural therapy, education, dietary interventions and "other non-pharmacological". In many studies sample size was small and the quality of the study was insufficient for strong recommendations to be made. CONCLUSIONS: Nine recommendations for the management of fibromyalgia syndrome were developed using a systematic review and expert consensus.

Partial protection against hyperbaric oxygen induced convulsions by dopaminergic agents in mice: possible involvement of autoreceptors?

In the present report we have investigated the effects of apomorphine, (-)3-PPP, L-DOPA and haloperidol on the elicitation of convulsions induced in mice by exposure to oxygen at high pressure (HBO) (5 ata O2). It was found that the administration of apomorphine (0.025-0.1 mg X kg-1 s.c.), (-)3-PPP (4 mg X kg-1 i.p.) L-DOPA (200-400 mg X kg-1 i.p.) as well as haloperidol (0.25-2.0 mg X kg-1 i.p.) produced a significant protection against HBO-induced convulsions. Haloperidol was the only drug to produce a dose-dependent decrease in respiration, and this effect does probably explain the anticonvulsant effects observed. The low doses at which apomorphine was effective, and the effects produced by (-)3-PPP, indicate an effect mediated via DA autoreceptors. Alternatively, and more likely taking the effects of L-DOPA into account, the DA receptors involved are sensitive enough to disclose postsynaptic agonist properties of apomorphine and (-)3-PPP at the doses employed.

Amphetamine as a protective agent against oxygen-induced convulsions in mice.

Male mice exposed to hyperbaric oxygen (HBO) at 4.5 ATA O2 exhibit a number of toxic symptoms including convulsions, diminished respiration and an acoustic reaction controlled by the central nervous system. To study whether stimulation of the nervous system could offer protection against the convulsions, mice were injected i.p. with various doses of d-amphetamine before HBO. At a dose of 1.0 mg X kg-1 of d-amphetamine the mice could stay at 5 ATA O2 without convulsions about three times as long as those injected with saline only. At high doses, 4 and 8 mg X kg-1, there was a weak protective effect or the time to convulsions was shortened. Amphetamine increases the release of dopamine in the brain and it is possible that the mechanisms of protection against HBO induced convulsions are involved in that process. The degree of protection, however, depends on the dose; therefore, it also is supposed that amphetamine in low doses acts on the autoreceptors with a presynaptic effect, which in this case is protective against the convulsions without affecting the respiration.

Central 5-HT and the respiratory response to acoustic stimulation in awake rats: effects of PCPA, 5-HTP and 8-OH-DPAT.

It was found that PCPA (4 X 50-100 mg/kg) decreased the respiratory response to tone pulses (acoustic reaction), and this effect was antagonized by the administration of 5-HTP (25 mg/kg), after inhibition of extracerebral aromatic amino acid decarboxylase by means of benserazide (25 mg/kg). A further increase in the dose of 5-HTP, 50-100 mg/kg, in animals not treated with PCPA did not significantly affect the acoustic reaction. The putative 5-HT agonist 8-OH-DPAT produced a decrease in the acoustic reaction (but also at higher doses some desynchronization of respiration with tone). The administration of d-amphetamine, 0.5-2.0 mg/kg, resulted in an increase in the acoustic reaction. Thus, in the present experiment, using a simple sensory-motor response, 8-OH-DPAT behaves as a 5-HT antagonist and the results provide further support for mixed 5-HT receptor agonist/antagonist properties of this compound.