Mario Tiengo

Dynamics and significance of placebo response in primary dysmenorrhea.

&NA; A total of 55 patients with primary dysmenorrhea who had shown a favorable response to a preliminary treatment cycle with placebo were admitted to a double‐blind study on placebo versus antiprostaglandin agents (naproxen and pirprofen). To evaluate the placebo effect and its duration, the treatment was given for 4 successive cycles. Whereas the antiprostaglandin agents were effective in most of the patients (in 80% of the pirprofen group and 85.7% of the naproxen group) and this efficacy was maintained throughout the study, a favorable response to placebo was observed in 84% in the first cycle, 29% in the second, 16% in the third and 10% in the fourth. The incidence of side effects was similar in the placebo and the active treatment groups (35.4% vs. 37.5%). It is postulated that a placebo effect in dysmenorrhea is due to a central analgesic mechanism mediated by endorphin release or possibly to psychological dynamics (mental or conditioning theories). However, this effect loses efficacy with time possibly due to a decreased susceptibility to the opioid action of the central nervous circuits responsible for menstrual pain perception or to deconditioning mechanisms.

Pattern-reversal visual evoked potentials and EEG correlations in common migraine patients

SYNOPSIS

The effect of somatostatin on experimental inflammation in rats

The aim of the present study was to investigate the effect of somatostatin administration on experimentally induced inflammation in rats.Inflammation was induced by the intraplantar injection of carrageenan (50 micro L) into the hind paw of the rat. Animals were treated intraplantarly with somatostatin in a volume of 50 micro L at different doses (2.5, 25, and 250 ng, 10 micro g). The inflammatory response was studied 120, 180, and 240 min after drug administration. The antinociceptive effect of somatostatin was determined by using the Randall and Selitto test and by local production of beta-endorphin from lymphocytes obtained from popliteal lymph nodes. Data show that small doses of somatostatin were the most effective in reducing hyperalgesia. Moreover, our results show that somatostatin treatment significantly increased beta-endorphin in lymphocytes from popliteal lymph nodes. The secretion of opioid peptides, which enhance analgesia, could be stimulated by locally administered somatostatin. Implications: Acute pain because of intraplantar inflammation induced in rats by carrageenan injection was significantly reduced by small-dose, local administration of somatostatin, which possibly favors beta-endorphin release as a mechanism. These results may have implications regarding treatment of pain conditions associated with an inflammatory response. (Anesth Analg 1997;85:1112-5)

Pattern reversal visual evoked potentials (VEP-PR) in migraine subjects with visual aura.

SYNOPSIS

Dermorphin, a new peptide from amphibian skin, inhibits the nociceptive thalamic neurons firing rate evoked by noxious stimuli

Dermorphin is the representative of a new class of potent opioid peptides occurring in amphibian skin and possesses the unique feature of having a D-Ala residue incorporated in the peptide molecule. The effect of dermorphin on the spontaneous and evoked neuronal activity by a nociceptive stimulus was studied in the nucleus lateralis anterior and ventrobasal complex of the rat thalamus. The high firing frequency induced by nociceptive stimuli was blocked when dermorphin was injected intraperitoneally at the dose of 1.5 mg/kg. The action starts about 10 min after injection and lasts on average for 120 min. Naloxone, a specific opioid antagonist, injected i.p. at a dose of 1 mg/kg antagonized the effect of dermorphin. The dermorphin time-course is about twice that of morphine (1.5 mg/kg i.p.) under the same experimental conditions.

Pain, analgesia, and stress: an integrated view.

The different theories on the neuroanatomical substrate of pain have been revised in the frame of new concepts on the intercellular communication in the central nervous system. In fact, it has recently been proposed that two kinds of electrochemical transmission exist in the brain: the first one, called wiring transmission (WT), uses neuronal chains (neuronal plasma membranes and synaptic contacts), whereas the second one, called volume transmission (VT), uses the extracellular fluid as physical substrate. The old concept of a separate system of afferents and central cells that constitute the pain mechanism is no more longer tenable. To reach a better understanding of the psychophysiological basis of pain, we should consider a view where WT and VT cooperate within neuronal systems functionally affected by the pervading modulatory action of endocrine signals.

Centrally administered neuropeptide Y fails to increase food intake but enhances hypoalgesia in spontaneously hypertensive rats

The effects of intracerebroventricular (i.c.v.) administration of neuropeptide Y (NPY1-36) on food intake and pain sensitivity in hot plate test were studied in spontaneously hypertensive rats (SHRs) and in normotensive Wistar-Kyoto (WKy) rats. In satiated SHRs NPY1-36 failed to significantly increase intake at doses that produced a strong effect in satiated WKy rats (0.25-1.25 nmol). Conversely, both NPY1-36 and the C-terminal fragment NPY13-36, a putative selective agonist for the Y2-receptor for NPY, enhanced the spontaneously occurring hypoalgesia of SHRs, having no effect in WKy rats. The present results indicate that the NPY central systems involved in the control of regulatory functions are differently tuned in SHRs and WKy rats, suggesting possible involvement of these systems in the genesis of hypertension.

Effect of somatostatin on β-endorphin release in rat experimental chronic inflammation

The aim of the present study was to investigate the effect of somatostatin administration in arthritic rats. Inflammation was induced by daily interplantar injection of 100 microl of Freunds complete adjuvant into the left hind paw of the rat. Arthritis developed 20 days following the first injection and was stable in the inoculate paw. Arthritic rats were treated interplantarly with somatostatin (5 or 10 microg) or with indomethacin (100 microg) daily for 14 days. Inflammatory response was studied at 12 h, 7 and 14 days following drug administration. The effect of somatostatin was determined by local (into popliteal lymph nodes) and systemic production of beta-endorphin. Our results showed that somatostatin treatment significantly increased beta-endorphin levels in the blood and lymphocytes from popliteal lymph nodes. Greater efficiency was seen when 5 microg instead of 10 microg of somatostatin was used. A significant decrease of absolute leukocytosis was observed at the 14th day following somatostatin administration. Moreover, a significant reduction of plasmatic beta-globulins at 12 h and the 7th day and of plasmatic alpha2-globulins at the 14th day was observed after the beginning of somatostatin treatment.

Depressant effects of suprofen, a new non-steroidal anti-inflammatory drug on thalamic evoked neuronal firing in arthritic rats

The effects of suprofen, a new non-steroidal anti-inflammatory drug, (NSAID), the activity of which is mainly antinociceptive, were compared with those of aspirin (as a reference drug) in a study of spontaneous and evoked firing of thalamic neurons (nucleus lateralis and ventrobasalis) in rats rendered arthritic by injection of Freunds adjuvant into the paw. Suprofen (3.7 mg/kg, i.v.) induced a marked decrease in the firing evoked in arthritic rats by ankle mobilization. This effect, after a rapid onset, lasted on the average for 60 min. A similar effect was obtained with aspirin, but with 54 mg/kg (i.v.) (14 times more than suprofen). With increasing doses of suprofen, it was possible to obtain an increased long-lasting inhibition of the evoked activity, with a significant dose-effect linear regression. The possibility that there are both CNS and peripheral effects of suprofen is discussed in relation to the possible role of aspirin (the reference standard for NSAIDs) in enhancing presynaptic inhibition, thus reducing the effectiveness of incoming sensory stimuli.

Inhibitory effect of eseroline, an opiate like drug, on the rat nociceptive thalamic neurons activated by peripheral noxious stimuli

Eseroline is a new agent, derived from physostigmine but lacking in pseudocholinesterase activity, that possesses opioid properties in vivo and in vitro in cats and rodents. The electrophysiological effect of this drug has been investigated. Our findings show that Eseroline (5 mg/kg i.p.), suppresses the nociceptive responses evoked by noxious (mechanical and thermal) stimuli, without affecting the spontaneous firing of neurons in the thalamus of anesthetized rat. This effect starts about 5 min after the administration and lasts on average for about 60 min. Naloxone (1 mg/kg i.p.), injected 10 min before Eseroline, antagonized the antinociceptive action of this drug.