Recently, the cannabinoid (CB) receptor agonist anandamide (AEA) has been shown to excite perivascular terminals of primary sensory neurons via activation of the vanilloid receptor-1 (VR-1). To determine whether AEA stimulates central terminals of these neurons, via VR-1 activation, we studied the release of calcitonin gene-related peptide (CGRP)-and substance P (SP)-like immunoreactivities (LI) from slices of rat dorsal spinal cord. Mobilization of Ca 2ϩ in rat dorsal root ganglion (DRG) neurons in culture was also studied. AEA (0.1-10 M) increased the outflow of CGRP-LI and SP-LI from slices of the rat dorsal spinal cord in a Ca 2ϩ -dependent manner and increased [Ca 2ϩ ] i in capsaicin-sensitive cultured DRG neurons. Both effects of AEA were abolished by capsaicin pretreatment and by the VR-1 antagonist capsazepine but not affected by the CB receptor antagonists AM281 or AM630. Both neuropeptide release and Ca 2ϩ mobilization induced by electrical field stimulation (EFS) were inhibited by a low concentration of AEA (10 nM). Inhibition by AEA of EFS-induced responses was reversed by AM281 and AM630, but was not affected by capsazepine. Results indicate that stimulation of VR-1 with high concentrations of AEA excites central terminals of capsaicin-sensitive DRG neurons, thus causing neuropeptide release in the dorsal spinal cord. This novel activity opposes the CB receptor-mediated inhibitory action of low concentrations AEA. However, only if large amounts of endogenous AEA could be produced at the level of the dorsal spinal cord, they may not inhibit, but rather activate, nociceptive sensory neurons.
We carried out an intensive incidence, prevalence, and mortality survey of motor neuron disease (MND) in the province of Ferrara, northern Italy. Based on 72 patients, the mean incidence per year for the period 1964 through 1982 was 0.98 cases per 100,000. On December 31, 1981, the prevalence rate was 3.95 per 100,000. In the 19-year period the average mortality rate was 0.83 per 100,000 per year. The disease was more common in men, in individuals aged 50 to 70 years, and in residents in rural areas engaged in agricultural work. A retrospective case-control study, confirming a significantly higher frequency of MND in farmers and persons living in rural areas, revealed that the disease was more common in the lower social classes to which most unskilled and heavy laborers belong. In addition, a significantly increased risk for MND was found in patients with previous histories of trauma, but confounding variables may account for this association.
Results of intensive prevalence surveys on multiple sclerosis carried out in different small regions of Italy have suggested that this country falls into the high-frequency zone for the disease. To verify this hypothesis by studying a large population, we conducted intensive incidence and prevalence survey in the province of Ferrara, northern Italy (mean population, 386,000). Based on 128 patients, the mean incidence per year for the period 1965 through 1979 was 2.2 cases per 100,000. On October 24, 1981, the prevalence rate was 46.1 cases per 100,000. The results support the view that northern Italy is a high-risk area for multiple sclerosis.
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