Involvement of the glutamatergic system in the nociception induced intrathecally for a TRPA1 agonist in rats.

The transient receptor potential ankyrin 1 (TRPA1) is expressed in peripheral and spinal terminals of sensory neurons, jointly to the vanilloid receptor (TRPV1). A relevant peripheral role of TRPA1 receptor has been implicated in a variety of processes, including the detection of noxious cold, and diverse painful stimulus, but the functional role of TRPA1 receptor in nociceptive transmission at spinal cord in vivo is poorly known. Therefore, the aim of this study was to evaluate whether the glutamatergic system is involved in the transmission of nociceptive stimulus induced for a TRPA1 agonist in the rat spinal cord. We observed that cinnamaldehyde, a TRPA1 agonist, on spinal cord synaptosomes leads to an increase in [Ca(2+)](i) and a rapid release of glutamate, but was not able to change the specific [(3)H]-glutamate binding. In addition, spinally administered cinnamaldehyde produced heat hyperalgesia and mechanical allodynia in rats. This behavior was reduced by the co-injection (i.t.) of camphor (TRPA1 antagonist) or MK-801 (N-methyl-D-aspartate (NMDA) receptor antagonist) to cinnamaldehyde. Besides, the pretreatment with resiniferatoxin (RTX), a potent TRPV1 agonist, abolished the cinnamaldehyde-induced heat hyperalgesia. Here, we showed that intrathecal RTX results in a decrease in TRPA1 and TRPV1 immunoreactivity in dorsal root ganglion. Collectively, our results demonstrate the pertinent participation of spinal TRPA1 in the possible enhancement of glutamatergic transmission of nociceptive signals leading to increase of the hypersensitivity, here observed as heat hyperalgesia. Then the modulation of spinal TRPA1 might be a valuable target in painful conditions associated with central pain hypersensitivity.

Effect of leisure time and working activity on principal risk factors and relative interactions in active middle-aged men.

DESIGN: This study was designed to evaluate, in a cohort of 1039 middle-aged men, the interaction between the duration and intensity of physical activity performed either during leisure time (competitive sports, walking, cycling) or work, and principal coronary disease risk factors. METHOD: A cohort of subjects aged 45-64 years were recruited in 1993. Subjects included both individuals who were physically active and those who were sedentary, and were age-matched. RESULTS: Leisure time physical activity was inversely related to levels of total cholesterol, triglycerides, and fibrinogen, and to diastolic and systolic blood pressure. High-density lipoprotein cholesterol level was directly related to leisure time activity. Working activity, even if strenuous, was not related to risk profile. Leisure time activity did not favorably influence lipid levels in smokers, obese subjects or those with known dyslipidemia. CONCLUSIONS: This study further reinforces the use of continuous diet and drug treatment in dyslipidemic subjects and in smokers, who have to refrain from smoking if they are to benefit fully from the effects of physical activity.