Inhibition by neuropeptides of interleukin-1 beta-induced, prostaglandin-independent hyperalgesia.

The cytokine interleukin-1 beta (IL-1 beta) is a potent hyperalgesic agent in the rat whereas IL-1 alpha is relatively inactive (Ferreira et al., 1988). IL-1 beta induced a dose-dependent increase in the sensitivity of rat paws to mechanical stimulation following intra-plantar injection but this effect was not reduced by indomethacin (1.0 mg kg-1, p.o.), at a dose known to inhibit completely prostaglandin synthesis in the rat (Salmon et al., 1983). Prostaglandin (PG)E2 enhanced sensitivity to both mechanical pressure and increased temperature but IL-1 beta enhanced only sensitivity to pressure. These observations indicate that IL-1 beta sensitized pressure-sensitive but not temperature-sensitive sensory neurones, through a prostaglandin-independent mechanism. Hyperalgesia induced by IL-1 beta but not PGE2, was inhibited by the neuropeptide melanocyte-stimulating hormone (alpha MSH) and its analogue [Nle4, D-Phe7] alpha MSH which are known to antagonize IL-1 responses in other systems (Holdeman & Lipton, 1985; Cannon et al., 1986). IL-1 beta-induced hyperalgesia was also reduced by the putative IL-1 beta antagonist Lys-D-Pro-Thr (Ferreira et al., 1988) but alpha MSH and its analogue were 10-50 times more potent.

Effect of neurokinin A, substance P and calcitonin gene related peptide in peripheral hyperalgesia in the rat paw.

The effect of neurokinin A (NKA), substance P (SP) and calcitonin gene-related peptide (CGRP) in peripheral hyperalgesia was studied in rats using a modification of the Randall-Selitto paw test. NKA was 10 times more potent than SP which was 500 times more potent than CGRP in inducing hyperalgesia in the rat paw, suggesting that NKA and SP but not CGRP could have an important role in acute hyperalgesic conditions. Furthermore, sensitization induced by several injections of subthreshold doses of NKA or CGRP suggest that these neuropeptides along with SP could participate as mediators or modulators of chronic pain.

Possible participation of endogenous opioid peptides on the mechanism involved in analgesia induced by vouacapan.

The involvement of opioid peptides in the mechanism of action of vouacapan, a new experimental compound extracted from seeds of Pterodon poligalaeflorus Benth, was investigated both in mice utilizing acetic acid writhing response and in rats utilizing inflammatory hyperalgesia induced by carrageenan and modified Randall-Selitto method. Vouacapan, in both models, caused a dose-dependent analgesia when injected p.o., s.c. and i.p. The analgesic effect was partially blocked by naloxone, nalorphine and n-methyl-nalorphine. Significant tolerance to analgesic effect was observed following repeated administration of vouacapan or morphine. On the last day of treatment, cross administration revealed symmetrical and asymmetrical cross-tolerance between vouacapan and morphine, in rats and mice, respectively. We conclude that a release of endorphins could be involved in the analgesic mechanism of vouacapan in both models tudied.

Evidence of the involvement of biogenic amines in the antinociceptive effect of a vouacapan extracted from Pterodon polygalaeflorus Benth.

In view of the extensive use of Pterodon species in Brazilian folk medicine, the present investigation was performed to examine the involvement of biogenic amines in antinociceptive by a vouacapan (6 alpha-7 beta-dihydroxy vouacapan-17 beta-oate), extracted from seeds of Pterodon polygalaeflorus Benth), using acetic acid writhing test in mice. The alpha 2-adrenergic (yohimbine) and D2-dopaminergic (domperidone) antagonists and the pretreatment with the peripheral noradrenergic depletor, guanethidine partially inhibited the antinociceptive effect of vouacapan. Dopamine and D2 dopaminergic agonist (Ly 17155) caused antinociceptive that was not antagonized by naloxone but by domperidone, whereas noradrenaline induce pain. A synergistic analgesic effect was obtained when vouacapan was associated with clonidine or dopamine. These results indicate that vouacapan acts, at least in part, through activation of the catecholaminergic system.