Participação dos sistemas opioidérgico e canabi-noidérgico na modulação endógena periférica da dor inflamatória muscular

Abstract

Pain processing starts from a noxious stimulus able to sensitize nociceptor peripheral terminals. Pain information converges from the periphery to the dorsal horn of the spi-nal cord through fibers type A, A and C. Once the information reaches the bone mar-row, a series of neuronal components modulates its transmission into the cortex, where it is then processed. Nevertheless, some systems, such as the opioid and the canabi-noidergic, are able to modulate the rise of the nociceptive stimulus still in the periphery. Literature shows that during inflammatory muscle pain, a number of mediators is re-leased, which is associated with the increased analgesic activity mediated by these sys-tems. Little is known, however, about the influence of the latter on muscle pain. Ac-cordingly, our objective was to verify the participation of opioid and canabinoidergic systems in peripheral endogenous modulation of inflammatory muscle pain. To achieve the aimed purpose, male Wistar rats weighing between 180 and 220g were employed. Intramuscular (i.m.) injection of carrageenan (Cg) was used to induce inflammatory muscle pain, whereas the Randall & Sellito test, standardized for the tibialis anterior muscle (m.TA), was applied to verify the analgesic or hyperalgesic effect of the used drugs. Furthermore, we evaluated the opioid and cannabinoid receptors in the dorsal root ganglion (DRG) by the Western blot technique. According to the research data, for all tested doses the peak of the hyperalgesic effect of Cg was the third hour after its i.m. injection. The lesser effect occurred after the injection of a 100 l/ muscle dose, and the greatest effect at the 1.000 g Cg dose. Naloxone (50 and 25 l/ muscle), a non-selective antagonist for opioid receptors, as well as clocimanox (10 and 1 l/ muscle) and nor-binaltorphimine (100 and 50 l/ muscle), selective antagonists for the and opioid receptors, intensified the hyperlgesic effect of Cg (100 l/ muscle). The bio-molecular assay showed that the amount of these receptors has not been changed in DRG. On the other hand, the opioid receptor antagonist, naltrindole, was not able to intensify the hyperalgesia caused by Cg. Furthermore, bestatin (800, 400 and 200 l/ muscle), an aminopeptidase enzyme inhibitor, which degrades opioid peptides, reversed the hyperalgesic effect of Cg in its highest dose (1000 l/ muscle). When the canna-binoid type 1 receptor (CB1) was antagonized with the use of AM251 (320 and 160 l/ muscle), the hyperalgesic effect of Cg (100 l/ muscle) was intensified. The same effect was not observed with the use of cannabinoid receptor antagonist of type 2, AM630 (400 l/ muscle). The quantified levels of CB1 expressed in DRG are not altered, whereas inhibitors of enzymes that degrade anandamide (AEA) and 2-Arachidonoylglycerol (2-AG), MAFF (16, 8 and 4 l/ muscle) and JZL (60 and 30 l/ muscle), respectively, as well as the the uptake blocker VDM11 (80, 40 and 20 l/ mus-cle), reversed the hyperalgesic effect of Cg in the highest dose (1000 l/ muscle). Therefore, results indicate that the muscular hyperalgesia induced by Cg undergoes a certain modulation already at the peripheral level. This modulation would have occured selectively as regards the opioid and cannabinoid receptors, without increasing the lev-els of the latter in the DRG. Thus, we believe that this modulation takes place at the muscle level by increasing the supply of endogenous opioids and cannabinoid peptides, as well as through a possible increase in the activation of these receptors during the hy-peralgesic development.