Participation of Central Muscarinic Receptors on the Nervous Form of Chagas Disease in Mice Infected via Intracerebroventricular with Colombian Trypanosoma cruzi Strain

Acute chagasic encephalitis is a clinically severe central nervous system (CNS) manifestation. However, the knowledge of the nervous form of Chagas disease is incomplete. The role of the muscarinic acetylcholine receptor (mAChR) on mice behavior and brain lesions induced by Trypanosoma cruzi (Colombian strain) was herein investigated in mice treated with the mAChR agonist and antagonist (carbachol and atropine), respectively. Immunosuppressed or non-immunosuppressed mice were intracerebroventricularly (icv) or intraperitoneally (ip) infected. All groups were evaluated 15 d.p.i. (days post infection). Intraperitoneally infected animals had subpatent parasitemia. Patent parasitemia occurred only in icv infected mice. The blockade of mAChR increased the parasitemia, parasitism and lesions compared to its activation. Infected not treated (INT ip) mice did not present meningitis and encephalitis, regardless of immunosuppression. INT icv brains presented higher cellularity, discrete signs of cellular degeneration, frequent presence of parasites and focal meningitis. The immunosuppressed atropine + icv mice presented increased intracellular parasitism associated with degenerative parenchymal changes, while carbachol + icv mice presented discrete meningitis, preservation of the cortex and absence of relevant parasitism. Cholinergic receptor blockage increased impairment of coordination vs. receptor activation. Muscarinic cholinergic pathway seems to be involved in immune mediated cell invasion events while its blockade favored infection evolution, brain lesions, and behavioral alterations.

Topical Antinociceptive Effect ofVanillosmopsis arboreaBaker on Acute Corneal Pain in Mice

This study aimed to assess the possible topical antinociceptive activity ofVanillosmopsis arboreaBaker essential oil (EOVA) and to clarify the underlying mechanism, using the acute model of chemical (eye wiping) nociception in mice. EOVA (25 to 200 mg/kg; p.o. and topical) evidenced significant antinociception against chemogenic pain in the test model of formalin-induced neuroinflammatory pain. Local application of 5 M NaCl solution on the corneal surface of the eye produced a significant nociceptive behavior, characterized by eye wiping. The number of eye wipes was counted during the first 30 s. EOVA (25, 50, 100, and 200 mg/kg; p.o. and topical) significantly decreased the number of eye wipes. Naloxone, yohimbine, L-NAME, theophylline, glibenclamide, and ruthenium red had no effect on the antinociceptive effect of EOVA. However, ondansetron, p-chlorophenylalanine methyl ester (PCPA), capsazepine, prazosin, and atropine prevented the antinociception induced by EOVA. These results indicate the topical antinociceptive effect of EOVA and showed that 5-HT,α1, TRPV1, and central muscarinic receptors might be involved in the antinociceptive effect of EOVA in the acute corneal model of pain in mice.

Central Muscarinic Receptors Signal Pilocarpine-induced Salivation

Although cholinergic agonists such as pilocarpine injected peripherally can act directly on salivary glands to induce salivation, it is possible that their action in the brain may contribute to salivation. To investigate if the action in the brain is important to salivation, we injected pilocarpine intraperitoneally after blockade of central cholinergic receptors with atropine methyl bromide (atropine-mb). In male Holtzman rats with stainless steel cannulas implanted into the lateral ventricle and anesthetized with ketamine, atropine-mb (8 and 16 nmol) intracerebroventricularly reduced the salivation induced by pilocarpine (4 μmol/kg) intraperitoneally (133 + 42 and 108 + 22 mg/7 min, respectively, vs. saline, 463 + 26 mg/7 min), but did not modify peripheral cardiovascular responses to intravenous acetylcholine. Similar doses of atropine-mb intraperitoneally also reduced pilocarpine-induced salivation. Therefore, systemically injected pilocarpine also enters the brain and acts on central muscarinic receptors, activating autonomic efferent fibers to induce salivation.