Neuropeptide Y concentrations in experimental Leishmania major cutaneous leishmaniasis

Ahmed, Ahmed Abdelaziz; Ahmed, Mahmood; Theodorsson, Elvar; Nordlind, Klas

doi:10.1097/00001756-199810050-00025

Cited by 6 publications

(7 citation statements)

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“…The nociceptive phenomenon in human CL induced by Leishmania major has been associated with inflammatory peripheral neural involvement (Kubba et al, 1987;Satti et al, 1989). Moreover, among the studies dealing with CL only, hyperalgesia has been investigated using classical models and BALB/c mice (Ahmed et al, 1998;Kanaan et al, 2000;Karam et al, 2006;Amaral et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

The endogenous cytokine profile and nerve fibre density in mouse ear Leishmania major-induced lesions related to nociceptive thresholds

Cangussú

Souza

Castro

et al. 2013

Experimental Parasitology

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Several reports have shown that cutaneous leishmaniasis lesions are painless, suggesting that Leishmania infection interferes with pain perception. Comparisons of inflammation-induced hyperalgesia between BALB/c and C57BL/6 mice have been little explored in the literature, and comparative data regarding nociception in leishmaniasis are non-existent. In susceptible BALB/c mice and resistant C57BL/6 mice that were intradermally inoculated with a low dose of Leishmania major in the ear, we investigated the variation in nociception over a 12-wk period post-infection and this variation's association with the structure of nerve fibres and the presence of endogenous cytokines that are classically considered hyper- or hypo-nociceptive. Infected BALB/c mice presented susceptibility and severe lesions. Infected C57BL/6 mice exhibited resistance and healing lesions. The immune response involved pro- and anti-inflammatory cytokine secretion, respectively. The infection-induced hypoalgesia in BALB/c mice after wks 9 was accompanied by decreased levels of IL-6 and IL-10 in ear tissue with intact nerves. C57BL/6 mice showed short-lived hyperalgesia in wks 2, which was related to increased local levels of IL-6, KC/CXCL-1, TNF-α and IL-10 and a decrease in nerve density. The increase in pro-inflammatory cytokine IL-6, KC/CXCL-1 and TNF-α levels during hyperalgesia suggested a role for these mediators in afferent nerve sensitisation, which was secondary to the inflammatory damage of nerve fibres stained by PGP 9.5. In contrast, the mechanisms of hypoalgesia may include the downregulation of cytokines, the preservation of the structure of nerve endings, and as yet uninvestigated unidentified differences in neurotransmitter release or a direct role of the parasites in the context of the progressive and permissive inflammatory response of BALB/c mice.

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Section: Introductionmentioning

confidence: 99%

The endogenous cytokine profile and nerve fibre density in mouse ear Leishmania major-induced lesions related to nociceptive thresholds

Cangussú

Souza

Castro

et al. 2013

Experimental Parasitology

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“…Leishmania models have been used to evaluate the intimate link between the parasite and its milieu, the sensory and autonomic neuropeptides, and macrophage function during parasite infection ( Ahmed et al., 1998a ; Ahmed et al., 1998b ; Ahmed et al., 1998c ; Ahmed et al., 2001 ).…”

Section: Gpcr Like Signaling Systems In Leishmaniamentioning

confidence: 99%

“…Moreover, both sensory (substance P, SP; calcitonin gene-related peptide, CGRP; and somatostatin, SOM), and autonomic (neuropeptide Y, NPY; and vasoactive intestinal peptide, VIP) neuropeptides, have been used in L. (L.) major -macrophage models to analyze macrophage function ( Ahmed et al., 1998a ; Ahmed et al, 1998b ; Ahmed et al., 2001 ). The results indicate that neuropeptides modulate the initial steps of host-parasite interaction and influence disease development by affecting promastigote-induced macrophage migration.…”

Section: Gpcr Like Signaling Systems In Leishmaniamentioning

confidence: 99%

G Protein-Coupled Receptors as Potential Intercellular Communication Mediators in Trypanosomatidae

Díaz

Febres

Giammarresi

et al. 2022

Front. Cell. Infect. Microbiol.

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Detection and transduction of environmental signals, constitute a prerequisite for successful parasite invasion; i.e., Leishmania transmission, survival, pathogenesis and disease manifestation and dissemination, with diverse molecules functioning as inter-cellular signaling ligands. Receptors [i.e., G protein-coupled receptors (GPCRs)] and their associated transduction mechanisms, well conserved through evolution, specialize in this function. However, canonical GPCR-related signal transduction systems have not been described in Leishmania, although orthologs, with reduced domains and function, have been identified in Trypanosomatidae. These inter-cellular communication means seem to be essential for multicellular and unicellular organism’s survival. GPCRs are flexible in their molecular architecture and may interact with the so-called receptor activity-modifying proteins (RAMPs), which modulate their function, changing GPCRs pharmacology, acting as chaperones and regulating signaling and/or trafficking in a receptor-dependent manner. In the skin, vasoactive- and neuro- peptides released in response to the noxious stimuli represented by the insect bite may trigger parasite physiological responses, for example, chemotaxis. For instance, in Leishmania (V.) braziliensis, sensory [Substance P, SP, chemoattractant] and autonomic [Vasoactive Intestinal Peptide, VIP, and Neuropeptide Y, NPY, chemorepellent] neuropeptides at physiological levels stimulate in vitro effects on parasite taxis. VIP and NPY chemotactic effects are impaired by their corresponding receptor antagonists, suggesting that the stimulated responses might be mediated by putative GPCRs (with essential conserved receptor domains); the effect of SP is blocked by [(D-Pro 2, D-Trp7,9]-Substance P (10-6 M)] suggesting that it might be mediated by neurokinin-1 transmembrane receptors. Additionally, vasoactive molecules like Calcitonin Gene-Related Peptide [CGRP] and Adrenomedullin [AM], exert a chemorepellent effect and increase the expression of a 24 kDa band recognized in western blot analysis by (human-)-RAMP-2 antibodies. In-silico search oriented towards GPCRs-like receptors and signaling cascades detected a RAMP-2-aligned sequence corresponding to Leishmania folylpolyglutamate synthase and a RAMP-3 aligned protein, a hypothetical Leishmania protein with yet unknown function, suggesting that in Leishmania, CGRP and AM activities may be modulated by RAMP- (-2) and (-3) homologs. The possible presence of proteins and molecules potentially involved in GPCRs cascades, i.e., RAMPs, signpost conservation of ancient signaling systems associated with responses, fundamental for cell survival, (i.e., taxis and migration) and may constitute an open field for description of pharmacophores against Leishmania parasites.

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“…Patients with cutaneous lesions report no pain according to most authors, while some report this sensation . Increasing experimental evidence in rodents with Leishmania major observed pain behaviour dependent on hyperalgesic cytokines production …”

Section: Introductionmentioning

confidence: 99%

Glucantime reduces mechanical hyperalgesia in cutaneous leishmaniasis and complete Freund's adjuvant models of chronic inflammatory pain

Silva

Mizokami

Fanti

et al. 2018

Journal of Pharmacy and Pharmacology

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Neuropeptide Y concentrations in experimental Leishmania major cutaneous leishmaniasis

Cited by 6 publications

References 1 publication

The endogenous cytokine profile and nerve fibre density in mouse ear Leishmania major-induced lesions related to nociceptive thresholds

The endogenous cytokine profile and nerve fibre density in mouse ear Leishmania major-induced lesions related to nociceptive thresholds

G Protein-Coupled Receptors as Potential Intercellular Communication Mediators in Trypanosomatidae

Glucantime reduces mechanical hyperalgesia in cutaneous leishmaniasis and complete Freund's adjuvant models of chronic inflammatory pain

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