Comparative effect of Phoneutria nigriventer spider venom and capsaicin on the rat paw oedema

doi:10.1016/S0024-3205(01)01234-6

Life Sciences

Volume 69, Issue 13, 17 August 2001, Pages 1573-1585

https://doi.org/10.1016/S0024-3205(01)01234-6 Get rights and content

Abstract

Capsaicin, the pungent component of hot peppers, and the venom of the spider Phoneutria nigriventer are able to activate sensory nerves resulting in cutaneous neurogenic plasma extravasation. This study was undertaken to compare the ability of these substances to evoke oedema in the rat hind-paw and mechanisms underlying this effect. Subplantar injection of either Phoneutria nigriventer venom (PNV; 1–100 μg/paw) or capsaicin (10–200 μg/paw) caused a significant paw oedema that was potentiated by CGRP (10 pmol/paw). In rats treated neonatally with capsaicin to deplete neuropeptides, the paw oedema induced by either PNV (100 μg/paw) or capsaicin (100 μg/paw) was partially reduced (P<0.05). The tachykinin NK₁ receptor antagonist SR140333 (0.2 μmol/kg; i.v.) prevented the paw oedema induced by the tachykinin NK₁ receptor agonist GR73632 (30 pmol/paw) and partially reduced paw oedema induced by PNV or capsaicin. Treatment of rats with compound 48/80 (5 mg/kg; s.c. 3 days) or with both H₁ receptor antagonist (mepyramine; 1 nmol/paw) and 5-HT receptor antagonist (methysergide; 1 nmol/paw) significantly inhibited PNV- or capsaicin-induced paw oedema. The combined treatment with mepyramine and methysergide and SR140333 further reduced PNV- and capsaicin-induced paw oedema. The bradykinin B₂ receptor antagonist Hoe 140 affected neither PNV- nor capsaicin-induced responses. Our results suggest that PNV and capsaicin each induce paw oedema that is partially mediated by activation of sensory fibers culminating in the release of substance P as well as by activation of mast cells which in turn release amines such as histamine and 5-HT.

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Cited by (26)

Potamotrygon motoro stingray venom induces both neurogenic and inflammatory pain behavior in rodents
2018, Toxicon
Citation Excerpt :
ω-conotoxin MVIIC was purchased from Peninsula Laboratories International, USA. To investigate some of the possible pathways that PmV induces hyperalgesia, groups of rats were treated with: Guanethidine (depletor of peripheral sympathomimetic amines, 30 mg/kg, s.c., for 3 consecutive days before PmV injection) (Chacur et al., 2002), GR82334 (NK1 receptor antagonist, 1.4 μg/paw, i.pl., 15 min before PmV injection), GR94800 (NK2 receptor antagonist, 0.9 μg/paw, i.pl., 15 min before PmV injection) (Zanchet and Cury, 2003), capsazepine (vanilloid receptor antagonist), 30 μg/paw, i.pl., 15 min before PmV injection) (Costa et al., 2001), CGRP8-37 (CGRP receptor antagonist, 15 μg/paw, i.pl., 10 min before PmV injection) (Yu et al., 1998), verapamil (calcium channel type Cav1 blocker, 50 μg/paw, i.pl., 30 min before PmV injection), or ω-conotoxin MVIIC (selective calcium channel type Cav2.1 blocker, 20 μg/kg, i.p., 30 min before PmV injection) (Prado, 2001). Sterile saline was used as negative control for these pharmacological treatments and PmV injection.
Freshwater stingray accidents cause an immediate, intense, and unrelieved pain which is followed by edema, erythema and necrosis formation. Treatment for stingray envenomation is based on administration of analgesic, antipyretic and anti-inflammatory drugs. Concerning pain control, it is prescribed to immerse punctured limb on hot water to alleviate pain. There are no studies demonstrating specific targets on which stingray venom acts to promote pain. Therefore, the aim of this work was to investigate some mechanisms of Potamotrygon motoro venom (PmV) that contribute to nociception induction. Evaluating spontaneous pain behavior in mice injected i.pl. with PmV, it was seen that PmV induced both neurogenic and inflammatory pain. PmV also induced hyperalgesia in both mice and rats, evaluated through electronic von Frey and rat paw pressure test, respectively. Partial inhibition of hyperalgesia was observed in mice treated with cromolyn or promethazine, which indicated that mast cell and histamine via H1 receptor participate in the inflammatory pain. To search for some targets involved in PmVinduced hyperalgesia, the participation of TRPV1, calcium channels, neurokinins, CGRP, and norepinephrine, was evaluated in rats. It was seen that PmV-induced hyperalgesia occurs with the participation of neurokinins, mainly via NK1 receptor, CGRP, and calcium influx, through both P/Q and L-type voltage-dependent calcium channels, besides TRPV1 activation. The data presented herein indicate that PmV causes hyperalgesia in rodents which is dependent on the participation of several neuroinflammatory mediators.
Venomic and pharmacological activity of Acanthoscurria paulensis (Theraphosidae) spider venom
2013, Toxicon
Citation Excerpt :
In fact, 20 μg venom/paw was able to induce hind-paw edema after 10 min of administration. Phoneutria nigriventer (Costa et al., 2001; Zanchet and Cury, 2003) and Loxosceles gaucho (Barbaro et al., 2010) venoms and peptides isolated from Scaptocosa raptoria venom (Ferreira et al., 1998) also produced edema in rodents. These studies showed that pain and swelling caused by these spider venoms are related, as they involve the same molecular cascades.
In the present study we conducted proteomic and pharmacological characterizations of the venom extracted from the Brazilian tarantula Acanthoscurria paulensis, and evaluated the cardiotoxicity of its two main fractions. The molecular masses of the venom components were identified by mass spectrometry (MALDI-TOF-MS) after chromatographic separation (HPLC). The lethal dose (LD₅₀) was determined in mice. Nociceptive behavior was evaluated by intradermal injection in mice and the edematogenic activity by the rat hind-paw assay. Cardiotoxic activity was evaluated on in situ frog heart and on isolated frog ventricle strip. From 60 chromatographic fractions, 97 distinct components were identified, with molecular masses between 601.4 and 21,932.3 Da. A trimodal molecular mass distribution was observed: 30% of the components within 500-1999 Da, 38% within 3500–5999 Da and 21% within 6500–7999 Da. The LD₅₀ in mice was 25.4 ± 2.4 μg/g and the effects observed were hypoactivity, anuria, constipation, dyspnea and prostration until death, which occurred at higher doses. Despite presenting a dose-dependent edematogenic activity in the rat hind-paw assay, the venom had no nociceptive activity in mice. Additionally, the venom induced a rapid blockage of electrical activity and subsequent diastolic arrest on in situ frog heart preparation, which was inhibited by pretreatment with atropine. In the electrically driven frog ventricle strip, the whole venom and its low molecular mass fraction, but not the proteic one, induced a negative inotropic effect that was also inhibited by atropine. These results suggest that despite low toxicity, A. paulensis venom can induce severe physiological disturbances in mice.
Synthesis and pharmacological characterization of a novel nitric oxide-releasing diclofenac derivative containing a benzofuroxan moiety
2010, European Journal of Medicinal Chemistry
Citation Excerpt :
The results are expressed as the increase in paw volume (mL) calculated by subtracting the basal volume. The area under the time-course curve (AUC0–2h) was also calculated using the trapezoidal rule and the results expressed as total edema volume (mL h) by comparison with the vehicle rats [23]. The animals were orally treated with vehicle (1 mL of DMSO) or the anti-inflammatory compounds.
1-Oxy-benzo[1,2,5]oxadiazol-5-ylmethyl [2-(2,6-dichloro-phenylamino)-phenyl]-acetate, a new diclofenac derivative bearing a benzofuroxan heterocyclic moiety in its structure, was prepared by the reaction of sodium diclofenac and 5-bromomethyl-benzo[1,2,5]oxadiazole 1-oxide. Pharmacological characterization of this modified diclofenac maintained the anti-inflammatory activity similar to its parent compound assayed in vitro and in vivo. The ulcerogenic properties of native diclofenac were not observed with this modified compound, despite the inhibition of prostaglandin E₂ gastric content. The better gastric tolerability seems to be related to nitric oxide release ability.
Role of sensory innervation in the rat pulmonary neutrophil recruitment induced by staphylococcal enterotoxins type A and B
2009, European Journal of Pharmacology
Rat airways exposure to Staphylococcal enterotoxin A (SEA) and B (SEB) induces marked neutrophil influx. Since sensory neuropeptides play important roles in cell infiltration, in this study we have investigated its contribution in triggering SEA- and SEB-induced pulmonary neutrophil infiltration. Male Wistar rats were exposed intratracheally with SEA (3 ng/trachea) or SEB (250 ng/trachea). Animals received different in vivo pretreatments, after which the neutrophil counts and levels of substance P and IL-1 in bronchoalveolar lavage fluid were evaluated. Alveolar macrophages and peritoneal mast cells were incubated with SEA and SEB to determine the IL-1 and TNF-α levels. Capsaicin pretreatment significantly reduced SEA- and SEB-induced neutrophil influx in bronchoalveolar lavage fluid, but this treatment was more effective to reduce SEA responses. Treatments with SR140333 (tachykinin NK₁ receptor antagonist) and SR48968 (tachykinin NK₂ receptor antagonist) decreased SEA-induced neutrophil influx, whereas SEB-induced responses were inhibited by SR140333 only. Cyproheptadine (histamine/5-hydroxytriptamine receptor antagonist) and MD 7222 (5-HT₃ receptor antagonist) reduced SEA- and SEB-induced neutrophil influx. The substance P and IL-1 levels in bronchoalveolar lavage fluid of SEA-exposed rats were significantly higher than SEB. In addition, SEA (but not SEB) significantly released mast cell TNF-α. Increased production of TNF-α and IL-1 in alveolar macrophages was observed in response to SEA and SEB. In conclusion, sensory neuropeptides contribute significantly to SEA- and SEB-induced pulmonary neutrophil recruitment, but SEA requires in a higher extent the airways sensory innervation, and participation of mast cells and alveolar macrophage products.
Inflammatory events induced by brown spider venom and its recombinant dermonecrotic toxin: A pharmacological investigation
2009, Comparative Biochemistry and Physiology - C Toxicology and Pharmacology
Accidents involving Brown spider (Loxosceles sp.) venom produce a massive inflammatory response in injured region. This venom has a complex mixture of different toxins, and the dermonecrotic toxin is the major contributor to toxic effects. The ability of Loxosceles intermedia venom and a recombinant isoform of dermonecrotic toxin to induce edema and increase in vascular permeability was investigated. These toxins were injected into hind paws and caused a marked dose and time-dependent edema and increase in vascular permeability in mice. Furthermore, the enzymatic activity of venom toxins may be primal for these effects. A mutated recombinant isoform of dermonecrotic toxin, that has only residual enzymatic activity, was not able to induce these inflammatory events. Besides the previous heating of toxins markedly reduced the paw edema and vascular permeability showing that thermolabile constituents can trigger these effects. In addition, the ability of these venom toxins to evoke inflammatory events was partially reduced in compound 48/80-pretreated animals, suggesting that mast cells may be involved in these responses. Pretreating mice with histamine (prometazine and cetirizine) and serotonin (methysergide) receptor antagonists significantly attenuated toxins induced edema and vascular permeability. Moreover, HPLC analysis of whole venom showed the presence of histamine sufficient to induce inflammatory responses. In conclusion, these inflammatory events may result from the activation of mast cells, which in turn release bioamines and may be related to intrinsic histamine content of venom.
Mechanisms involved in the rat peritoneal leukocyte migration induced by a Kunitz-type inhibitor isolated from Dimorphandra mollis seeds
2009, Toxicon
Citation Excerpt :
The following drugs were used at the indicated doses and schedules of administration: (1) Dexamethasone (0.5 mg/kg) was administered s.c. 1 h before DMTI-II injection; (2) the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib (3 mg/kg) was administered s.c. 1 h before DMTI-II administration (Filliatre et al., 2001); (3) the lypoxygenase inhibitor AA861 (0.2 mg/kg) was administered i.v. 15 min before DMTI-II injection (Filliatre et al., 2001); (4) platelet-activating factor (PAF) antagonist receptor PCA4248 (5 mg/kg) was administered i.v. 1 h before DMTI-II injection (Filliatre et al., 2001); (5) the tachykinin NK1 receptor antagonist ((S)1-{2-[3-(3,4-dichlorophenyl)-1-(3-isopropoxyphenylacetyl)piperidim-3-yl]ethyl}-4-phenyl-1-azibuabicyclo[2.2.2.] octane chloride) SR-140333 (100 μg/kg) was administered i.v. immediately before the intraperitoneal injection of DMTI-II (Costa et al., 2001); (6) the tachykinin NK2 receptor antagonist ((S)-N-methyl-N[4-(4-acetylamino-4-phenylpiperridino)-2-(3,4,-dichlorophenyl)butyl]benzamide) SR48968 (1 mg/kg) was administered immediately before DMTI-II injection (Inoue et al., 1997); (7) the non-selective nitric oxide (NO) synthesis inhibitor Nω-nitro-l-arginine methyl ester (l-NAME; 20 mg/kg) was administered i.v. immediately before DMTI-II injection (Franco-Penteado et al., 2001); (8) the inducible NO synthase inhibitor aminoguanidine (75 mg/kg) was administered i.v. immediately before DMTI-II injection (Franco-Penteado et al., 2001). The cellular migration was evaluated 16 h-post-DMTI-II administration.
DMTI-II is a Kunitz-type inhibitor isolated from Dimorphandra mollis seeds that causes rat inflammatory edema by mechanisms involving activation of mast cells and sensory C-fibers. The present study aimed to further explore the inflammatory mechanisms involved in DMTI-II-induced inflammation, focusing to the leukocyte migration in vivo. Male Wistar rats (250–280 g) were injected with DMTI-II (1–100 μg/cavity), and at 4–24 h thereafter the leukocyte counts in peritoneal lavage were evaluated. DMTI-II caused dose- and time-dependent accumulation of neutrophils and eosinophils. The peritoneal neutrophil influx initiated at 4 h, achieving maximal responses at 16 h after DMTI-II injection (16- and 22-fold increase, respectively). The DMTI-II-induced eosinophil recruitment was observed as early as 4 h achieving the maximal responses at 16 h (12- and 17-fold increase, respectively). The mononuclear cell number increased at 4 h and 16 h (1.5-fold and 1.6-increase, respectively). Prior treatments with dexamethasone, the cyclooxygenase (COX) inhibitors indomethacin and celecoxib, as well as the PAF receptor antagonist PCA4248 largely reduced the neutrophil and eosinophil accumulation. The selective lypoxygenase inhibitor AA861, the tachykinin NK₁ antagonist SR-140333 and the nitric oxide inhibitor L-NAME reduced only the eosinophil number. The eotaxin levels were significantly higher in DMTI-II-injected rats compared with control animals. In conclusion, DMTI-II causes an early migration of eosinophils and neutrophils by mechanisms involving COX-2- and lipoxygenase-derived metabolites, PAF, substance P and NO. The capacity of DMTI-II to recruit eosinophils at early times is likely to reflect the allergen properties of proteinase inhibitors belonging to Kunitz family.

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Original articlesComparative effect of Phoneutria nigriventer spider venom and capsaicin on the rat paw oedema

Abstract

Original articles
Comparative effect of Phoneutria nigriventer spider venom and capsaicin on the rat paw oedema