Patricia Brigatte

Publications (5)12.83 Total impact

• Article: Peripheral kappa and delta opioid receptors are involved in the antinociceptive effect of crotalphine in a rat model of cancer pain.

  Patricia Brigatte, Katsuhiro Konno, Vanessa Pacciari Gutierrez, Sandra Coccuzzo Sampaio, Vanessa Olzon Zambelli, Gisele Picolo, Rui Curi, Yara Cury
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  ABSTRACT: Cancer pain is an important clinical problem and may not respond satisfactorily to the current analgesic therapy. We have characterized a novel and potent analgesic peptide, crotalphine, from the venom of the South American rattlesnake Crotalus durissus terrificus. In the present work, the antinociceptive effect of crotalphine was evaluated in a rat model of cancer pain induced by intraplantar injection of Walker 256 carcinoma cells. Intraplantar injection of tumor cells caused the development of hyperalgesia and allodynia, detected on day 5 after tumor cell inoculation. Crotalphine (6μg/kg), administered p.o., blocked both phenomena. The antinociceptive effect was detected 1h after treatment and lasted for up to 48hours. Intraplantar injection of nor-binaltorphimine (50g/paw), a selective antagonist of κ-opioid receptors, antagonized the antinociceptive effect of the peptide, whereas N,N-diallyl-Tyr-Aib-Phe-Leu (ICI 174,864, 10μg/paw), a selective antagonist of δ-opioid receptors, partially reversed this effect. On the other hand, D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr amide (CTOP, 20g/paw), an antagonist of μ-opioid receptors, did not modify crotalphine-induced antinociception. These data indicate that crotalphine induces a potent and long lasting opioid-mediated antinociception in cancer pain.
  Pharmacology Biochemistry and Behavior 04/2013; · 2.53 Impact Factor
• Source

  Available from: Yara Cury

  Dataset: crotalphine and neuropathic pain

  Marucia Chacur, Gisele Picolo, Sandra Coccuzzo Sampaio, Patricia Brigatte, Yara Cury, Vanessa Pacciari Gutierrez, Katsuhiro Konno, Vanessa Olzon Zambelli
• Article: The peripheral L-arginine-nitric oxide-cyclic GMP pathway and ATP-sensitive K⁺ channels are involved in the antinociceptive effect of crotalphine on neuropathic pain in rats.

  Vanessa P Gutierrez, Vanessa O Zambelli, Gisele Picolo, Marucia Chacur, Sandra C Sampaio, Patricia Brigatte, Katsuhiro Konno, Yara Cury
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  ABSTRACT: Crotalphine, a 14 amino acid peptide first isolated from the venom of the South American rattlesnake Crotalus durissus terrificus, induces a peripheral long-lasting and opioid receptor-mediated antinociceptive effect in a rat model of neuropathic pain induced by chronic constriction of the sciatic nerve. In the present study, we further characterized the molecular mechanisms involved in this effect, determining the type of opioid receptor responsible for this effect and the involvement of the nitric oxide-cyclic GMP pathway and of K⁺ channels. Crotalphine (0.2 or 5 μg/kg, orally; 0.0006 μg/paw), administered on day 14 after nerve constriction, inhibited mechanical hyperalgesia and low-threshold mechanical allodynia. The effect of the peptide was antagonized by intraplantar administration of naltrindole, an antagonist of δ-opioid receptors, and partially reversed by norbinaltorphimine, an antagonist of κ-opioid receptors. The effect of crotalphine was also blocked by 7-nitroindazole, an inhibitor of the neuronal nitric oxide synthase; by 1H-(1,2,4) oxadiazolo[4,3-a]quinoxaline-1-one, an inhibitor of guanylate cyclase activation; and by glibenclamide, an ATP-sensitive K⁺ channel blocker. The results suggest that peripheral δ-opioid and κ-opioid receptors, the nitric oxide-cyclic GMP pathway, and ATP-sensitive K⁺ channels are involved in the antinociceptive effect of crotalphine. The present data point to the therapeutic potential of this peptide for the treatment of chronic neuropathic pain.
  Behavioural pharmacology 11/2011; 23(1):14-24. · 2.85 Impact Factor
• Article: Crotalphine induces potent antinociception in neuropathic pain by acting at peripheral opioid receptors.

  Vanessa Pacciari Gutierrez, Katsuhiro Konno, Marucia Chacur, Sandra Coccuzzo Sampaio, Gisele Picolo, Patricia Brigatte, Vanessa Olzon Zambelli, Yara Cury
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  ABSTRACT: Neuropathic pain is an important clinical problem and it is usually resistant to the current therapy. We have recently characterized a novel analgesic peptide, crotalphine, from the venom of the South American rattlesnake Crotalus durissus terrificus. In the present work, the antinociceptive effect of crotalphine was evaluated in an experimental model of neuropathic pain induced in rats by chronic constriction of sciatic nerve. The effect of the peptide was compared to that induced by the crude venom, which confirmed that crotalphine is responsible for the antinociceptive effect of the crotalid venom on neuropathic pain. For characterization of neuropathic pain, the presence of hyperalgesia, allodynia and spontaneous pain was assessed at different times after nerve constriction. These phenomena were detected 24 h after surgery and persisted at least for 14 days. The pharmacological treatments were performed on day 14 after surgery. Crotalphine (0.2-5 microg/kg) and the crude venom (400-1600 microg/kg) administered p.o. inhibited hyperalgesia, allodynia and spontaneous pain induced by nerve constriction. The antinociceptive effect of the peptide and crude venom was long lasting, since it was detected up to 3 days after treatment. Intraplantar injection of naloxone (1 microg/paw) blocked the antinociceptive effect, indicating the involvement of opioid receptors in this phenomenon. Gabapentin (200 mg/kg, p.o.), and morphine (5 mg/kg, s.c.), used as positive controls, blocked hyperalgesia and partially inhibited allodynia induced by nerve constriction. These data indicate that crotalphine induces a potent and long lasting opioid antinociceptive effect in neuropathic pain that surpasses that observed with standard analgesic drugs.
  European Journal of Pharmacology 11/2008; 594(1-3):84-92. · 2.52 Impact Factor
• Article: Walker 256 tumor-bearing rats as a model to study cancer pain.

  Patricia Brigatte, Sandra Coccuzzo Sampaio, Vanessa Pacciari Gutierrez, José Luiz Guerra, Idércio Luiz Sinhorini, Rui Curi, Yara Cury
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  ABSTRACT: An animal model of cancer pain induced by injection of Walker 256 carcinoma cells into the plantar surface of rat hind paw is described. Tumor growth and the occurrence of metastasis were investigated by histopathological analysis. Tumor cell growth was also analyzed plethysmographically by the increase in paw volume. For characterization of pain symptoms, hyperalgesia, allodynia, and spontaneous pain were evaluated 5 to 8 days after cell injection. The volume of the inoculated paw started to increase on day 2 after inoculation, being 40% higher on day 5 after injection. At this time, there was a marked proliferation of tumor cells, with the presence of anaplastic and pleomorphic cells, nucleoli, and atypical mitotic features. On days 7 and 8 after injection, histopathological analysis of popliteal lymph nodes showed the presence of tumor cells. The intraplantar injection of Walker 256 cells caused hyperalgesia at day 5 after cell inoculation. Low-threshold mechanical allodynia was significant 2 days after cell injection, being increased on day 5. In addition, inoculation of tumor cells induced gross behavior, characterized by a significant increase in licking and lifting of the injected paw 5 days after injection. The pain-enhancing effect caused by cell inoculation was partially inhibited by indomethacin on day 2 after cell injection, whereas morphine blocked allodynia on days 2 and 5. These results indicate that intraplantar injection of Walker 256 cells cause pain symptoms characteristic of cancer pain. This experimental model can then be used to investigate new analgesic or anti-tumor drugs. PERSPECTIVE: This article presents a new animal model for studying cancer pain and metastasis. This model could help in understanding the mechanisms involved in cancer pain symptoms and may be used for the investigation of new analgesic or anti-tumor drugs.
  Journal of Pain 06/2007; 8(5):412-21. · 4.93 Impact Factor