Analgesic Effect of Crotalphine in a New Model of Rat Bone Cancer Pain

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dc.contributor Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.author CURY, Yara
GUTIERREZ, Vanessa P.
BRIGATTE, Patricia
ZAMBELLI, Vanessa O.
PICOLO, Gisele
CARVALHO, Juliana S. de
MARQUES, Fabio FMUSP-HC
dc.date.issued 2012
dc.identifier.citation TOXICON, v.60, n.2, Special Issue, p.168-169, 2012
dc.identifier.issn 0041-0101
dc.identifier.uri http://observatorio.fm.usp.br/handle/OPI/3191
dc.description.abstract Background: Crotalphine (CRP), a peptide first identified and isolated from the South American rattlesnake Crotalus durissus terrificus venom, induces analgesic effect mediated by opioid receptors. The aim of this work is to characterize the analgesic effect of crotalphine in a new model of bone cancer pain induced by inoculation of Walker 256 tumor cells into the rat femoral cavity. Methods: Bone tumor implantation and metastasis were determined by histopathological analysis. Bone metabolic alterations were determined by scintigraphy, using 99mTc-MDP. Femoral images were obtained before and 7, 14 and 21 days after tumor cell injection. Bone cancer pain was characterized by the presence of hyperalgesia (rat paw pressure test) and allodynia (von Frey filaments). Results and Discussion: Photomicrographs analyzed 21 days after injection of tumor cells, demonstrated the presence of tumor cells in the femur of the animals. Incorporation of 99mTc-MDP was significant 7, 14 and 21 days, suggesting the development of tumor on the femoral cavity. Histopathological analysis demonstrated the presence of tumor cells in the lung and spleen, but not in the liver and kidneys of the rats. The results indicate that cells inoculated into femoral bone marrow can spread to some organs, including lymphoid organs. Hyperalgesia and allodynia were detected on days 1, 3, 7, 14 and 21 after cell inoculation. Interestingly, the paw withdrawal threshold in the von Frey test was reduced not only in the ipsilateral hind paw but also in the contralateral one, demonstrating the existence of bilateral allodynia (mirror-image pain). To evaluate the involvement of prostanoids in these nociceptive phenomena, Indomethacin, a cyclooxygenase inhibitor, was administered 3,7,14 and 21 days after tumor cell injection. Indomethacin only partially inhibited hyperalgesia and allodynia induced by bone cancer, indicating the involvement of prostanoids in bone cancer pain. The contribution of prostanoids is more significant within the first 3 days after cell injection. CRP (8μg/kg) administered on day 21, blocked hyperalgesia, allodynia and mirror image pain. The analgesic effect was detected up to 2 days after peptide administration and was blocked by κ-opioid receptor antagonist and partially inhibited by δ-opioid antagonists, indicating the involvement of opioid receptors. Morphine only partially inhibited allodynia and hyperalgesia. Conclusions: Results indicate that injection of tumor cells causes bone cancer and pain. CRP induces a potent and long-lasting antinociception in this model, with higher efficacy as compared to standard analgesic drugs.
dc.description.sponsorship · Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
· Centros de Pesquisa, Inovação e Difusão (CEPID)
· Instituto Nacional de Ciência e Tecnologia em Toxinas (INCTTOX)
dc.language.iso eng
dc.publisher PERGAMON-ELSEVIER SCIENCE LTD
dc.relation.ispartof Toxicon
dc.rights restrictedAccess
dc.subject crotalphine; analgesia; bone cancer pain
dc.title Analgesic Effect of Crotalphine in a New Model of Rat Bone Cancer Pain
dc.type conferenceObject
dc.rights.holder Copyright PERGAMON-ELSEVIER SCIENCE LTD
dc.description.conferencedate JUL 08-13, 2012
dc.description.conferencelocal Honolulu - HI, EUA
dc.description.conferencename 17th World Congress of the International-Society-on-Toxinology (IST)/Venom Week/4th International Scientific Symposium on All Things Venomous
dc.description.group LIM/43
dc.identifier.doi 10.1016/j.toxicon.2012.04.145
dc.type.category meeting abstract
dc.type.version publishedVersion
hcfmusp.author MARQUES, Fabio:HC:LIM/43
hcfmusp.author.external · CURY, Yara:Inst Butantan, Lab Especial Dor & Sinalizacao, Sao Paulo, Brazil
· GUTIERREZ, Vanessa P.:Inst Butantan, Lab Especial Dor & Sinalizacao, Sao Paulo, Brazil
· BRIGATTE, Patricia:Univ Estadual Sao Paulo UNESP, Rio Claro, Brazil
· ZAMBELLI, Vanessa O.:Inst Butantan, Lab Especial Dor & Sinalizacao, Sao Paulo, Brazil
· PICOLO, Gisele:Inst Butantan, Lab Especial Dor & Sinalizacao, Sao Paulo, Brazil
· CARVALHO, Juliana S. de:Inst Butantan, Lab Especial Dor & Sinalizacao, Sao Paulo, Brazil
hcfmusp.origem.id WOS:000305721800146
hcfmusp.publisher.city OXFORD
hcfmusp.publisher.country ENGLAND
dc.description.index MEDLINE
hcfmusp.citation.wos 0
hcfmusp.affiliation.country Brasil


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