S A Woller1, M Corr2, T L Yaksh1. 1. Department of Anesthesiology, University of California, San Diego, La Jolla, USA. 2. Division of Rheumatology, Allergy, and Immunology, University of California, San Diego, La Jolla, USA.
Abstract
BACKGROUND: Chemotherapeutic agents, such as cisplatin, are known to induce a persistent polyneuropathy. The mechanisms underlying the development of this pain are complex, and have only been investigated rodent models using male animals, despite an equivalent presentation of neuropathy between the sexes, clinically. METHODS: Male and female C57Bl/6, Tlr3(-/-) Tlr4(-/-) , Myd88(-/-) , Trif(lps2) and Myd88(-/-) /Trif(lps2) mice received 6 i.p. injections of cisplatin (2.3 mg/kg/day) every other day over the course of 2 weeks. Changes in tactile threshold were monitored during this time, continuing through day 23, using von Frey filaments. RESULTS: Male WT mice develop a persistent tactile allodynia resulting from cisplatin administration. Female mice develop an initial allodynia, but thresholds return to baseline by day 23. Deletion of TLR3, TLR4, MyD88 and Trif/MyD88 protects animals from the development of cisplatin-induced polyneuropathy, and there are no sex differences. Trif(lps2) male mice show a persistent tactile allodynia following cisplatin administration, while female mice show a reduced allodynia, and remain higher in threshold than their male counterparts. On day 18, animals were given the analgesic gabapentin, and thresholds were tested 45 min after. Gabapentin was effective in transiently reversing mechanical allodynia in those mice with lowered thresholds. CONCLUSIONS: It is important to continue examining both sexes in various pain models, as a mononeuropathy and polyneuropathy show sex differences in pain development and the role of TLR signalling.
BACKGROUND: Chemotherapeutic agents, such as cisplatin, are known to induce a persistent polyneuropathy. The mechanisms underlying the development of this pain are complex, and have only been investigated rodent models using male animals, despite an equivalent presentation of neuropathy between the sexes, clinically. METHODS: Male and female C57Bl/6, Tlr3(-/-) Tlr4(-/-) , Myd88(-/-) , Trif(lps2) and Myd88(-/-) /Trif(lps2) mice received 6 i.p. injections of cisplatin (2.3 mg/kg/day) every other day over the course of 2 weeks. Changes in tactile threshold were monitored during this time, continuing through day 23, using von Frey filaments. RESULTS: Male WT mice develop a persistent tactile allodynia resulting from cisplatin administration. Female mice develop an initial allodynia, but thresholds return to baseline by day 23. Deletion of TLR3, TLR4, MyD88 and Trif/MyD88 protects animals from the development of cisplatin-induced polyneuropathy, and there are no sex differences. Trif(lps2) male mice show a persistent tactile allodynia following cisplatin administration, while female mice show a reduced allodynia, and remain higher in threshold than their male counterparts. On day 18, animals were given the analgesic gabapentin, and thresholds were tested 45 min after. Gabapentin was effective in transiently reversing mechanical allodynia in those mice with lowered thresholds. CONCLUSIONS: It is important to continue examining both sexes in various pain models, as a mononeuropathy and polyneuropathy show sex differences in pain development and the role of TLR signalling.
Authors: A Tesniere; F Schlemmer; V Boige; O Kepp; I Martins; F Ghiringhelli; L Aymeric; M Michaud; L Apetoh; L Barault; J Mendiboure; J-P Pignon; V Jooste; P van Endert; M Ducreux; L Zitvogel; F Piard; G Kroemer Journal: Oncogene Date: 2009-11-02 Impact factor: 9.867
Authors: Floortje Mols; Tonneke Beijers; Gerard Vreugdenhil; Lonneke van de Poll-Franse Journal: Support Care Cancer Date: 2014-05-01 Impact factor: 3.603
Authors: Robert E Sorge; Loren J Martin; Kelsey A Isbester; Susana G Sotocinal; Sarah Rosen; Alexander H Tuttle; Jeffrey S Wieskopf; Erinn L Acland; Anastassia Dokova; Basil Kadoura; Philip Leger; Josiane C S Mapplebeck; Martina McPhail; Ada Delaney; Gustaf Wigerblad; Alan P Schumann; Tammie Quinn; Johannes Frasnelli; Camilla I Svensson; Wendy F Sternberg; Jeffrey S Mogil Journal: Nat Methods Date: 2014-04-28 Impact factor: 28.547
Authors: Sarah A Woller; Soo-Ho Choi; Eun Jung An; Hann Low; Dina A Schneider; Roshni Ramachandran; Jungsu Kim; Yun Soo Bae; Dmitri Sviridov; Maripat Corr; Tony L Yaksh; Yury I Miller Journal: Cell Rep Date: 2018-05-29 Impact factor: 9.423
Authors: Sarah A Woller; Cody Ocheltree; Stephanie Y Wong; Anthony Bui; Yuya Fujita; Gilson Gonçalves Dos Santos; Tony L Yaksh; Maripat Corr Journal: Brain Behav Immun Date: 2018-11-19 Impact factor: 7.217
Authors: Sarah A Woller; Satheesh B Ravula; Fabio C Tucci; Graham Beaton; Maripat Corr; R Rivkah Isseroff; Athena M Soulika; Marianne Chigbrow; Kelly A Eddinger; Tony L Yaksh Journal: Brain Behav Immun Date: 2016-04-01 Impact factor: 7.217