TY - JOUR
T1 - A Hyperresponsive HPA Axis May Confer Resilience Against Persistent Paclitaxel-Induced Mechanical Hypersensitivity
AU - Kozachik, Sharon L.
AU - Page, Gayle G.
N1 - Publisher Copyright:
© The Author(s) 2015.
PY - 2015/5
Y1 - 2015/5
N2 - Paclitaxel (PAC) treatment is associated with persistent, debilitating neuropathic pain that affects the hands and feet. Female sex and biological stress responsivity are risk factors for persistent pain, but it is unclear whether these important biologically based factors confer risk for PAC-induced neuropathic pain. To determine the relative contributions of sex and hypothalamic–pituitary–adrenal (HPA)-axis stress responsivity to PAC-induced mechanical hypersensitivity, we employed a PAC protocol consisting of three, 2-week cycles of every-other-day doses of PAC 1 mg/kg versus saline (Week 1) and recovery (Week 2), totaling 42 days, in mature male and female Fischer 344, Lewis, and Sprague Dawley (SD) rats, known to differ in HPA axis stress responsivity. Mechanical sensitivity was operationalized using von Frey filaments, per the up–down method. Among PAC-injected rats, SD rats exhibited significantly greater mechanical hypersensitivity relative to accumulative PAC doses compared to Fischer 344 rats. Lewis rats were not significantly different in mechanical hypersensitivity from SD or Fischer 344 rats. At the end of the protocol, PAC-injected SD rats exhibited profound mechanical hypersensitivity, whereas the PAC-injected Fischer 344 rats appeared relatively resilient to the long-term effects of PAC and exhibited mechanical sensitivity that was not statistically different from their saline-injected counterparts. Sex differences were mixed and noted only early in the PAC protocol. Moderate HPA axis stress responsivity may confer additional risk for the painful effects of PAC. If these findings hold in humans, clinicians may be better able to identify persons who may be at increased risks for developing neuropathic pain during PAC therapy.
AB - Paclitaxel (PAC) treatment is associated with persistent, debilitating neuropathic pain that affects the hands and feet. Female sex and biological stress responsivity are risk factors for persistent pain, but it is unclear whether these important biologically based factors confer risk for PAC-induced neuropathic pain. To determine the relative contributions of sex and hypothalamic–pituitary–adrenal (HPA)-axis stress responsivity to PAC-induced mechanical hypersensitivity, we employed a PAC protocol consisting of three, 2-week cycles of every-other-day doses of PAC 1 mg/kg versus saline (Week 1) and recovery (Week 2), totaling 42 days, in mature male and female Fischer 344, Lewis, and Sprague Dawley (SD) rats, known to differ in HPA axis stress responsivity. Mechanical sensitivity was operationalized using von Frey filaments, per the up–down method. Among PAC-injected rats, SD rats exhibited significantly greater mechanical hypersensitivity relative to accumulative PAC doses compared to Fischer 344 rats. Lewis rats were not significantly different in mechanical hypersensitivity from SD or Fischer 344 rats. At the end of the protocol, PAC-injected SD rats exhibited profound mechanical hypersensitivity, whereas the PAC-injected Fischer 344 rats appeared relatively resilient to the long-term effects of PAC and exhibited mechanical sensitivity that was not statistically different from their saline-injected counterparts. Sex differences were mixed and noted only early in the PAC protocol. Moderate HPA axis stress responsivity may confer additional risk for the painful effects of PAC. If these findings hold in humans, clinicians may be better able to identify persons who may be at increased risks for developing neuropathic pain during PAC therapy.
KW - Fischer 344
KW - Lewis
KW - Sprague Dawley
KW - neuropathic pain
KW - rats
UR - http://www.scopus.com/inward/record.url?scp=84963652765&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84963652765&partnerID=8YFLogxK
U2 - 10.1177/1099800415609418
DO - 10.1177/1099800415609418
M3 - Article
C2 - 26512050
AN - SCOPUS:84963652765
SN - 1099-8004
VL - 18
SP - 290
EP - 298
JO - Biological Research For Nursing
JF - Biological Research For Nursing
IS - 3
ER -