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A Hyperresponsive HPA Axis May Confer Resilience Against Persistent Paclitaxel-Induced Mechanical Hypersensitivity
Sharon L Kozachik1, Gayle G Page2
1School of Nursing, Johns Hopkins University, Baltimore, MD, USA skozach1@jhu.edu.
Biological Research for Nursing
|October 30, 2015
Summary
Paclitaxel (PAC) treatment can cause neuropathic pain. Rats with moderate hypothalamic-pituitary-adrenal (HPA) axis stress responsivity showed increased PAC-induced pain, suggesting a potential risk factor for developing this side effect.
Area of Science:
- Neuroscience
- Pharmacology
- Pain Research
Background:
- Paclitaxel (PAC) chemotherapy can lead to debilitating neuropathic pain.
- Female sex and stress responsivity are known risk factors for persistent pain.
- The specific risk conferred by these factors for PAC-induced pain remains unclear.
Purpose of the Study:
- To investigate the roles of sex and hypothalamic-pituitary-adrenal (HPA) axis stress responsivity in paclitaxel-induced neuropathic pain.
- To determine if differences in HPA axis activity influence the severity of PAC-induced mechanical hypersensitivity.
Main Methods:
- A 42-day paclitaxel (PAC) administration protocol was used in male and female Fischer 344, Lewis, and Sprague Dawley (SD) rats.
- Rats differ in their baseline HPA axis stress responsivity.
- Mechanical sensitivity was measured using the von Frey filament up-down method.
Main Results:
- Sprague Dawley (SD) rats, with moderate HPA axis responsivity, showed significantly greater PAC-induced mechanical hypersensitivity compared to Fischer 344 rats.
- PAC-treated Fischer 344 rats exhibited resilience to long-term hypersensitivity.
- Sex differences in hypersensitivity were observed but were transient and only present early in the PAC protocol.
Conclusions:
- Moderate HPA axis stress responsivity may increase the risk of developing painful side effects from paclitaxel (PAC) treatment.
- These findings suggest that HPA axis activity could be a biomarker for identifying patients at higher risk for PAC-induced neuropathic pain.
- Further research is needed to validate these findings in human populations.
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