Sexual dimorphism for protein kinase cε signaling in a rat model of vincristine-induced painful peripheral neuropathy
Section snippets
Animals
Experiments were performed on male and female Sprague–Dawley rats (220–250 g, Bantin and Kingman, Fremont, CA, USA). Rats were housed in groups of two under a 12-h light/dark cycle. Food and water were available ad libitum. Experiments were carried out in accordance with NIH regulations for animal care and with the approval of the Institutional Animal Care and Use Committee of the University of California, San Francisco. All efforts were made to minimize the number of animals used and their
Vcr-induced mechanical hyperalgesia
A single i.v. injection of VCR, 50, 100 and 200 μg/kg, to male and female rats produced a dose-dependent decrease in nociceptive threshold that persisted for a period of at least 15 days. The magnitude of this mechanical hyperalgesia was greater in female rats at all doses and time points (Fig. 1A–C, n=8/group; Table 1).
Vcr-induced mechanical allodynia
Both male and female rats demonstrated a significant increase in paw-withdrawal frequency in response to 1.3-, 3.6-, 10- and 27.5-mN von Frey stimulation, tested 5 days after a
Discussion
Vinca alkaloids such as VCR, are widely used alone or in combination with other chemotherapeutic agents in the treatment of many different malignancies including breast cancer, leukemias, lymphomas, and primary brain tumors Di Cataldo et al., 2002, Ito et al., 2002, Kochi and Ushio, 2002, Robak et al., 2002. VCR kills mitotically active cells by binding tubulin and preventing microtubule formation in mitotic spindles Mahboobi et al., 2001, Blajeski et al., 2002. Tumor cells are most effectively
Acknowledgements
Funded by NIH grant DE08973. We thank Dr. Robert Gear for his helpful suggestions and assistance in the statistical analysis of the data.
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ThermoTRP channels in pain sexual dimorphism: new insights for drug intervention
2022, Pharmacology and TherapeuticsCitation Excerpt :In particular, testosterone concentration in the sciatic nerve was higher in males whereas 17-β-estradiol and progesterone derivatives (dihydroprogesterone, tetrahydroprogesterone) were increased in females, suggesting that a specific hormonally-activated pathway may be predominating in each sex. An estrogen-dependent sexual dimorphism was also found in rats treated with vincristine, where removal of the hormone abolished the greater mechanical hypersensitivity found in female rats when compared to males (Joseph & Levine, 2003). In this study, inhibition of PKC-ε, a modulator of TRPV1 activity, reduced vincristine-induced hyperalgesia in males and ovariectomized females (Joseph & Levine, 2003), suggesting that estrogens could generate hyperalgesia in females by promoting TRPV1 signaling (Goswami et al., 2011).
Neuropathic Pain models caused by damage to central or peripheral nervous system
2018, Pharmacological ReportsAromatase inhibitors augment nociceptive behaviors in rats and enhance the excitability of sensory neurons
2016, Experimental NeurologyCitation Excerpt :Our observed differences in the time course of nociceptive behavior between males and OVX females given the treatment regimens could be secondary to sex differences mediating nociception and analgesia, as have been suggested by many clinical and pre-clinical pain studies (Craft et al., 2004). For example, differences between males and females have been observed in the nociceptive response to capsaicin (Lu et al., 2009), in animal models of chemotherapy-induced peripheral neuropathy (Joseph and Levine, 2003), and in nociceptive changes due to inflammation (Mannino et al., 2007). These differences are often attributed to multiple factors, including the organizational and activational consequences of reproductive hormone differences between sexes.