Sex differences in hypothalamic-mediated tonic norepinephrine release for thermal hyperalgesia in rats

Pain condition and sex differences in the descending noradrenergic system following lateral hypothalamic stimulation

“…However, with the CCI data, both females and males demonstrated significantly longer TPW following blockade of α 1 -adrenoceptors with WB4101, while neither females nor males demonstrated any significant differences between yohimbine and saline (data not shown). These findings replicate those reported from earlier work (Wagner et al, 2016).…”

“…3). We have shown that α 1 -, but not α 2 -adrenoceptors are tonically active in both CCI males and females, with the CCI rats showing significantly greater responses than the naïve rats (Wagner et al, 2016). Findings from the present study, in which we gave only IT antagonists, support these earlier findings of tonic α 1 -adrenoceptor activity.…”

“…The opposing effects of pronociceptive α 1 - and antinociceptive α 2 -adrenoceptors occur in naïve females (Holden land Naleway, 2001) and in females with persistent inflammatory pain (Jeong and Holden, 2009); 3. Tonic activation of α 1 - but not α 2 -adrenoceptors occurs in naïve and CCI rats, with a much greater effect in CCI rats (Wagner et al, 2016); 4. Both α 1 - (Roudet et al, 1993, 1994; Xie et al, 2001) and α 2 -adrenoceptors (Roudet et al, 1993, 1994) up-regulate following nerve injury; 5.…”

Identification of WB4101, anα1-Adrenoceptor Antagonist, as a Sodium Channel Blocker

“…The expression of α-adrenoceptors appeared to be increased in neuropathic pain models (Drummond et al, 2014a;Drummond et al, 2014b). Thus the antagonism of WB4101 on α-adrenoceptor was considered as its mechanism for its pain relief (Holden and Nalway, 2001;Holden et al, 1999;Wagner et al, 2016). It is well known that ion channels (especially sodium channels and calcium channels) are novel therapeutic targets in the treatment of pain (Mathie, 2010).…”

“…Similarly, WB4101 (Kapur et al, 1978), as an alpha1-adrenoceptor selective antagonist, was also found to be an effective antihyperalgesic agent in multiple pain models, including nociceptive and neuropathic pain (Holden and Nalway, 2001;Holden et al, 1999;Wagner et al, 2016).…”