Activation of peripheral delta-opioid receptors leads to anti-hyperalgesic responses in the masseter muscle of male and female rats

Saloman, Jami L.; Niu, Katelyn Y.; Ro, Jin Y.

doi:10.1016/j.neuroscience.2011.05.062

Cited by 39 publications

(27 citation statements)

References 51 publications

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“…Consistent with these observations we have recently shown that capsaicin-induced masseter hypersensitivity is attenuated by direct activation of δ opioid receptors (DOR) in TG and that the DOR-mediated anti-hyperalgesic responses are reversed when KATP is blocked by a specific KATP antagonist, glibenclamide (Saloman et al, 2010). Interestingly, the DOR-mediated responses were significantly more potent in male compared to female rats.…”

Section: Discussionsupporting

confidence: 58%

Sex differences in the contribution of ATP-sensitive K+ channels in trigeminal ganglia under an acute muscle pain condition

Niu¹,

Saloman²,

Zhang³

et al. 2011

Neuroscience

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In this study, we examined whether functional subunits of the ATP-dependent K + channel (KATP) are expressed in trigeminal ganglia (TG), which contains sensory neurons that innervate oral and facial structures. We also investigated whether direct activation of the KATP effectively attenuates mechanical hypersensitivity in the context of an acute orofacial muscle pain condition. The KATP expression in TG and behavioral studies were conducted in age matched male and female Sprague Dawley rats. RT-PCR experiments showed that the mRNAs for the inwardly rectifying poreforming subunits, Kir6.1 and Kir6.2, as well as the regulatory sulphonylurea subunits, SUR1 and SUR2, were reliably detected in TG. Subsequent western blot analysis confirmed that proteins for all 4 subunits are expressed in TG, and showed that Kir6.2 is expressed at a significantly higher level in male TG compared to that of female rats. This observation was confirmed by the immunohistochemical demonstration of higher percentages of Kir6 positive masseter afferents in female rats. Masseteric injection of capsaicin evokes a time dependent increase in masseter sensitivity to noxious mechanical stimulation. A specific KATP agonist, pinacidil, dosedependently attenuated the capsaicin-induced mechanical hypersensitivity in male rats. The dose of pinacidil (20µg) that completely blocked the capsaicin responses in male rats was ineffective in female rats regardless of their estrus phases. Only at the highest dose (300µg) we used, pinacidil was partially effective in female rats. Similarly, another KATP agonist, diazoxide which targets different KATP subunits also showed sex specific responses in attenuating capsaicin-induced masseter hypersensitivity. These data suggested that sex differences in functional KATP expression in TG may underlie sex specific responses to KATP agonists. The present study provided novel information on sex differences in KATP expression in TG and its contribution under an orofacial muscle pain condition.

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Section: Discussionsupporting

confidence: 58%

Sex differences in the contribution of ATP-sensitive K+ channels in trigeminal ganglia under an acute muscle pain condition

Niu¹,

Saloman²,

Zhang³

et al. 2011

Neuroscience

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“…It is also important to note that pre-clinical studies demonstrating the effectiveness of peripheral opioid receptors are continuously being accumulated, even including those under neuropathic pain conditions (Shinoda et al, 2007; Guan et al, 2008; Sánchez et al, 2010; Saloman et al, 2011; Auh and Ro, 2012; Martins et al, 2012; Ni et al, 2013). Therefore, peripheral opioid receptors still remain as a viable target for pain management, especially under inflammatory conditions, and additional human experimental as well as clinical studies are definitely warranted.…”

Section: Discussionmentioning

confidence: 99%

Sex differences in μ‐opioid receptor expression in trigeminal ganglia under a myositis condition in rats

Zhang

Asgar

et al. 2013

European Journal of Pain

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Background Peripheral opioid receptor expression is up-regulated under inflammatory conditions, which leads to the increased efficacy of peripherally administered opioids. Sex differences in the effects of inflammation, cytokines and gonadal hormones on μ–opioid receptor (MOR) expression in trigeminal ganglia (TG) are not well understood. Methods MOR mRNA and protein levels in TG from male and female Sprague Dawley rats following complete Freund’s adjuvant (CFA)-induced muscle inflammation were assessed. Cytokine-induced changes in MOR mRNA expression from TG cultures prepared from intact and gonadectomized male and female, and gonadectomzed male rats with testosterone replacement were examined. Behavioral experiments were then performed to examine the efficacy of a peripherally administered MOR agonist in male, female and gonadectomized male rats under a myositis condition. Results CFA and cytokine treatments induced significant up-regulation of MOR expression in TG from male, but not from female, rats. The cytokine-induced up-regulation of MOR mRNA expression was prevented in TG from orchidectomized (GDX) male rats, which was restored with testosterone replacement. Peripherally administered DAMGO, a specific MOR agonist, significantly attenuated CFA-induced masseter mechanical hypersensitivity only in intact male rats. Conclusions Collectively, these data indicate that testosterone plays a key role in the regulation of MOR in TG under inflammatory conditions, and that sex differences in the anti-hyperalgesic effects of peripherally administered opioids are, in part, mediated by peripheral opioid receptor expression levels.

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“…In particular, it is known that release of intracellular Ca +2 stores by Gq-coupled receptors activates CaMKII, which stimulates neuronal nitric oxide synthase and nitric oxide release leading to cGMP production and protein kinase G-mediated activation of K ATP channels; this then produces analgesia via hyperpolarization of primary afferents (Gong et al, 2015). A direct association of this cascade with antinociceptive actions of peripherally administered DOPr agonists is suggested by the fact by K ATP blockers, neuronal nitric oxide synthase inhibitors, and inactive cGMP analogs all interfere with DOPr-mediated analgesia (Pacheco and Duarte, 2005;Saloman et al, 2011;Gutierrez et al, 2012).…”

Section: D-opioid Receptors and Phospholipase Signalingmentioning

confidence: 99%

Molecular Pharmacology ofδ-Opioid Receptors

et al. 2016

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Activation of peripheral delta-opioid receptors leads to anti-hyperalgesic responses in the masseter muscle of male and female rats

Cited by 39 publications

References 51 publications

Sex differences in the contribution of ATP-sensitive K+ channels in trigeminal ganglia under an acute muscle pain condition

Sex differences in the contribution of ATP-sensitive K+ channels in trigeminal ganglia under an acute muscle pain condition

Sex differences in μ‐opioid receptor expression in trigeminal ganglia under a myositis condition in rats

Molecular Pharmacology ofδ-Opioid Receptors

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