17β-Estradiol Mediates the Sex Difference in Capsaicin-Induced Nociception in Rats

Lu, Yu-Ching; Chen, Chao-Wei; Wang, Su-Yi; Wu, Fong‐Sen

doi:10.1124/jpet.109.158402

Cited by 62 publications

(65 citation statements)

References 39 publications

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“…Previous study results have led to contradictive conclusions. Research results have reported stronger antinociceptive action of morphine in the pro-oestrus and dioestrus phases as compared to the oestrus phase (hot plate test at 50°C) [22], increased pain sensitivity in the metoestrus and dioestrus phase as compared to pro-oestrus and oestrus phases, that is in phases characterized by low sex hormone levels (hot tail and tail immersion tests) [23], and much higher nociceptive action after administration of capsaicin s.c. in the pro-oestrus as compared to the oestrus phase (chemical pain stimulus) [24]. These contradicting results could be caused by a number of factors.…”

Section: Discussioncontrasting

confidence: 40%

Morphine Analgesia Modification in Normotensive and Hypertensive Female Rats after Repeated Fluoxetine Administration

Kosiorek-Witek

Makulska-Nowak

2015

Basic Clin Pharma Tox

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The purpose of this investigation was to determine through the use of fluoxetine the effect of administering a serotonin reuptake inhibitor over several days on the antinociceptive action of l-morphine type opioid receptor agonist. Investigations were performed on rats of both sexes, both the WKY normotensive strains as well as on the SHR genetically conditioned hypertensive strains. Results showed that the efficacy of morphine analgesia is higher in the SHR strain compared to normotensive rats (WKY). Surprisingly, repeated administration of fluoxetine reduced morphine analgesia, with the weakening of opioid antinociceptive action comparable to the duration of serotonin reuptake inhibitor administration. It was also concluded that the antinociceptive action of morphine in female rats and the alteration of its efficacy as a result of fluoxetine premedication for several days depend on oestrus cycle phase. The highest sensitivity of female rats to morphine was reported in the dioestrus and oestrus phases; much lower values were reported for the metoestrus phase.For decades, young male rats have been the basic group of animals used in research addressing the pharmacological consequences of administering drugs, with research results being extrapolated to the entire population. It is now well-known that males and females may react differently to the administration of drugs. Significant differences have been reported for lmorphine type opioid receptor agonist, which exhibits distinct sexual dimorphism. Sex-dependent differentiation has been reported for sensitivity to analgesic action of such a l-type opioid receptor agonist [1][2][3][4], quickness in developing tolerance and dependence [5], as well as release substance P [6]. Also, a number of investigations have confirmed the influence of morphine on the functioning of the female sexual system. It has been reported that chronic administration of morphine disrupts the oestrus cycle [5]. The effect of sex hormones on the development of sex-dependent differentiation is also shown by the fact that many sex dimorphic features only develop postpuberty. Neither sex-dependent differentiation in heart rate [7] nor pain sensitivity in the case of many pain conditions [8,9] has been reported pre-puberty. It has also been shown that sex steroids modulate large-artery stiffness, thus -in addition to genetic factors -affecting frequency of isolated systolic hyperpressure occurrence [7].Patients treated with morphine often also require use of antidepressants, which include selective serotonin reuptake inhibitors (SSRI). No complete mechanism of SSRI antinociceptive action has yet been offered. Due to the more effective performance analgesic action of fluoxetine compared to the placebo in patients with depression, it is possible that its analgesic efficacy could be related to antidepressant activity [10]. Its place of action could be the same as for the l-type opioid receptor agonists [11], but antinociceptive action could also involve the cholinergic, noradrenergic and G...

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Section: Discussioncontrasting

confidence: 40%

Morphine Analgesia Modification in Normotensive and Hypertensive Female Rats after Repeated Fluoxetine Administration

Kosiorek-Witek

Makulska-Nowak

2015

Basic Clin Pharma Tox

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“…capsaicin. The number of flinches and the time spent licking or lifting (s) the affected hindpaw were combined and reported as the number of nociceptive responses, where 1 s of licking/lifting is equal to one flinch response [1;49;78]. Sham injections consisted of capsaicin vehicle as a control.…”

Section: Methodsmentioning

confidence: 99%

Pioglitazone rapidly reduces neuropathic pain through astrocyte and nongenomic PPARγ mechanisms

Griggs

Donahue

Morgenweck

et al. 2015

Pain

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Repeated administration of peroxisome proliferator-activated receptor gamma (PPARγ) agonists reduces neuropathic pain-like behavior and associated changes in glial activation in the spinal cord dorsal horn. As PPARγ is a nuclear receptor, sustained changes in gene expression are widely believed to be the mechanism of pain reduction. However, we recently reported that a single intrathecal injection of pioglitazone, a PPARγ agonist, reduced hyperalgesia within 30 minutes, a time frame that is typically less than that required for genomic mechanisms. To determine the very rapid anti-hyperalgesic actions of PPARγ activation we administered pioglitazone to rats with spared nerve injury (SNI) and evaluated hyperalgesia. Pioglitazone inhibited hyperalgesia within 5 min of injection, consistent with a non-genomic mechanism. Systemic or intrathecal administration of GW9662, a PPARγ antagonist, inhibited the anti-hyperalgesic actions of intraperitoneal or intrathecal pioglitazone, suggesting a spinal PPARγ-dependent mechanism. To further address the contribution of non-genomic mechanisms, we blocked new protein synthesis in the spinal cord with anisomycin. When co-administered intrathecally, anisomycin did not change pioglitazone anti-hyperalgesia at an early 7.5 min timepoint, further supporting a rapid non-genomic mechanism. At later timepoints anisomycin reduced pioglitazone anti-hyperalgesia, suggesting a delayed recruitment of genomic mechanisms. Pioglitazone reduction of SNI-induced increases in GFAP expression occurred more rapidly than expected, within 60 min. We are the first to show that activation of spinal PPARγ rapidly reduces neuropathic pain independent from canonical genomic activity. We conclude that acute pioglitazone inhibits neuropathic pain in part by reducing astrocyte activation, and via both genomic and non-genomic PPARγ mechanisms.

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“…45 Importantly, TRPV1-induced changes in current were not assessed in either of these studies as neither was the phosphorylation status of TRPV1. Separately, increased capsaicininduced nociception was apparent in female rats compared with male rats, 46 a response that was shown to be independent of PKA activity. The apparently conflicting findings in these studies may be a reflection of differences in the concentrations of the estrogens used, and further investigation of the impact of sex hormones, both male and female, on the vascular effects of TRPV1 is warranted.…”

Section: 32mentioning

confidence: 99%

Activation of Neuronal Transient Receptor Potential Vanilloid 1 Channel Underlies 20-Hydroxyeicosatetraenoic Acid–Induced Vasoactivity

et al. 2013

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Abstract-A rise in intraluminal pressure triggers vasoconstriction in resistance arteries, which is associated with local generation of the vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE). Importantly, dysregulation of 20-HETE synthesis and activity has been implicated in several cardiovascular disease states, including ischemic disease, hypertension, and stroke; however, the exact molecular pathways involved in mediating 20-HETE bioactivity are uncertain. We investigated whether 20-HETE activates the transient receptor potential vanilloid 1 (TRPV1) and thereby regulates vascular function and blood pressure. We demonstrate that 20-HETE causes dose-dependent increases in blood pressure, coronary perfusion pressure (isolated Langendorff), and pressure-induced constriction of resistance arteries (perfusion myography) that is substantially attenuated in TRPV1 knockout mice and by treatment with the neurokinin 1 receptor antagonist RP67580. Furthermore, we show that both channel activation (via patch-clamping of dorsal root ganglion neurons) and vessel constriction are enhanced under inflammatory conditions, and our findings indicate a predominant role for protein kinase A-mediated sensitization of TRPV1 in these phenomena. Finally, we identify a prominence of these pathway in males compared with females, an effect we relate to reduced protein kinase A-induced phosphorylation of TRPV1. 20-HETE-induced activation of TRPV1, in part, mediates pressure-induced myogenic constriction and underlies 20-HETE-induced elevations in blood pressure and coronary resistance.

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17β-Estradiol Mediates the Sex Difference in Capsaicin-Induced Nociception in Rats

Cited by 62 publications

References 39 publications

Morphine Analgesia Modification in Normotensive and Hypertensive Female Rats after Repeated Fluoxetine Administration

Morphine Analgesia Modification in Normotensive and Hypertensive Female Rats after Repeated Fluoxetine Administration

Pioglitazone rapidly reduces neuropathic pain through astrocyte and nongenomic PPARγ mechanisms

Activation of Neuronal Transient Receptor Potential Vanilloid 1 Channel Underlies 20-Hydroxyeicosatetraenoic Acid–Induced Vasoactivity

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