Bidirectional selection for high and low stress-induced analgesia affects G-protein activity

Poznański, Piotr; Leśniak, Anna; Bujalska‐Zadrożny, Magdalena; Strzemecka, Joanna; Sacharczuk, Mariusz

doi:10.1016/j.neuropharm.2018.10.014

Cited by 15 publications

(9 citation statements)

References 49 publications

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“…Our current investigation clearly showed that the HA mice presented significantly less nocifensive behaviours in the interphase than the LA mice ( Figure 1 ). Thus, we hypothesized that this active inhibitory mechanism could be attributed to the endocannabinoid system, as our previous studies indicated substantial differences in its activity between HA and LA mice [ 17 , 36 ]. The HA mice showed a significant increase in spinal and amygdalar Cnr1 transcripts ( Table 1 ), while Cnr2 mRNA levels were elevated only in the amygdala ( Table 2 ).…”

Section: Discussionmentioning

confidence: 99%

Mechanisms Underlining Inflammatory Pain Sensitivity in Mice Selected for High and Low Stress-Induced Analgesia—The Role of Endocannabinoids and Microglia

Poznański

Giebułtowicz

Durdzinska

et al. 2022

IJMS

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In this work we strived to determine whether endocannabinoid system activity could account for the differences in acute inflammatory pain sensitivity in mouse lines selected for high (HA) and low (LA) swim-stress-induced analgesia (SSIA). Mice received intraplantar injections of 5% formalin and the intensity of nocifensive behaviours was scored. To assess the contribution of the endocannabinoid system, mice were intraperitoneally (i.p.) injected with rimonabant (0.3–3 mg/kg) prior to formalin. Minocycline (45 and 100 mg/kg, i.p.) was administered to investigate microglial activation. The possible involvement of the endogenous opioid system was investigated with naloxone (1 mg/kg, i.p.). Cannabinoid receptor types 1 and 2 (Cnr1, Cnr2) and opioid receptor subtype (Oprm1, Oprd1, Oprk1) mRNA levels were quantified by qPCR in the structures of the central nociceptive circuit. Levels of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) were measured by liquid chromatography coupled with the mass spectrometry method (LC-MS/MS). In the interphase, higher pain thresholds in the HA mice correlated with increased spinal anandamide and 2-AG release and higher Cnr1 transcription. Downregulation of Oprd1 and Oprm1 mRNA was noted in HA and LA mice, respectively, however no differences in naloxone sensitivity were observed in either line. As opposed to the LA mice, inflammatory pain sensitivity in the HA mice in the tonic phase was attributed to enhanced microglial activation, as evidenced by enhanced Aif1 and Il-1β mRNA levels. To conclude, Cnr1 inhibitory signaling is one mechanism responsible for decreased pain sensitivity in HA mice in the interphase, while increased microglial activation corresponds to decreased pain thresholds in the tonic inflammatory phase.

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Section: Discussionmentioning

confidence: 99%

Mechanisms Underlining Inflammatory Pain Sensitivity in Mice Selected for High and Low Stress-Induced Analgesia—The Role of Endocannabinoids and Microglia

Poznański

Giebułtowicz

Durdzinska

et al. 2022

IJMS

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“…HA mice express higher peripheral β– endorphin levels, whereas LA mice have low sensitivity to morphine. However, no striking differences in opioid receptor expression or binding were noted between HA or LA mice [ 16 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, mice selected for high activity of the opioid endogenous system exert some neurological symptoms which are also present in hypertensive patients and which are absent in other models. For example, NLX selectively induces high levels of anxiety- and depressive-like behaviors in HA mice [ 16 ]. It is known that patients with depression and/or anxiety represent a particularly vulnerable population as they are at higher risk for developing hypertension [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, another study shows that opioids’ effect on BP level depends on the hypertension model used in the study [ 15 ]. Therefore, we aimed to characterize vascular function and BP level in a unique model of mice selected for high and low activity of the endogenous opioid system [ 16 , 17 ]. Mice selected for high (HA) and low (LA) swim stress-induced analgesia (SSIA) are characterized by unique, inherited differences in opioid system activity [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

“…Mice selected for high (HA) and low (LA) swim stress-induced analgesia (SSIA) are characterized by unique, inherited differences in opioid system activity [ 18 ]. HA mice exhibited increased opioid system activity as compared to their LA counterparts and showed enhanced G-protein activity in central nervous system structures involved in pain modulation [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Hypertensive Effect of Downregulation of the Opioid System in Mouse Model of Different Activity of the Endogenous Opioid System

Skiba

Szczepaniak

Siedliński

et al. 2021

IJMS

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The opioid system is well-known for its role in modulating nociception and addiction development. However, there are premises that the endogenous opioid system may also affect blood pressure. The main goal of the present study was to determine the impact of different endogenous opioid system activity and its pharmacological blockade on blood pressure. Moreover, we examined the vascular function in hyper- and hypoactive states of the opioid system and its pharmacological modification. In our study, we used two mouse lines which are divergently bred for high (HA) and low (LA) swim stress-induced analgesia. The obtained results indicated that individuals with low endogenous opioid system activity have higher basal blood pressure compared to those with a hyperactive opioid system. Additionally, naloxone administration only resulted in the elevation of blood pressure in HA mice. We also showed that the hypoactive opioid system contributes to impaired vascular relaxation independent of endothelium, which corresponded with decreased guanylyl cyclase levels in the aorta. Together, these data suggest that higher basal blood pressure in LA mice is a result of disturbed mechanisms in vascular relaxation in smooth muscle cells. We believe that a novel mechanism which involves endogenous opioid system activity in the regulation of blood pressure will be a promising target for further studies in hypertension development.

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Intra-CA1 injection of orexin receptors antagonism attenuates the stress-induced analgesia in a rat acute pain model

Ghalebandi

Zareie

Askari

et al. 2022

Behavioural Brain Research

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Bidirectional selection for high and low stress-induced analgesia affects G-protein activity

Cited by 15 publications

References 49 publications

Mechanisms Underlining Inflammatory Pain Sensitivity in Mice Selected for High and Low Stress-Induced Analgesia—The Role of Endocannabinoids and Microglia

Mechanisms Underlining Inflammatory Pain Sensitivity in Mice Selected for High and Low Stress-Induced Analgesia—The Role of Endocannabinoids and Microglia

Hypertensive Effect of Downregulation of the Opioid System in Mouse Model of Different Activity of the Endogenous Opioid System

Intra-CA1 injection of orexin receptors antagonism attenuates the stress-induced analgesia in a rat acute pain model

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