Antinociception Versus Serum Concentration Relationships Following Acute Administration of Intravenous Morphine in Male and Female Sprague‐dawley Rats: Differences Between the Tail Flick and Hot Plate Nociceptive Tests

South, S. M.; Edwards, Stephen R.; Smith, Maree T.

doi:10.1111/j.1440-1681.2008.05019.x

Cited by 31 publications

(22 citation statements)

References 25 publications

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“…Less frequent, but still abundant, are the reports where a compound or condition influences the response to one of the tests but fails in the other (23)(24)(25)(26). On the other hand, studies where the two tests render opposite effects are more difficult to find.…”

Section: Discussionmentioning

confidence: 92%

Lack of Adrenomedullin in the Central Nervous System Results in Apparently Paradoxical Alterations on Pain Sensitivity

et al. 2010

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Adrenomedullin (AM) is a regulatory peptide, coded by the adm gene, which is involved in numerous physiological processes, including pain sensitivity. Previous studies have shown that intrathecal injection of AM induced hyperalgesia in the rat. Here, we explore pain sensitivity in a mouse conditional knockout for adm in neurons of the central nervous system, including the spinal cord and dorsal root ganglia. Double immunofluorescence in wild-type (WT) animals shows that AM immunoreactivity is found in calcitonin gene-related peptide-positive neurons of the dorsal root ganglia but not in neurons that bind isolectin B4. Mice lacking adm had modified expression of canonical sensorial neuropeptides, having significantly more calcitonin gene-related peptide and less substance P and enkephalin than their WT littermates. Furthermore, the spinal cord of adm knockout mice expressed higher levels of the AM receptor components, suggesting a compensation attempt to deal with the lack of afferent AM signaling. Behavioral nociceptive tests also found differences between genotypes. In the tail-flick test, which measures mostly spinal reflexes, the adm-null animals had a longer latency than their WT counterparts. On the other hand, in the hotplate test, which requires encephalic processing, mice lacking adm had shorter latencies than normal littermates. These results suggest that AM acts as a nociceptive modulator in spinal reflexes, whereas it may have an analgesic function at higher cognitive levels. This study confirms the important role of AM in pain sensitivity processing but unveils a more complex scenario than previously surmised.

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Section: Discussionmentioning

confidence: 92%

Lack of Adrenomedullin in the Central Nervous System Results in Apparently Paradoxical Alterations on Pain Sensitivity

et al. 2010

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“…In rats, the disposition of morphine and its major biologically-active metabolite, morphine-3-glucuronide, after peripheral administration have been investigated extensively (see Smith et al, 1990; Alnouti et al, 2007; South et al, 2009). For example, South et al (2009) reported that following intravenous injection of a 10 mg/kg dose of morphine to male Sprague-Dawley rats (same dose and route of administration, and rat and gender strain as used in the present study), the blood levels of morphine (all approximate values read from the manuscript figs) peaked at 7 μΜ at 2.5 minutes (time of initial maximal effects in our study) and were at 1 μΜ at 50 minutes (time of last measurement in our study when many effects of morphine were still sustained).…”

Section: Discussionmentioning

confidence: 99%

“…For example, South et al (2009) reported that following intravenous injection of a 10 mg/kg dose of morphine to male Sprague-Dawley rats (same dose and route of administration, and rat and gender strain as used in the present study), the blood levels of morphine (all approximate values read from the manuscript figs) peaked at 7 μΜ at 2.5 minutes (time of initial maximal effects in our study) and were at 1 μΜ at 50 minutes (time of last measurement in our study when many effects of morphine were still sustained). In addition, blood concentrations of morphine-3-glucuronide were 7.5 μΜ at 2.5 minutes and 7 μΜ at 50 minutes.…”

Section: Discussionmentioning

confidence: 99%

Bilateral carotid sinus nerve transection exacerbates morphine-induced respiratory depression

Baby¹,

Gruber²,

Young

et al. 2018

European Journal of Pharmacology

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Opioid-induced respiratory depression (OIRD) involves decreased sensitivity of ventilatory control systems to decreased blood levels of oxygen (hypoxia) and elevated levels of carbon dioxide (hypercapnia). Understanding the sites and mechanisms by which opioids elicit respiratory depression is pivotal for finding novel therapeutics to prevent and/or reverse OIRD. To examine the contribution of carotid body chemoreceptors OIRD, we used whole-body plethysmography to evaluate hypoxic (HVR) and hypercapnic (HCVR) ventilatory responses including changes in frequency of breathing, tidal volume, minute ventilation and inspiratory drive, after intravenous injection of morphine (10 mg/kg) in sham-operated (SHAM) and in bilateral carotid sinus nerve transected (CSNX) Sprague-Dawley rats. In SHAM rats, morphine produced sustained respiratory depression (e.g., decreases in tidal volume, minute ventilation and inspiratory drive) and reduced the HVR and HCVR responses. Unexpectedly, morphine-induced suppression of HVR and HCVR were substantially greater in CSNX rats than in SHAM rats. This suggests that morphine did not compromise the function of the carotid body-chemoafferent complex and indeed, that the carotid body acts to defend against morphine-induced respiratory depression. These data are the first in vivo evidence that carotid body chemoreceptor afferents defend against rather than participate in OIRD in conscious rats. As such, drugs that stimulate ventilation by targeting primary glomus cells and/or chemoafferent terminals in the carotid bodies may help to alleviate OIRD.

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“…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.…”

mentioning

confidence: 87%

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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Antinociception Versus Serum Concentration Relationships Following Acute Administration of Intravenous Morphine in Male and Female Sprague‐dawley Rats: Differences Between the Tail Flick and Hot Plate Nociceptive Tests

Cited by 31 publications

References 25 publications

Lack of Adrenomedullin in the Central Nervous System Results in Apparently Paradoxical Alterations on Pain Sensitivity

Lack of Adrenomedullin in the Central Nervous System Results in Apparently Paradoxical Alterations on Pain Sensitivity

Bilateral carotid sinus nerve transection exacerbates morphine-induced respiratory depression

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

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