Publications by authors named "Glaucia Tobaldini"

10 Publications

  • Page 1 of 1

Short- and Long-Term Effects of Dietary Supplementation with Fish Oil on Inflammatory Pain in Rats.

J Am Coll Nutr 2021 Jun 22:1-9. Epub 2021 Jun 22.

Department of Physiology, Division of Biological Sciences, Federal University of Parana, Curitiba, Parana, Brazil.

Introduction: Dietary supplementation with fish oil is promising as a complementary therapy for inflammatory pain. However, further studies are needed to support its therapeutic potential. For example, the antinociceptive effect of fish oil is widely suggested to be dependent on decreased prostaglandin E (PGE) synthesis, but no previous study has investigated if it affects PGE-induced nociceptive response. Similarly, beneficial long-term effects on inflammatory response are related to early exposure to fish oil, however, whether these effects include decreased inflammatory pain throughout life is not known.

Objective: The aim of this study was to investigate the short- and long-term effects of fish oil on inflammatory pain.

Methods: Dietary fish oil supplementation was performed through two protocols: in adult rats, during 20 days, or in dams, during pregnancy and lactation, with tests performed in adult offspring. The hyperalgesic response induced by carrageenan and its final mediators PGE and norepinephrine was used to model inflammatory pain.

Results: The findings demonstrated for the first time that dietary fish oil (1) decreases the hyperalgesia induced by carrageenan; (2) but not that induced by its final mediator PGE and norepinephrine; (3) increase omega-3 polyunsaturated fatty acids in peripheral neural tissue; and (4) attenuates inflammatory pain in individuals exposed to fish oil during pre-natal life and lactation.

Conclusion: Together, these findings support that fish oil decreases inflammatory pain either when consumed during adult life or during prenatal development. Future studies should confirm the therapeutic potential of fish oil in humans, which is essential for the development of public policies to encourage a fish oil richer diet.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07315724.2021.1911006DOI Listing
June 2021

Pain impairs consolidation, but not acquisition or retrieval of a declarative memory.

Behav Pharmacol 2020 12;31(8):707-715

Laboratory of Neurophysiology, Department of Physiology, Division of Biological Sciences, Federal University of Parana, Curitiba, Parana 81530-000, Brazil.

Among the physical conditions that impair memory performance, pain is one of the most prevalent. However, the mechanisms by which pain impairs memory are largely unknown. In this study, we asked whether pain affects memory acquisition, consolidation and retrieval as well as whether memory impairment depends on pain intensity. Wistar rats received a hind paw injection of formalin (1%) at different phases of object recognition test. The injection of formalin after training but not before training or testing impaired object recognition memory. We concluded that pain impairs the consolidation but not acquisition or retrieval of object recognition memory, which is a subtype of declarative memory. Morphine, at a dose that did not affect object recognition memory in control rats, drastically reduced formalin-induced nociceptive behavior without reversing memory impairment. A lower dose of formalin (0.25%) induced less nociceptive behavior, but similar memory impairment. There is no statistical correlation between the intensity of nociceptive response and the performance in object recognition test. However, when formalin-induced nociceptive response was blocked by a local anesthetic, memory impairment was prevented. These findings suggest that pain-induced impairment in the consolidation of object recognition memory does not directly depend on the intensity of nociceptive activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/FBP.0000000000000576DOI Listing
December 2020

Pain and stress: functional evidence that supra-spinal mechanisms involved in pain-induced analgesia mediate stress-induced analgesia.

Behav Pharmacol 2020 04;31(2&3):159-167

Department of Physiology, Division of Biological Sciences, Federal University of Parana, Curitiba.

Analgesia induced by stressful and painful stimuli is an adaptive response during life-threatening situations. There is no evidence linking the mechanisms underlying them, while the former depends on the activation of stress-related brain pathways, the second depends on opioidergic mechanisms in the nucleus accumbens and on nicotinic cholinergic mechanisms in the rostral ventromedial medulla. In this study, we hypothesized that stress-induced analgesia is also dependent on opioidergic mechanisms in the nucleus accumbens and on nicotinic cholinergic mechanisms in the rostral ventromedial medulla. We used immobilization, a classical procedure to induce acute stress, and evaluated its ability to decrease the nociceptive responses induced either by carrageenan or by formalin in rats. Immobilization stress significantly decreased either carrageenan-induced hyperalgesia or formalin-induced tonic nociception in a time-dependent manner. This stress-induced analgesia is similar to pain-induced analgesia, as revealed by contrasting the antinociceptive effect induced by immobilization and by a forepaw injection of capsaicin. The administration of a µ-opioid receptor antagonist (CTOP, 0.5 µg) into the nucleus accumbens, as well as that of a nicotinic cholinergic receptor antagonist (mecamylamine, 0.6 µg) into the rostral ventromedial medulla, blocked immobilization stress-induced analgesia in both pain models. These results demonstrate that supraspinal mechanisms which are known to mediate pain-induced analgesia also mediate stress-induced analgesia. Therefore both forms of analgesia have overlapping mechanisms, probably recruited in response to the perception of danger.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/FBP.0000000000000529DOI Listing
April 2020

Pain chronification and chronic pain impair a defensive behavior, but not the ability of acute pain to facilitate it, through the activation of an endogenous analgesia circuit.

Behav Neurosci 2018 Dec 4;132(6):614-623. Epub 2018 Oct 4.

Department of Physiology, Piracicaba Dental School, State University of Campinas.

The endogenous ability to decrease pain perception during life-threatening situations is crucial to the prevention of recuperative behaviors and to leave the subject free to engage in appropriated defensive responses. We have previously shown that acute pain activates the ascending nociceptive control-an endogenous analgesia circuit dependent on opioid mechanisms within nucleus accumbens-to facilitate the tonic immobility response, an innate defensive behavior. Now we asked whether chronic pain and pain chronification impairs either the tonic immobility response or the ability of acute pain to facilitate it by activating the ascending nociceptive control. We found a significant decrease in the duration of the tonic immobility response in rats during the induction and maintenance phases of the persistent mechanical hyperalgesia. This finding suggests that chronic pain and its development impair defensive responses. However, during the induction and maintenance phases of persistent hyperalgesia, the ascending nociceptive control activation, by a forepaw capsaicin injection, increased the tonic immobility response, an effect prevented by the blockade of μ-opioid receptors within nucleus accumbens. This finding suggests that pain chronification and chronic pain do not prevent the ability of acute pain to facilitate the defensive behavior of tonic immobility by activating the ascending nociceptive control. Therefore, although chronic pain states decrease the ability to engage in a defensive behavior, they may not prevent the expression of defensive behaviors during life-threatening situations accompanied by acute pain. The biological purpose of such a mechanism may be to increase the chances of survival of a wounded subject exposed to acute pain in a novel life-threatening situation. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1037/bne0000255DOI Listing
December 2018

Chronic sleep restriction increases pain sensitivity over time in a periaqueductal gray and nucleus accumbens dependent manner.

Neuropharmacology 2018 09 19;139:52-60. Epub 2018 Jun 19.

Neurophysiology Laboratory, Department of Physiology, Division of Biological Sciences, Federal University of Parana, Curitiba, Parana, Brazil. Electronic address:

Painful conditions and sleep disturbances are major public health problems worldwide and one directly affects the other. Sleep loss increases pain prevalence and severity; while pain disturbs sleep. However, the underlying mechanisms are largely unknown. Here we asked whether chronic sleep restriction for 6 h daily progressively increases pain sensitivity and if this increase is reversed after two days of free sleep. Also, whether the pronociceptive effect of chronic sleep restriction depends on the periaqueductal grey and on the nucleus accumbens, two key regions involved in the modulation of pain and sleep-wake cycle. We showed that sleep restriction induces a pronociceptive effect characterized by a significant decrease in the mechanical paw withdrawal threshold in rats. Such effect increases progressively from day 3 to day 12 remaining stable thereafter until day 26. Two consecutive days of free sleep were not enough to reverse the effect, not even to attenuate it. This pronociceptive effect depends on the periaqueductal grey and on the nucleus accumbens, since it was prevented by their excitotoxic lesion. Complementarily, chronic sleep restriction significantly increased c-Fos protein expression within the periaqueductal grey and the nucleus accumbens and this correlates with the intensity of the pronociceptive effect, suggesting that the greater the neural activity in this regions, the greater the effect. These findings may contribute not only to understand why painful conditions are more prevalent and severe among people who sleep poorly, but also to develop therapeutic strategies to prevent this, increasing the effectiveness of pain management in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuropharm.2018.06.022DOI Listing
September 2018

Pain Inhibits Pain: an Ascending-Descending Pain Modulation Pathway Linking Mesolimbic and Classical Descending Mechanisms.

Mol Neurobiol 2019 Feb 1;56(2):1000-1013. Epub 2018 Jun 1.

Department of Physiology, Division of Biological Sciences, Federal University of Parana, Curitiba, Parana, Brazil.

The ability to modulate pain perception is as critical to survival as pain itself. The most known pain modulation pathway is the PAG-RVM (periaqueductal gray-rostral ventromedial medulla) descending system. In this study, we hypothesized that it is functionally linked to the ascending nociceptive control, which is a form of pain-induced analgesia dependent on mesolimbic mechanisms. To test this hypothesis, we used a pharmacological approach, in which the antinociception induced by noxious stimulation (forepaw injection of capsaicin) was detected in a standard rat model of inflammatory pain (hindpaw injection of carrageenan). This antinociception was blocked by interventions known to block the ascending nociceptive control-mediated analgesia: the blockade of μ-opioid (Cys,Tyr,Orn,Penamide (CTOP) 0.5 μg) or of dopamine (SCH23390 1.8 μg and raclopride 5 μg) receptors within the NAc (nucleus accumbens) and that of cholinergic nicotinic receptors (mecamylamine 0.6 μg) within the RVM. The antinociception was also blocked by standard interventions known to block mechanisms of descending inhibition within either the PAG or the RVM: local acute neuronal blockade (lidocaine 2%), blockade of μ-opioid receptors (CTOP 0.5 μg), or activation of GABA receptors (muscimol 10 ng). Consistently, interventions that are known to block spinal mechanisms of descending inhibition also blocked antinociception: lesion of dorsolateral funiculus and the spinal blockade of serotonergic (WAY100135 46 μg or tropisetron 10 μg) or adrenergic (idazoxan, 50 μg) receptors. Neuronal activity indirectly estimated by c-Fos expression within the NAc, PAG, and RVM supports behavioral observations. Therefore, this study provides functional data indicating that noxious stimulation triggers an ascending-descending pain modulation pathway linking the mesolimbic system to the PAG-RVM descending system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12035-018-1116-7DOI Listing
February 2019

Dopaminergic mechanisms in periaqueductal gray-mediated antinociception.

Behav Pharmacol 2018 04;29(2 and 3-Spec Issue):225-233

As important as perceiving pain is the ability to modulate this perception in some contextual salient situations. The periaqueductal gray (PAG) is perhaps the most important site of endogenous pain modulation; however, little is known about dopaminergic mechanisms underlying PAG-mediated antinociception. In this study, we used a pharmacological approach to evaluate this subject. We found that µ-opioid receptor-induced antinociception (DAMGO, 0.3 μg) from PAG was blocked by the coadministration of either D1-like or D2-like dopaminergic antagonists (SCH23390, 2, 4, and 6 μg or raclopride, 2 and 4 μg, respectively) both in the tail-flick and in the mechanical paw-withdrawal test. A selective D2-like receptor agonist (piribedil, 6 and 12 μg into the PAG) induced antinociception in the mechanical paw-withdrawal test, but not in the tail-flick test. This effect was blocked by the coadministration of its selective antagonist (raclopride 4 μg), as well as by either a GABAA agonist (muscimol, 0.1 μg) or an opioid receptor antagonist (naloxone, 0.5 μg). A selective D1-like receptor agonist (SKF38393, 1, 5, and 10 μg into the PAG) induced a poor and transient antinociceptive effect, but when combined with piribedil, a potentiated antinociceptive effect emerged. None of these treatments affected locomotion in the open-field test. These findings suggest that µ-opioid antinociception from the PAG depends on dopamine acting on both D1-like and D2-like receptors. Selective activation of PAG D2-like receptors induces antinociception mediated by supraspinal mechanisms dependent on inhibition of GABAA and activation of opioid neurotransmission.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/FBP.0000000000000346DOI Listing
April 2018

Nucleus accumbens mediates the pronociceptive effect of sleep deprivation: the role of adenosine A2A and dopamine D2 receptors.

Pain 2018 01;159(1):75-84

Department of Physiology, Division of Biological Sciences, Federal University of Parana, Curitiba, Parana, Brazil.

Sleep disorders increase pain sensitivity and the risk of developing painful conditions; however, the underlying mechanisms are poorly understood. It has been suggested that nucleus accumbens (NAc) influences sleep-wake cycle by means of a balance between adenosine activity at A2A receptors and dopamine activity at D2 receptors. Because the NAc also plays an important role in pain modulation, we hypothesized that the NAc and its A2A and D2 receptors mediate the pronociceptive effect of rapid eye movement (REM) sleep deprivation (SD). We found that 24 hours of REM-SD induced an intense pronociceptive effect in Wistar rats, which decreases progressively over a sleep rebound period. Although the level of fecal glucocorticoid metabolites increased with SD within group, it did not differ between sleep-deprived group and control group, indicating a stress response with similar magnitude between groups. The pronociceptive effect of REM-SD was prevented by excitotoxic lesion (N-Methyl-D-aspartate, 5.5 μg) of NAc and reverted by its acute blockade (Qx-314, 2%). The administration of an A2A receptor antagonist (SCH-58261, 7 ng) or a D2 receptor agonist (piribedil, 6 μg) into the NAc increased home cage activity and blocked the pronociceptive effect of REM-SD. Complementarily, an A2A receptor agonist (CGS-21680, 24 ng) impaired the reversal of the pronociceptive effect and decreased home cage activity, as it did a D2 receptor antagonist (raclopride, 5 μg). Rapid eye movement SD did not affect the expression of c-Fos protein in NAc. These data suggest that SD increases pain by increasing NAc adenosinergic A2A activity and by decreasing NAc dopaminergic D2 activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/j.pain.0000000000001066DOI Listing
January 2018

The Pronociceptive Effect of Paradoxical Sleep Deprivation in Rats: Evidence for a Role of Descending Pain Modulation Mechanisms.

Mol Neurobiol 2016 Apr 24;53(3):1706-1717. Epub 2015 Feb 24.

Department of Physiology, Division of Biological Sciences, Federal University of Parana, Curitiba, Parana, Brazil.

The mechanisms underlying the pronociceptive effect of paradoxical sleep deprivation (PSD) are not known. In this study, we asked whether PSD increases tonic nociception in the formalin test, decreases the antinociceptive effect of morphine administered into the periaqueductal gray matter (PAG), and disrupts endogenous descending pain modulation. PSD for either 24 or 48 h significantly increased formalin-induced nociception and decreased mechanical nociceptive paw withdrawal threshold. The maximal antinociceptive effect induced by morphine (0.9-9 nmol, intra-PAG) was significantly decreased by PSD. The administration of a low dose of the GABAA receptor antagonist, bicuculline (30-300 pmol, intra-PAG), decreased nociception in control rats, but not in paradoxical-sleep-deprived ones. Furthermore, the administration of the cholecystokinin (CCK) 2 receptor antagonist, YM022 (0.5-2 pmol) in the rostral ventral medulla (RVM), decreased nociception in paradoxical-sleep-deprived rats but not in control ones. While a dose of the CCK 2 receptor agonist, CCK-8 (8-24 pmol intra-RVM), increased nociception in control rats, but not in paradoxical-sleep-deprived ones. In addition, the injection of lidocaine (QX-314, 2%, intra-RVM) decreased nociception in sleep-deprived rats, but not in control rats, while the lesion of the dorsolateral funiculus prevented the pronociceptive effect of PSD. Finally, PSD significantly increased c-Fos expression in the RVM. Therefore, PSD increases pain independently of its duration or of the characteristic of the nociceptive stimulus and decreases morphine analgesia at the PAG. PSD appears to increase pain by decreasing descending pain inhibitory activity and by increasing descending pain facilitatory activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12035-014-9059-0DOI Listing
April 2016

Ascending nociceptive control contributes to the antinociceptive effect of acupuncture in a rat model of acute pain.

J Pain 2014 Apr 9;15(4):422-34. Epub 2014 Jan 9.

Department of Physiology, Division of Biological Sciences, Federal University of Parana, Curitiba, Parana, Brazil. Electronic address:

Unlabelled: Acupuncture-induced analgesia depends on the activation of endogenous pain modulation pathways. In this study, we asked whether ascending nociceptive control (ANC), a form of pain-induced analgesia, contributes to the antinociceptive effect of acupuncture. To answer this question, we tested the ability of procedures that block ANC-induced analgesia, at peripheral, spinal, nucleus accumbens and rostral ventral medulla levels, to block acupuncture-induced analgesia. Acupuncture at ST36 (Zusanli), a widely used acupoint located in the hind limb, induced potent heterosegmental antinociception in the orofacial formalin test. The magnitude of this antinociceptive effect was similar to that induced by an intraplantar injection of capsaicin, a procedure classically used to activate ANC. The antinociceptive effect of acupuncture was blocked by sciatic C-fibers depletion (1% perineural capsaicin), spinal administration of a μ-opioid (Cys2,Tyr3,Orn5,Pen7amide, .2 μg) or of a GABAA (bicuculline, .3 μg) receptor antagonist, intra-nucleus accumbens administration of a μ-opioid receptor antagonist (Cys2,Tyr3,Orn5,Pen7amide, 1 μg), or intrarostral ventral medulla administration of a nicotinic acetylcholine receptor antagonist (mecamylamine, .6 μg). In addition, acupuncture at ST36 and/or upper lip formalin induced c-Fos expression in the nucleus accumbens and in rostral ventral medulla. On the basis of these results, we propose that ANC contributes to the antinociceptive effect of acupuncture.

Perspective: This article presents a novel mechanism of acupuncture analgesia, contributing to the understanding of its scientific basis. Because ANC is a pain modulation pathway activated by peripheral noxious stimulation that ascends to supraspinal regions, it could be the link between acupoint stimulation and the central mechanisms underlying acupuncture analgesia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpain.2013.12.008DOI Listing
April 2014
-->