Monoamines as Drug Targets in Chronic Pain: Focusing on Neuropathic Pain

Bravo, Lidia; Llorca-Torralba, Meritxell; Berrocoso, Esther; Micó, Juan Antonio

doi:10.3389/fnins.2019.01268

Cited by 55 publications

(61 citation statements)

References 259 publications

(326 reference statements)

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“…Although sibutramine did not evoke significant c-Fos stimulatory responses in the hypothalamus, available preclinical data suggest that sibutramine confers appetite suppression by enhancing adrenoceptor activity in ARC and LH [ 58 ]. In our study, sibutramine-induced c-Fos signals were largely confined to the cortex, amygdala and thalamus, which is consistent with the antidepressant, anxiolytic and analgesic action of dual serotonin-noradrenaline reuptake inhibitors [ [59] , [60] , [61] ].…”

Section: Discussionsupporting

confidence: 87%

Whole-brain activation signatures of weight-lowering drugs

Hansen

Perens

Roostalu

et al. 2021

Molecular Metabolism

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Objective The development of effective anti-obesity therapeutics relies heavily on the ability to target specific brain homeostatic and hedonic mechanisms controlling body weight. To obtain further insight into neurocircuits recruited by anti-obesity drug treatment, the present study aimed to determine whole-brain activation signatures of six different weight-lowering drug classes. Methods Chow-fed C57BL/6J mice (n = 8 per group) received acute treatment with lorcaserin (7 mg/kg; i.p.), rimonabant (10 mg/kg; i.p.), bromocriptine (10 mg/kg; i.p.), sibutramine (10 mg/kg; p.o.), semaglutide (0.04 mg/kg; s.c.) or setmelanotide (4 mg/kg; s.c.). Brains were sampled two hours post-dosing and whole-brain neuronal activation patterns were analysed at single-cell resolution using c-Fos immunohistochemistry and automated quantitative three-dimensional (3D) imaging. Results The whole-brain analysis comprised 308 atlas-defined mouse brain areas. To enable fast and efficient data mining, a web-based 3D imaging data viewer was developed. All weight-lowering drugs demonstrated brain-wide responses with notable similarities in c-Fos expression signatures. Overlapping c-Fos responses were detected in discrete homeostatic and non-homeostatic feeding centres located in the dorsal vagal complex and hypothalamus with concurrent activation of several limbic structures as well as the dopaminergic system. Conclusions Whole-brain c-Fos expression signatures of various weight-lowering drug classes point to a discrete set of brain regions and neurocircuits which could represent key neuroanatomical targets for future anti-obesity therapeutics.

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Section: Discussionsupporting

confidence: 87%

Whole-brain activation signatures of weight-lowering drugs

Hansen

Perens

Roostalu

et al. 2021

Molecular Metabolism

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“…There is more than four decades of work on noradrenergic control of pain, with both peripheral and central mechanisms described (36,280). Yet this remains an area of dynamic research, particularly with respect to underlying circuitry, with ever-increasing new insights matched by a growing number of open questions.…”

Section: Noradrenergic Modulation Of Brain Circuits In Painmentioning

confidence: 99%

Cellular Circuits in the Brain and Their Modulation in Acute and Chronic Pain

Kuner

2021

Physiological Reviews

172

162

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Chronic, pathological pain remains a global health problem and a challenge to basic and clinical sciences. A major obstacle to preventing, treating or reverting chronic pain has been that the nature of neural circuits underlying the diverse components of the complex, multidimensional experience of pain is not well understood. Moreover, chronic pain involves diverse maladaptive plasticity processes, which have not been decoded mechanistically in terms of involvement of specific circuits and cause-effect relationships. This review aims to discuss recent advances in our understanding of circuit connectivity in the mammalian brain at the level of regional contributions and specific cell types in acute and chronic pain. A major focus is placed on functional dissection of sub-neocortical brain circuits using optogenetics, chemogenetics and imaging technological tools in rodent models with a view towards decoding sensory, affective and motivational-cognitive dimensions of pain. The review summarizes recent breakthroughs and insights on structure-function properties in nociceptive circuits and higher order sub-neocortical modulatory circuits involved in aversion, learning, reward and mood and their modulation by endogenous GABAergic inhibition, noradrenergic, cholinergic, dopaminergic, serotonergic and peptidergic pathways. The knowledge of neural circuits and their dynamic regulation via functional and structural plasticity will be beneficial towards designing and improving targeted therapies.

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“…It has been reported that opioid receptor agonists induce antinociception by interaction through cannabinoid (CB1) receptors [8]. Also opioids activity have been reported by inhibition of both NA and 5-HT reuptake [24]. However, an important contribution to opioid antinociception is the interaction capacity to open K + channels and inhibit the opening of Ca +2 channels, ions that play a very important role in the transmission of the pain signal to through Substance P, neurokinin1, calcitonine gene related peptide, glutamate [28].…”

Section: Discussionmentioning

confidence: 99%

NSAIDs and opioids antinociception in a thermal murine phasic pain

F¹,

Noriega²,

Sierralta³

et al. 2020

GSC Adv. Res. Rev.

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Pain is an unpleasant sensation that causes mild or severe physical discomfort, by which induces the use of analgesics which are basically of two types: opioids or NSAIDs. The objectives of the present study was to evaluate the antinociception activity induced by NSAIDs and opioids in a thermal model of animal pain, the tail flick assay, and to determine the effect of the MOR antagonist, naltrexone. Antinociception was assessed by the tail flick test using an digital algesiometer. The rank orden of potency was fentanyl > morphine > ibuprofen > tramadol > codeine > meloxicam > paracetamol and the antinociceptive ratio, compared with paracetamol, was between 460 for fentanyl and 1 for meloxicam. Pretreatment with the opioid receptor antagonist, naltrexone, 1 mg/kg i.p., significant reversed the antinociceptive effect of NSAIDs and opioids. The results obtained with naltrexone in this assay confirm the antagonism of this agent on opioids. However, the antagonism over NSAIDs is a new finding since that has not been previously reported. This study test that NSAIDs and opioids induce antinociceptive activity in a thermal murine phasic pain with the following rank orden of potency fentanyl > morphine > ibuprofen > tramadol > codeine > meloxicam > paracetamol. Although the mechanisms of action of these drugs are different, naltrexone, a MOR antagonist, blocked the effects of both agents, suggesting that inhibition of pain seem partially mediated by MOR with association to central mechanisms.

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Monoamines as Drug Targets in Chronic Pain: Focusing on Neuropathic Pain

Cited by 55 publications

References 259 publications

Whole-brain activation signatures of weight-lowering drugs

Whole-brain activation signatures of weight-lowering drugs

Cellular Circuits in the Brain and Their Modulation in Acute and Chronic Pain

NSAIDs and opioids antinociception in a thermal murine phasic pain

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