scholarly journals The Role of Descending Pain Modulation in Chronic Primary Pain: Potential Application of Drugs Targeting Serotonergic System

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Zhuo-Ying Tao ◽  
Pei-Xing Wang ◽  
Si-Qi Wei ◽  
Richard J. Traub ◽  
Jin-Feng Li ◽  
...  
Keyword(s):  
Potential Application ◽  
Pain Modulation ◽  
Serotonergic System ◽  
Intractable Pain ◽  
Cost Of Health Care ◽  
Antinociceptive Effects ◽  
Regulation Mechanisms ◽  
Specific Tissue ◽  
Descending Pain Modulation

Chronic primary pain (CPP) is a group of diseases with long-term pain and functional disorders but without structural or specific tissue pathologies. CPP is becoming a serious health problem in clinical practice due to the unknown cause of intractable pain and high cost of health care yet has not been satisfactorily addressed. During the past decades, a significant role for the descending pain modulation and alterations due to specific diseases of CPP has been emphasized. It has been widely established that central sensitization and alterations in neuroplasticity induced by the enhancement of descending pain facilitation and/or the impairment of descending pain inhibition can explain many chronic pain states including CPP. The descending serotonergic neurons in the raphe nuclei target receptors along the descending pain circuits and exert either pro- or antinociceptive effects in different pain conditions. In this review, we summarize the possible underlying descending pain regulation mechanisms in CPP and the role of serotonin, thus providing evidence for potential application of analgesic medications based on the serotonergic system in CPP patients.

Endogenous opioids in placebo-induced analgesia

2018 ◽  
Author(s):  
Véronique A. Taylor ◽  
Pierre Rainville
Keyword(s):  
Pain Modulation ◽  
Endogenous Opioids ◽  
Anterior Cingulate ◽  
Placebo Analgesia ◽  
Psychological Determinants ◽  
Post Operative Pain ◽  
Conditioned Learning ◽  
Descending Pain Modulation ◽  
Pharmacological Manipulations

Placebos achieve scientifically proven pain-relieving effects yet are inactive substances for the treatment of pain. Levine, Gordon, and Fields were the first to demonstrate the role of endogenous opioids in placebo-induced analgesia during dental post-operative pain. Several studies using pharmacological manipulations and/or neuroimaging techniques confirmed their findings that placebo analgesia is reversible by naloxone, and also identified brain pathways involved in opioidergic neurotransmission during placebo analgesia (prefrontal regions rich in opioid receptors such as the anterior cingulate cortex, presumably initiating descending pain modulation through downstream projections to the brainstem). Fifty years of research in pharmacology and neurobiology have contributed to the identification of physical as well as psychological determinants of placebo analgesia. Expectations of pain relief are maintained by conditioned learning and reward-related processes, reflected by interactions between different neurotransmitters (opioids, dopamine, endocannabinoids) in a variety of brain circuits related to executive/cognitive processes as well as affect and reward.

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

2015 ◽  
Vol 53 (3) ◽  
pp. 1706-1717 ◽  
Author(s):  
Dabna H. Tomim ◽  
Felipe M. Pontarolla ◽  
Jessica F. Bertolini ◽  
Mauricio Arase ◽  
Glaucia Tobaldini ◽  
...  
Keyword(s):  
Sleep Deprivation ◽  
Paradoxical Sleep ◽  
Pain Modulation ◽  
Paradoxical Sleep Deprivation ◽  
Descending Pain Modulation

A novel clinical applicable bed-side tool for assessing conditioning pain modulation: proof-of-concept

2020 ◽  
Vol 20 (4) ◽  
pp. 801-807
Author(s):  
Lars Arendt-Nielsen ◽  
Jesper Bie Larsen ◽  
Stine Rasmussen ◽  
Malene Krogh ◽  
Laura Borg ◽  
...  
Keyword(s):  
Pain Modulation ◽  
Clinical Settings ◽  
Proof Of Concept ◽  
Finger Nail ◽  
Tonic Stimulus ◽  
Pressure Pain Thresholds ◽  
Custom Made ◽  
The Individual ◽  
Descending Pain Modulation ◽  
Finger Pressure

AbstractBackground and aimsIn recent years, focus on assessing descending pain modulation or conditioning pain modulation (CPM) has emerged in patients with chronic pain. This requires reliable and simple to use bed-side tools to be applied in the clinic. The aim of the present pilot study was to develop and provide proof-of-concept of a simple clinically applicable bed-side tool for assessing CPM.MethodsA group of 26 healthy volunteers participated in the experiment. Pressure pain thresholds (PPT) were assessed as test stimuli from the lower leg before, during and 5 min after delivering the conditioning tonic painful pressure stimulation. The tonic stimulus was delivered for 2 min by a custom-made spring-loaded finger pressure device applying a fixed pressure (2.2 kg) to the index finger nail. The pain intensity provoked by the tonic stimulus was continuously recorded on a 0–10 cm Visual Analog Scale (VAS).ResultsThe median tonic pain stimulus intensity was 6.7 cm (interquartile range: 4.6–8.4 cm) on the 10 cm VAS. The mean PPT increased significantly (P = 0.034) by 55 ± 126 kPa from 518 ± 173 kPa before to 573 ± 228 kPa during conditioning stimulation. When analyzing the individual CPM responses (increases in PPT), a distribution of positive and negative CPM responders was observed with 69% of the individuals classified as positive CPM responders (increased PPTs = anti-nociceptive) and the rest as negative CPM responders (no or decreased PPTs = Pro-nociceptive). This particular responder distribution explains the large variation in the averaged CPM responses observed in many CPM studies. The strongest positive CPM response was an increase of 418 kPa and the strongest negative CPM response was a decrease of 140 kPa.ConclusionsThe present newly developed conditioning pain stimulator provides a simple, applicable tool for routine CPM assessment in clinical practice. Further, reporting averaged CPM effects should be replaced by categorizing volunteers/patients into anti-nociceptive and pro-nociceptive CPM groups.ImplicationsThe finger pressure device provided moderate-to-high pain intensities and was useful for inducing conditioning stimuli. Therefore, the finger pressure device could be a useful bed-side method for measuring CPM in clinical settings with limited time available. Future bed-side studies involving patient populations are warranted to determine the usefulness of the method.

scholarly journals Role of interleukins in the pathogenesis of pulmonary fibrosis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yi Xin She ◽  
Qing Yang Yu ◽  
Xiao Xiao Tang
Keyword(s):  
Pulmonary Fibrosis ◽  
Therapeutic Strategy ◽  
Future Directions ◽  
Regulation Mechanisms ◽  
Underlying Mechanisms ◽  
Multiple Cells ◽  
The Relationship

AbstractInterleukins, a group of cytokines participating in inflammation and immune response, are proved to be involved in the formation and development of pulmonary fibrosis. In this article, we reviewed the relationship between interleukins and pulmonary fibrosis from the clinical, animal, as well as cellular levels, and discussed the underlying mechanisms in vivo and in vitro. Despite the effects of interleukin-targeted treatment on experimental pulmonary fibrosis, clinical applications are lacking and unsatisfactory. We conclude that intervening in one type of interleukins with similar functions in IPF may not be enough to stop the development of fibrosis as it involves a complex network of regulation mechanisms. Intervening interleukins combined with other existing therapy or targeting interleukins affecting multiple cells/with different functions at the same time may be one of the future directions. Furthermore, the intervention time is critical as some interleukins play different roles at different stages. Further elucidation on these aspects would provide new perspectives on both the pathogenesis mechanism, as well as the therapeutic strategy and drug development.

scholarly journals Role of Neuroglobin in the Neuroprotective Actions of Estradiol and Estrogenic Compounds

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1907
Author(s):  
George E. Barreto ◽  
Andrew J. McGovern ◽  
Luis M. Garcia-Segura
Keyword(s):  
Sex Differences ◽  
Signaling Pathways ◽  
Glial Cell ◽  
Potential Application ◽  
Neurological Diseases ◽  
Brain Pathology ◽  
Synthetic Steroids ◽  
Neuroprotective Actions ◽  
Estrogenic Regulation

Estradiol exerts neuroprotective actions that are mediated by the regulation of a variety of signaling pathways and homeostatic molecules. Among these is neuroglobin, which is upregulated by estradiol and translocated to the mitochondria to sustain neuronal and glial cell adaptation to injury. In this paper, we will discuss the role of neuroglobin in the neuroprotective mechanisms elicited by estradiol acting on neurons, astrocytes and microglia. We will also consider the role of neuroglobin in the neuroprotective actions of clinically relevant synthetic steroids, such as tibolone. Finally, the possible contribution of the estrogenic regulation of neuroglobin to the generation of sex differences in brain pathology and the potential application of neuroglobin as therapy against neurological diseases will be examined.

The role of tryptophan in hepatic encephalopathy

1993 ◽  
Vol 5 (4) ◽  
pp. 71-75
Author(s):  
C. Aaldijk ◽  
W.W. Van Den Broek ◽  
R.C. Van Der Mast
Keyword(s):  
Hepatic Encephalopathy ◽  
Clinical Picture ◽  
Serotonergic System ◽  
Pathogenetic Mechanisms ◽  
Research Findings ◽  
Glutamine Synthesis ◽  
The Brain ◽  
Tryptophan Uptake

SummaryIn this review the most important hypotheses for the occurrence of the clinical picture of hepatic encephalopathy are discussed. As possible pathogenetic mechanisms are raised: dysfunction of the serotonergic system due to an increased tryptophan uptake in the brain, an elevated intracerebral ammoniac concentration and glutamine synthesis, and a heightened intracerebral GABA-activity.The dysregulation of the serotonergic system as a consequence of the increased intracerebral tryptophan uptake is described as one of the most important pathogenetic mechanisms. The elevated intracerebral ammoniac concentration and the elevated intracerebral glutamine synthesis play in this a facilitating role. The similarity in symptomatology of the clinical picture of HE and the serotonergic syndrome support this hypothesis. Due to contradictory research findings the role of the GABA-ergic system and the occurrence of HE remains unclear.

The role of endocannabinoids in pain modulation

2013 ◽  
Vol 27 (1) ◽  
pp. 64-80 ◽  
Author(s):  
Panagiotis Zogopoulos ◽  
Ioanna Vasileiou ◽  
Efstratios Patsouris ◽  
Stamatios E. Theocharis
Keyword(s):  
Pain Modulation

The antinociceptive effects of magnesium sulfate and MK-801 in visceral inflammatory pain model: The role of NO/cGMP/K+ATP pathway

2015 ◽  
Vol 53 (11) ◽  
pp. 1621-1627 ◽  
Author(s):  
Sonja Vuckovic ◽  
Dragana Srebro ◽  
Katarina Savic Vujovic ◽  
Milica Prostran
Keyword(s):  
Magnesium Sulfate ◽  
Inflammatory Pain ◽  
Pain Model ◽  
Mk 801 ◽  
Antinociceptive Effects

scholarly journals EGCG Prevents the Loss of Pontine Noradrenergic Neurons Induced by Diabetes: A Role in Diabetic Neuropathic Pain

2012 ◽  
Vol 18 (S5) ◽  
pp. 5-6 ◽  
Author(s):  
Carla Morgado ◽  
João Silva ◽  
André Miranda ◽  
Patrícia Pereira-Terra ◽  
Diogo Raposo ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Diabetic Rats ◽  
Pain Modulation ◽  
Diabetic Patients ◽  
Spontaneous Pain ◽  
Noradrenergic Neurons ◽  
Diabetic Neuropathic Pain ◽  
Descending Pain Modulation ◽  
Pain Responses

Diabetes is a major health problem with an alarming increasing prevalence, and is the most frequent cause of neuropathy worldwide. Neuropathy affects 50–60% of diabetic patients, being a major life-quality impairment for a quarter of these patients. Diabetic neuropathic pain (DNP) is characterized by spontaneous pain, mechanical hyperalgesia and tactile allodynia and is accompanied by functional and neurochemical changes at the peripheral nerves, spinal cord and supraspinal pain control areas. Regarding the effects of diabetic neuropathy in the central somatossensory system, it was shown that streptozotocin (STZ)-diabetic rats present spontaneous hyperactivity and hyperexcitability of spinal nociceptive neurons, which may be subserving the exacerbated pain responses. The spinal functional changes and pain may be due to increased peripheral input(2), changes in spinal nociceptive modulatory mechanisms and altered supraspinal descending pain modulation. Noradrenergic descending pain modulation seems to be impaired since STZ-diabetic rats present decreased numbers of noradrenergic neurons at the A5 and A7 pontine cell groups, along with lower levels of noradrenaline at the spinal cord and higher behavioral responses to pain. This is consistent with the strong noradrenergic projection from A5 and A7 neurons to the spinal dorsal horn and the modulation of nociceptive transmission by local release of noradrenaline. The mechanisms underlying the decrease in noradrenergic neurons in the brainstem during diabetes remain unclear. Our recent findings that diabetes induces oxidative stress damage in neurons from those areas, lead us to hypothesize that it may contribute to their loss. Thereafter, with the present study we aimed to evaluate the effects of Epigallocathechin Gallate (EGCG), a potent antioxidant present in green tea, on spinal noradrenaline levels, on A5 and A7 noradrenergic neurons and on behavioral pain responses of STZ-diabetic rats.

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