Serotonergic modulation of pain and analgesic responses: A study in rats with constitutionally altered serotonin transporters

Kesić, Maja; Tvrdeić, Ante; Kolarić, Darko; Stojković, Ranko; Čičin‐Šain, Lipa

doi:10.1002/ejp.574

Cited by 10 publications

(7 citation statements)

References 48 publications

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“…Moreover, healthy s-allele individuals were found to show reduced endogenous pain modulation (as assessed with the Conditioned Pain Modulation (CPM) paradigm, using a non-painful conditioning stimulus), which might render s-allele individuals more vulnerable to pain [ 24 ]. Furthermore, animal studies found heightened pain sensitivity in rats with low activity of the serotonin transporter [ 25 ], which converges with our findings of increased pain sensitivity in s-allele carriers. The lack of group differences in heat pain ratings does not refute the hypothesis of genotype-related differences in subjective pain experience because the intensity of supra-threshold heat stimuli was tailored to the individual heat pain threshold and thus, might have evened out inter-individual differences in subjective pain experience.…”

Section: Discussionsupporting

confidence: 91%

Relationship of 5-HTTLPR Polymorphism with Various Factors of Pain Processing: Subjective Experience, Motor Responsiveness and Catastrophizing

et al. 2016

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Although serotonin is known to play an important role in pain processing, the relationship between the polymorphism in 5-HTTLPR and pain processing is not well understood. To examine the relationship more comprehensively, various factors of pain processing having putative associations with 5-HT functioning were studied, namely the subjective pain experience (pain threshold, rating of experimental pain), catastrophizing about pain (Pain Catastrophizing Scale = PCS) and motor responsiveness (facial expression of pain). In 60 female and 67 male participants, heat pain stimuli were applied by a contact thermode to assess pain thresholds, supra-threshold ratings and a composite score of pain-relevant facial responses. Participants also completed the PCS and were grouped based on their 5-HTTLPR genotype (bi-allelic evaluation) into a group with s-allele carriers (ss, sl) and a second group without (ll). S-allele carriers proved to have lower pain thresholds and higher PCS scores. These two positive findings were unrelated to each other. No other difference between genotype groups became significant. In all analyses, “age” and “gender” were controlled for. In s-allele carriers the subjective pain experience and the tendency to catastrophize about pain was enhanced, suggesting that the s-allele might be a risk factor for the development and maintenance of pain. This risk factor seems to act via two independent routes, namely via the sensory processes of subjective pain experiences and via the booster effects of pain catastrophizing.

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Section: Discussionsupporting

confidence: 91%

Relationship of 5-HTTLPR Polymorphism with Various Factors of Pain Processing: Subjective Experience, Motor Responsiveness and Catastrophizing

et al. 2016

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“…29 Serotonin is also believed to play a crucial role in the pathobiology of depression 30 , and has been implicated in pain modulation. 31 Some authors have therefore suggested serotonergic signaling dysfunction as the underlying mechanism linking pain, sleep dysfunction, and depression in patients with chronic illness. 32 Other neurotransmitters including norepinephrine have also been suggested to contribute.…”

Section: Discussionmentioning

confidence: 99%

The pain–depression dyad and the association with sleep dysfunction in chronic rhinosinusitis

Cox

Ashby

Mace

et al. 2016

Int Forum Allergy Rhinol

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Background Depression, pain, and sleep disturbance is a symptom cluster often found in patients suffering from chronic illness, exerting a large impact on quality-of-life (QOL). A wealth of literature exists demonstrating a significant association between depression, pain, and sleep dysfunction in other chronic diseases. This relationship has not been described in patients with chronic rhinosinusitis (CRS). Methods Sixty-eight adult patients with CRS were prospectively enrolled. Patients at risk for depression were identified using the Patient Health Questionnaire-2 (PHQ-2) using a cutoff of 1 or greater. Pain experience was measured using the Brief Pain Inventory Short Form (BPI-SF) and the Short Form McGill Pain Questionnaire (SF-MPQ). Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Results Forty-seven patients were at risk for depression. Significant positive correlations were found between total PSQI scores and all pain measures (R=0.38–0.61, p≤0.05) and between total PSQI scores and PHQ-2 scores (R=0.46, p<0.05). For patients at risk for depression, significant, positive correlations were found between pain measures, the total PSQI score, and the three PSQI subdomains (sleep latency, sleep quality, and daytime dysfunction; R=0.31-0.61, p<0.05). The relationship between pain and sleep dysfunction scores was not seen in the absence of depression. Conclusions Depression, pain, and sleep dysfunction are inter-related in patients with CRS. In the absence of depression significant correlations between pain and sleep are not observed, suggesting that depression plays a key role in this interaction. Further research investigating the complex relationship between depression, pain, and sleep dysfunction in CRS is needed.

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“…As a consequence of genetic selection for platelet 5HT parameters, high-5HT and low-5HT rats have constitutionally different blood 5HT levels, but also show alterations in central 5HT homeostasis. Thus, animals from high-5HT subline not only have higher PSL but also higher biologically active 5HT levels in the platelet-free plasma pool [32], show higher 5HT turnover in the brain and higher KCl-induced elevation in extraneuronal 5HT [32,33], and respond differently to various behavioral challenges [32][33][34][35][36] than low-5HT animals. Therefore, animals from the high-5HT subline are considered to exhibit constitutional hyperactivity of the serotonin system compared to low-5HT rats.…”

Section: Introductionmentioning

confidence: 99%

Metabolic Disturbances in Rat Sublines with Constitutionally Altered Serotonin Homeostasis

Kesić

Baković

Stojković

et al. 2021

IJMS

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Central and peripheral serotonin (5HT) have opposing functions in the regulation of energy homeostasis. Both increasing 5HT signaling in the brain and decreasing 5HT signaling in the periphery have been proposed as potential treatments for obesity. This study investigates the relationship between constitutionally high or low 5HT activity and systemic net energy balance. Two sublines of rats with high and low whole-body 5HT tone, obtained by selective breeding for platelet 5HT parameters, were examined for fat accumulation in different white adipose tissue (WAT) depots, glucose/insulin tolerance, blood metabolic parameters, and expression of various metabolic genes. High-5HT animals, unlike their low-5HT counterparts, developed widespread intra-abdominal obesity associated with glucose and insulin intolerance, which worsened with age. They also had elevated blood glucose and lipid parameters but showed no significant changes in circulating leptin, resistin, and adipsin levels. Surprisingly, adiponectin levels were increased in plasma but reduced in the WAT of high-5HT rats. A limited number of metabolic genes belonging to different functional classes showed differential expression in WAT of high-5HT compared to low-5HT rats. Overall, a constitutive increase in 5HT tone is associated with a positive energy balance acting through subtle dysregulation of a broad spectrum of metabolic pathways.

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Serotonergic modulation of pain and analgesic responses: A study in rats with constitutionally altered serotonin transporters

Cited by 10 publications

References 48 publications

Relationship of 5-HTTLPR Polymorphism with Various Factors of Pain Processing: Subjective Experience, Motor Responsiveness and Catastrophizing

Relationship of 5-HTTLPR Polymorphism with Various Factors of Pain Processing: Subjective Experience, Motor Responsiveness and Catastrophizing

The pain–depression dyad and the association with sleep dysfunction in chronic rhinosinusitis

Metabolic Disturbances in Rat Sublines with Constitutionally Altered Serotonin Homeostasis

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