Behavioral model for diffuse noxious inhibitory controls (DNIC): potentiation by 5-hydroxytryptophan

Kraus, E; Besson, Jean‐Marie; Bars, D. Le

doi:10.1016/0006-8993(82)90384-5

Cited by 34 publications

(16 citation statements)

References 18 publications

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“…Pharmacological studies point towards the same conclusion [17],[54]. Resembling the work done on animal models, the presence of CPM in humans was initially investigated using the nociceptive flexion reflex (NFR).…”

Section: Discussionmentioning

confidence: 91%

“…Whereas administration of the serotonin (5-HT) precursor 5-hydroxytryptophan (5-HTP) led to a more potent inhibition, the 5-HT receptor antagonist cinanserin reversed this potentiation [17], [18]. A key player in 5-HT signaling is the 5-HT transporter (5-HTT), terminating the extracellular effects of 5-HT by sodium-dependent intracellular re-uptake [19].…”

Section: Introductionmentioning

confidence: 99%

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Conditioned Pain Modulation Is Associated with Common Polymorphisms in the Serotonin Transporter Gene

et al. 2011

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BackgroundVariation in the serotonin transporter (5-HTT) gene (SLC6A4) has been shown to influence a wide range of affective processes. Low 5-HTT gene-expression has also been suggested to increase the risk of chronic pain. Conditioned pain modulation (CPM) - i.e. ‘pain inhibits pain’ - is impaired in chronic pain states and, reciprocally, aberrations of CPM may predict the development of chronic pain. Therefore we hypothesized that a common variation in the SLC6A4 is associated with inter-individual variation in CPM. Forty-five healthy subjects recruited on the basis of tri-allelic 5-HTTLPR genotype, with inferred high or low 5-HTT-expression, were included in a double-blind study. A submaximal-effort tourniquet test was used to provide a standardized degree of conditioning ischemic pain. Individualized noxious heat and pressure pain thresholds (PPTs) were used as subjective test-modalities and the nociceptive flexion reflex (NFR) was used to provide an objective neurophysiological window into spinal processing.ResultsThe low, as compared to the high, 5-HTT-expressing group exhibited significantly reduced CPM-mediated pain inhibition for PPTs (p = 0.02) and heat-pain (p = 0.02). The CPM-mediated inhibition of the NFR, gauged by increases in NFR-threshold, did not differ significantly between groups (p = 0.75). Inhibition of PPTs and heat-pain were correlated (Spearman’s rho = 0.35, p = 0.02), whereas the NFR-threshold increase was not significantly correlated with degree of inhibition of these subjectively reported modalities.ConclusionsOur results demonstrate the involvement of the tri-allelic 5-HTTLPR genotype in explaining clinically relevant inter-individual differences in pain perception and regulation. Our results also illustrate that shifts in NFR-thresholds do not necessarily correlate to the modulation of experienced pain. We discuss various possible mechanisms underlying these findings and suggest a role of regulation of 5-HT receptors along the neuraxis as a function of differential 5-HTT-expression.

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Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Conditioned Pain Modulation Is Associated with Common Polymorphisms in the Serotonin Transporter Gene

et al. 2011

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“…For example, given the role that norepinephrine and serotonin play in descending modulation of pain (Basbaum & Fields, 1984), it is possible that bulbospinal norepinephrine and serotonin pathways play a role in endogenous analgesia produced during conditioned pain modulation. In several animal studies, complete or partial reduction in diffuse noxious inhibitory controls was demonstrated by administration of serotonin (Chitour et al, 1982; Kraus et al, 1982) and α-adrenergic (Gjerstad et al, 2000; Wen et al, 2010) receptor antagonists, respectively. Additionally, complete blockade has been accomplished by opioid and adrenergic receptor antagonism (Wen et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Reduction of conditioned pain modulation in humans by naltrexone: an exploratory study of the effects of pain catastrophizing

et al. 2012

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The current study tested the hypothesis that conditioned pain modulation is mediated by the release of endogenous opioids with a placebo-controlled (sugar pill) study of naltrexone (50 mg) in 33 healthy volunteers over two counter-balanced sessions. Pain modulation consisted of rating of heat pain (palm) during concurrent cold water immersion (foot). Compared to baseline heat pain ratings, concurrent foot immersion lowered pain intensity ratings, which suggests an inhibitory effect, was reduced with naltrexone, suggesting at least partial dependence of inhibition on endogenous opioids. An exploratory analysis revealed that individual differences in catastrophizing moderated the effects of naltrexone; endogenous opioid blockade abolished modulation in subjects lower in catastrophizing while modulation was unaffected by naltrexone among high catastrophizers. The results suggest a role of endogenous opioids in endogenous analgesia, but hint that multiple systems might contribute to conditioned pain modulation, and that these systems might be differentially activated as a function of individual differences in responses to pain.

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“…The presence of poor inhibitory controls preoperatively also appears to predict increased vulnerability to chronic pain development after surgery. Certainly the presence of sensitization (i.e., increase in pain sensitivity) with the DNIC/CPM paradigm preoperatively should lead the anesthesiologist take his task of perioperative antinociceptive management particularly seriously, and to additionally consider instituting antihyperalgesic measures or interventions designed to improve descending inhibitory controls, e.g., via drugs affecting monoaminergic function such as tricyclic antidepressants (139,140).…”

Section: Implications For Clinical Practice and Future Researchmentioning

confidence: 99%

Chronic Pain and Surgery: A Review of New Insights from Sensory Testing

Wilder–Smith

2011

Journal of Pain & Palliative Care Pharmacotherapy

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Chronic pain is increasingly recognized as an undesirable outcome after surgery. Predicting risk of postoperative chronic pain, as well as chronic pain prevention or treatment, requires understanding of the processes underlying its development. Quantitative sensory testing research over the last decade has made it possible to start understanding the alterations in central pain processing associated with chronic pain and its development. Chronic pain syndromes are typically characterized by a pronociceptive state of pain processing, e.g., generalized hyperalgesia as a sign of supraspinal central sensitization and poor inhibitory or even facilitatory descending modulation. In the perioperative context, development and progression of chronic pain are accompanied by signs congruent with a shift towards a pronociceptive state. Preoperatively, hyperalgesia and poor descending inhibitory modulation appear to increase the risk of subsequent chronic pain. Postoperatively, abnormal persistence and spread of hyperalgesia, compatible with rostral neuraxial spread of central sensitization, are increasingly linked to the development and progression of chronic pain. These findings, which need further confirmation, suggest that perioperative quantitative sensory testing of pain sensitivity and pain modulation has the potential to become a valuable clinical tool for assessing risk of chronic pain development and for managing its prevention and treatment.

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Behavioral model for diffuse noxious inhibitory controls (DNIC): potentiation by 5-hydroxytryptophan

Cited by 34 publications

References 18 publications

Conditioned Pain Modulation Is Associated with Common Polymorphisms in the Serotonin Transporter Gene

Conditioned Pain Modulation Is Associated with Common Polymorphisms in the Serotonin Transporter Gene

Reduction of conditioned pain modulation in humans by naltrexone: an exploratory study of the effects of pain catastrophizing

Chronic Pain and Surgery: A Review of New Insights from Sensory Testing

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