Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0184567 (acute pain)
 3,962 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary headache syndromes, such as cluster headache and migraine, are widely described as vascular headaches, although considerable clinical evidence suggests that both are primarily driven from the brain. The shared anatomical and physiologic substrate for both of these clinical problems is the neural innervation of the cranial circulation. Functional imaging with positron emission tomography has shed light on the genesis of both syndromes, documenting activation in the midbrain and pons in migraine and in the hypothalamic gray in cluster headache. These areas are involved in the pain process in a permissive or triggering manner rather than as a response to first-division nociceptive pain impulses. In a positron emission tomography study in cluster headache, however, activation in the region of the major basal arteries was observed. This is likely to result from vasodilation of these vessels during the acute pain attack as opposed to the rest state in cluster headache, and represents the first convincing activation of neural vasodilator mechanisms in humans. The observation of vasodilation was also made in an experimental trigeminal pain study, which concluded that the observed dilation of these vessels in trigeminal pain is not inherent to a specific headache syndrome, but rather is a feature of the trigeminal neural innervation of the cranial circulation. Clinical and animal data suggest that the observed vasodilation is, in part, an effect of a trigeminoparasympathetic reflex. The data presented here review these developments in the physiology of the trigeminovascular system, which demand renewed consideration of the neural influences at work in many primary headaches and, thus, further consideration of the physiology of the neural innervation of the cranial circulation. We take the view that the known physiologic and pathophysiologic mechanisms of the systems involved dictate that these disorders should be collectively regarded as neurovascular headaches to emphasize the interaction between nerves and vessels, which is the underlying characteristic of these syndromes. Moreover, the syndromes can be understood only by a detailed study of the cerebrovascular physiologic mechanisms that underpin their expression.
J Cereb Blood Flow Metab 1999 Feb
PMID:The trigeminovascular system in humans: pathophysiologic implications for primary headache syndromes of the neural influences on the cerebral circulation. 1002 65

Cytidine-5'-diphosphate choline (CDP-choline; citicoline) is an essential endogenous compound normally produced by the organism and is a source of cytidine and choline. Our recent studies on acute pain models demonstrate that intracerebroventricularly administered CDP-choline produces antinociception via supraspinal alpha-7 nicotinic acetylcholine receptors-mediated mechanism in rats. However, it remains to be elucidated which other supraspinal mechanisms are involved in the antinociceptive effect of CDP-choline. In this study, we investigated the role of the supraspinal opioidergic, GABAergic, alpha-adrenergic and serotonergic receptors in CDP-choline-induced antinociception. The antinociceptive effect of CDP-choline was evoked by the intracerebroventricular (i.c.v.) administration. Two different pain models were utilized: thermal paw withdrawal test and mechanical paw pressure test. The i.c.v. administration of CDP-choline (0.5, 1.0 and 2.0 micromol) produced dose-dependent antinociception. Non-specific opioid receptor antagonist naloxone (10 microg; i.c.v.) and GABA(B) receptor antagonist CGP-35348 (20 microg; i.c.v.) pretreatments inhibited the antinociceptive effects of CDP-choline (1.0 micromol; i.c.v.). In contrast, the alpha-1 adrenergic receptor antagonist prazosin (20 microg; i.c.v.), alpha-2 adrenergic receptor antagonist yohimbine (30 microg; i.c.v.) and non-specific serotonin receptor antagonist methysergide (20 microg; i.c.v.) pretreatments had no effect on CDP-choline-induced antinociception in the thermal paw withdrawal test and in the mechanical paw pressure test. Therefore, it can be postulated that i.c.v. administered CDP-choline exerts antinociceptive effect mediated by supraspinal opioid and GABA(B) receptors in acute pain models. Furthermore, supraspinal alpha-adrenergic and serotonergic receptors do not appear to be involved in the antinociceptive effect of CDP-choline.
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PMID:Possible involvement of supraspinal opioid and GABA receptors in CDP-choline-induced antinociception in acute pain models in rats. 1753 79

The evidence that action shapes perception has become widely accepted, for example, in the domain of vision. However, the manner in which action-relevant factors might influence the neural dynamics of acute pain processing has remained underexplored, particularly the functional roles of anterior insula (AI) and midanterior cingulate cortex (mid-ACC), which are frequently implicated in acute pain. To address this, we examined a unique group of heterozygous carriers of the rare R221W mutation on the nerve growth factor (NGF) gene. R221W carriers show a congenitally reduced density of C-nociceptor afferent nerves in the periphery, but can nonetheless distinguish between painful and nonpainful stimulations. Despite this, carriers display a tendency to underreact to acute pain behaviorally, thus exposing a potential functional gap in the pain-action relationship and allowing closer investigation of how the brain integrates pain and action information. Heterozygous R221W carriers and matched controls performed a functional magnetic resonance imaging (fMRI) task designed to dissociate stimulus type (painful or innocuous) from current behavioral relevance (relevant or irrelevant), by instructing participants to either press or refrain from pressing a button during thermal stimulation. Carriers' subjective pain thresholds did not differ from controls', but the carrier group showed decreased task accuracy. Hemodynamic activation in AI covaried with task performance, revealing a functional role in pain-action integration with increased responses for task-relevant painful stimulation ("signal," requiring button-press execution) over task-irrelevant stimulation ("noise," requiring button-press suppression). As predicted, mid-ACC activation was associated with action execution regardless of pain. Functional connectivity between AI and mid-ACC increased as a function of reported urge to withdraw from the stimulus, suggesting a joint role for these regions in motivated action during pain. The carrier group showed greater activation of primary sensorimotor cortices-but not the AI and mid-ACC regions-during pain and action, suggesting compensatory processing. These findings indicate a critical role for the AI-mid-ACC axis in supporting a flexible, adaptive action selection during pain, alongside the accompanying subjective experience of an urge to escape the pain.
Cereb Cortex 2020 Jul 30
PMID:Mutation Carriers with Reduced C-Afferent Density Reveal Cortical Dynamics of Pain-Action Relationship during Acute Pain. 3236 82