Pain
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Chronic neuropathic pain is often refractory to current pharmacotherapies. The rodent Mas-related G-protein-coupled receptor subtype C (MrgC) shares substantial homogeneity with its human homologue, MrgX1, and is located specifically in small-diameter dorsal root ganglion neurons. However, evidence regarding the role of MrgC in chronic pain conditions has been disparate and inconsistent. ⋯ Further, in a mouse model of trigeminal neuropathic pain, microinjection of JHU58 into ipsilateral subnucleus caudalis inhibited mechanical hypersensitivity in wild-type but not Mrg KO mice. Finally, JHU58 attenuated the miniature excitatory postsynaptic currents frequency both in medullary dorsal horn neurons of mice after trigeminal nerve injury and in lumbar spinal dorsal horn neurons of mice after SNL. We provide multiple lines of evidence that MrgC agonism at spinal but not peripheral sites may constitute a novel pain inhibitory mechanism that involves inhibition of peripheral excitatory inputs onto postsynaptic dorsal horn neurons in different rodent models of neuropathic pain.
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Review Comparative Study
A Comparison of the Clinical and Experimental Characteristics of Four Acute Surgical Pain Models: Dental Extraction, Bunionectomy, Joint Replacement and Soft Tissue Surgery.
When a clinical trial of an analgesic produces a negative finding, it is important to consider the influence (if any) of experimental error on the validity of that result. Although efforts to identify and minimize experimental error in chronic pain investigations have begun in earnest, less work has been performed on the optimization of acute pain methodology. Of the acute surgical pain methodology articles that have been published over the last decade, almost all focus on either the dental or bunion model. ⋯ The purposes of this review were (1) to qualitatively describe the clinical and experimental characteristics of the 4 classic surgical models: dental extraction, bunionectomy, joint replacement, and soft tissue surgery; and (2) to quantitatively compare the models by analyzing 3 factors: effect size, enrollment rate, and demographics. We found that the dental extraction and bunionectomy models had higher assay sensitivity than the joint replacement and soft tissue surgery models. It is probable that this finding is secondary to the superior experimental conditions under which the dental and bunion models are executed (utilization of few centers that have the ability to reduce surgical, anesthetic, and postoperative confounders).
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Randomized Controlled Trial
Repetitive Transcranial Magnetic Stimulation Induced Analgesia Depends on N-Methyl-D-Aspartate Glutamate Receptors.
We investigated the role of glutamate N-methyl-d-aspartate (NMDA) receptors in the analgesic effects induced by repetitive transcranial magnetic stimulation (rTMS). In a randomized, double-blind, crossover study, we compared the effects of ketamine and placebo on the analgesic effects of motor cortex (M1) or dorsolateral prefrontal cortex/premotor cortex (DLPFC/PMC) stimulation. Three groups of 12 healthy volunteers underwent active rTMS (10Hz, 80% resting motor threshold, 1,500 pulses per session) of the right M1, active stimulation of the right DLPFC/PMC, or sham stimulation during 2 experimental sessions 2 weeks apart. ⋯ Ketamine injection significantly decreased the analgesic effects of both M1 and DLPFC/PMC stimulation. The decrease in the analgesic effect of rTMS was not associated with changes in cortical excitability parameters, which were not influenced by rTMS following the administration of either saline or ketamine. Thus, rTMS-induced analgesia depends on glutamate NMDA receptors and may involve long-term potentiation-like mechanisms.
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Randomized Controlled Trial
Remembering the dynamic changes in pain intensity and unpleasantness: a psychophysical study.
This study investigated the short-term memory of dynamic changes in acute pain using psychophysical methods. Pain intensity or unpleasantness induced by painful contact-heat stimuli of 8, 9, or 10s was rated continuously during the stimulus or after a 14-s delay using an electronic visual analog scale in 10 healthy volunteers. Because the continuous visual analog scale time courses contained large amounts of redundant information, a principal component analysis was applied to characterize the main features inherent to both the concurrent rating and retrospective evaluations. ⋯ Analysis performed on the components confirmed significant memory distortions and revealed that the discriminative information about pain dimensions in concurrent ratings was partly or completely lost in retrospective ratings. Importantly, our results highlight individual differences affecting these memory processes. These results provide further evidence of the important transformations underlying the processing of pain in explicit memory and raise fundamental questions about the conversion of dynamic nociceptive signals into a mental representation of pain in perception and memory.
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Pain is a highly personal experience that varies substantially among individuals. In search of an anatomical correlate of pain sensitivity, we used voxel-based morphometry to investigate the relationship between grey matter density across the whole brain and interindividual differences in pain sensitivity in 116 healthy volunteers (62 women, 54 men). Structural magnetic resonance imaging (MRI) and psychophysical data from 10 previous functional MRI studies were used. ⋯ No regions showed a positive relationship to pain sensitivity. These structural variations occurred in areas associated with the default mode network, attentional direction and shifting, as well as somatosensory processing. These findings underscore the potential importance of processes related to default mode thought and attention in shaping individual differences in pain sensitivity and indicate that pain sensitivity can potentially be predicted on the basis of brain structure.