BackgroundAδ and C fibers are the major pain-conducting nerve fibers, activate only partly the same brain areas, and are differently involved in pain syndromes. Whether a stimulus excites predominantly Aδ or C fibers is a commonly asked question in basic pain research but a quick test was lacking so far.Methodology/Principal FindingsOf 77 verbal descriptors of pain sensations, “pricking”, “dull” and “pressing” distinguished best (95% cases correctly) between Aδ fiber mediated (punctate pressure produced by means of von Frey hairs) and C fiber mediated (blunt pressure) pain, applied to healthy volunteers in experiment 1. The sensation was assigned to Aδ fibers when “pricking” but neither “dull” nor “pressing” were chosen, and to C fibers when the sum of the selections of “dull” or “pressing” was greater than that of the selection of “pricking”. In experiment 2, with an independent cohort, the three-descriptor questionnaire achieved sensitivity and specificity above 0.95 for distinguishing fiber preferential non-mechanical induced pain (laser heat, exciting Aδ fibers, and 5-Hz electric stimulation, exciting C fibers).ConclusionA three-item verbal rating test using the words “pricking”, “dull”, and “pressing” may provide sufficient information to characterize a pain sensation evoked by a physical stimulus as transmitted via Aδ or via C fibers. It meets the criteria of a screening test by being easy to administer, taking little time, being comfortable in handling, and inexpensive while providing high specificity for relevant information.
Ventilatory depression is a significant risk associated with the use of opioids. We assessed whether opioid-induced ventilatory depression can be selectively antagonized by an ampakine without reduction of analgesia. In 16 healthy men, after a single oral dose of 1,500 mg of the ampakine CX717, a target concentration of 100 ng/ml alfentanil decreased the respiratory frequency by only 2.9 +/- 33.4% as compared with 25.6 +/- 27.9% during placebo coadministration (P < 0.01).Blood oxygenation and the ventilatory response to hypercapnic challenge also showed significantly smaller decreases with CX717 than with placebo. In contrast, CX717 did not affect alfentanil-induced analgesia in either electrical or heat-based experimental models of pain. Both ventilatory depression and analgesia were reversed with 1.6 mg of naloxone. These results support the use of ampakines as selective antidotes in humans to counter opioid-induced ventilatory depression without affecting opioid-mediated analgesia.
We have conducted a meta-analysis of the clinical effects of morphine and hydromorphone to compare their benefit in analgesia. Embase and Medline were searched with an end-date of June 2009 for randomized, controlled trials or observational studies that addressed comparative analgesic and side-effects or particular side-effects. Two researchers independently identified included studies and extracted the data. Estimates of opioid effects were combined by using a random-effects model. Meta-analysis of eight studies suggested that hydromorphone (494 patients) provides slightly better (P=0.012) clinical analgesia than morphine (510 patients). The effect-size was small (Cohen's d=0.266) and disappeared when one study was removed, although the advantage of hydromorphone was more evident in studies of better quality (Jadad's rating). Side-effects were similar, for example, nausea (P=0.383, nine studies, 456 patients receiving hydromorphone and 460 morphine); vomiting (P=0.306, six studies, 246 patients receiving hydromorphone and 239 morphine); or itching (P=0.249, eight studies, 405 patients receiving hydromorphone, 410 morphine). This suggests some advantage of hydromorphone over morphine for analgesia. Additional potential clinical pharmacological advantages with regard to side-effects, such as safety in renal failure or during acute analgesia titration, are based on limited evidence and require substantiation by further studies.
Cannabinoids receive increasing interest as analgesic treatments. However, the clinical use of Δ 9 -tetrahydrocannabinol (Δ 9 -THC) has progressed with justified caution, which also owes to the incomplete mechanistic understanding of its analgesic effects, in particular its interference with the processing of sensory or affective components of pain. The present placebo-controlled crossover study therefore focused on the effects of 20 mg oral THC on the connectivity between brain areas of the pain matrix following experimental stimulation of trigeminal nocisensors in 15 non-addicted healthy volunteers. A general linear model (GLM) analysis identified reduced activations in the hippocampus and the anterior insula following THC administration. However, assessment of psychophysiological interaction (PPI) revealed that the effects of THC first consisted in a weakening of the interaction between the thalamus and the secondary somatosensory cortex (S2). From there, dynamic causal modeling (DCM) was employed to infer that THC attenuated the connections to the hippocampus and to the anterior insula, suggesting that the reduced activations in these regions are secondary to a reduction of the connectivity from somatosensory regions by THC. These findings may have consequences for the way THC effects are currently interpreted: as cannabinoids are increasingly considered in pain treatment, present results provide relevant information about how THC interferes with the affective component of pain. Specifically, the present experiment suggests that THC does not selectively affect limbic regions, but rather interferes with sensory processing which in turn reduces sensory-limbic connectivity, leading to deactivation of affective regions.
Increasing evidence about the central nervous representation of pain in the brain suggests that the operculo-insular cortex is a crucial part of the pain matrix. The pain-specificity of a brain region may be tested by administering nociceptive stimuli while controlling for unspecific activations by administering non-nociceptive stimuli. We applied this paradigm to nasal chemosensation, delivering trigeminal or olfactory stimuli, to verify the pain-specificity of the operculo-insular cortex. In detail, brain activations due to intranasal stimulation induced by non-nociceptive olfactory stimuli of hydrogen sulfide (5 ppm) or vanillin (0.8 ppm) were used to mask brain activations due to somatosensory, clearly nociceptive trigeminal stimulations with gaseous carbon dioxide (75% v/v). Functional magnetic resonance (fMRI) images were recorded from 12 healthy volunteers in a 3T head scanner during stimulus administration using an event-related design. We found that significantly more activations following nociceptive than non-nociceptive stimuli were localized bilaterally in two restricted clusters in the brain containing the primary and secondary somatosensory areas and the insular cortices consistent with the operculo-insular cortex. However, these activations completely disappeared when eliminating activations associated with the administration of olfactory stimuli, which were small but measurable. While the present experiments verify that the operculo-insular cortex plays a role in the processing of nociceptive input, they also show that it is not a pain-exclusive brain region and allow, in the experimental context, for the interpretation that the operculo-insular cortex splay a major role in the detection of and responding to salient events, whether or not these events are nociceptive or painful.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.