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Analgesic medications in dentistry are indicated for the relief of acute pain, postoperative pain, chronic pain as well as controlling adjunctive intraoperative pain. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) has shown an effective reduction of postendodontic pain by action on the cyclooxygenase pathway. Another medication which is used recently is corticosteroid which enables the reduction of pain. They are hormones secreted from the adrenal gland and have strong anti-inflammatory actions. This review aims to compare the analgesic efficacy of NSAIDs and corticosteroids when administered through oral route for reducing postendodontic pain. The secondary objective was to assess the anesthetic effect of the nerve block when an oral premedication of NSAIDs or corticosteroids was administered. The databases of PubMed, ScienceDirect, LILACS, and Cochrane were searched for related topics from 1983 to April 2020. Bibliographies of clinical studies were identified in the electronic search. Clinical studies with postendodontic pain reduction using NSAIDs and corticosteroids were selected. Clinical studies that met all inclusion criteria were reviewed. Data extraction was performed independently by two reviewers. All individuals who administered single dose analgesic (NSAID or corticosteroid) before initiating root canal treatment were taken into inclusion criteria. All the relevant data were extracted from the selected studies were reviewed by two independent reviewers using a standardized data collection form, and in case of disagreement, a third reviewer was enquired to achieve a consensus. Risk of bias of the selected studies was done using Cochrane Risk of Bias Tool (version 1). Mean pain score levels at various time intervals showed an increased analgesic success rate for corticosteroids ( 32-1) in comparison to NSAIDs ( 32-21.4). Anesthetic effect of the nerve block administered was seen to be better when an oral premedication of corticosteroids (38.2%-80.8%) was given in comparison to NSAID (25.5%-73.1%). From the present study, it can be concluded that oral administration of corticosteroids provides a better analgesic efficacy when compared to NSAIDs as an oral premedication for postoperative pain reduction. It can also be concluded that corticosteroids when used as an oral premedication provide a better anesthetic effect of the nerve block administered when compared to NSAIDs given as an oral premedication. These findings could help the clinician determine which pretreatment analgesic would have a better effect in reduction of pain posttreatment as well as increasing the anesthetic efficacy of administered block. Systematic Review Registration Number: CRD42021235394.
Learn More >Migraine is a leading cause of disability among the adult population and is a significant burden on the economies of the world. Studies into the underlying causes of migraine have spanned centuries but its underlying mechanisms are still not fully understood. In recent years, accumulating evidence implicates that microbiota-mediated gut-brain crosstalk may contribute to the pathogenesis of migraine. This review provides a brief account of the history of migraine theories and summarizes the recent studies showing how gut microbiota is involved in the pathophysiology of migraine. Future research perspectives for better understanding the role of the gut microbiota in migraine are also discussed.
Learn More >The incidence and severity of chronic postoperative pain (POP) are major clinical challenges, and presurgical conditioned pain modulation (CPM) and pain catastrophizing scale (PCS) assessments have exhibited predictive values for POP. However, whether CPM and PCS assessments are also predictive of acute POP is unknown.
Learn More >Chronic pain arising from peripheral nerve injuries represents a significant clinical challenge because even the most efficacious anticonvulsant drug treatments are limited by their side effects profile. We investigated pain behavior, changes in axonal signal conduction and excitability of trigeminal neurons, and expression of voltage-gated sodium channels (NaVs) in the infraorbital nerve and trigeminal ganglion (TG) after infraorbital nerve entrapment (IoNE). Compared to Sham, IoNE rats had increased A- and C-fiber compound action potentials (CAPs) and Aδ component of A-CAP area from fibers innervating the vibrissal pad. After IoNE, A- and C-fiber CAPs were more sensitive to blockade by tetrodotoxin (TTX), and those fibers that were TTX-resistant were more sensitive to blockade by the NaV1.8 selective blocker, A-803467. Although NaV1.7 blocker, ICA-121431 alone, did not affect Aδ-fiber signal propagation, cumulative application with A-803467 and 4,9-anhydro-TTX significantly reduced the Aδ-fiber CAP in IoNE rats. In patch clamp recordings from small- and medium-sized TG neurons, IoNE resulted in reduced action potential (AP) depolarizing current threshold, hyperpolarized AP voltage threshold, increased AP duration, and a more depolarized membrane potential. While the transcripts of most NaVs were reduced in the ipsilateral TG after IoNE, NaV1.3, NaV1.7, and NaV1.8 mRNAs, and NaV1.8 protein, were significantly increased in the nerve. Altogether, our data suggest that axonal redistribution of NaV1.8, and to a lesser extent NaV1.3, and NaV1.7 contributes to enhanced nociceptive signal propagation in peripheral nerve after IoNE.
Learn More >Chronic pain causes disability and is prevalent in the general population. Opioids are a part of a multimodal strategy for pain management. Methadone, a cheap and long-acting synthetic opioid, may represent an option for those who have limited access to the aforementioned class of analgesics. We aimed to provide a real-world evidence for the analgesic use of methadone, compared with morphine.
Learn More >Trauma and compression are common causes of peripheral neuropathic pain (NP) refractory to conventional medical management (CMM). The role of perineural interventions in relieving this type of pain is unclear.
Learn More >Ketamine, an anesthetic adjunct, is routinely administered as part of a balanced general anesthetic technique. We recently showed that the acute analgesic and dissociation properties of ketamine are separable to suggest that distinct neural circuits underlie these states.
Learn More >Beta 2 adrenergic receptor (β2 AR) activation in the central and peripheral nervous system has been implicated in nociceptive processing in acute and chronic pain settings with anti-inflammatory and anti-allodynic effects of β2-AR mimetics reported in several pain states. In the current study, we examined the therapeutic efficacy of the β2-AR agonist clenbuterol in a rat model of persistent postsurgical hypersensitivity induced by disruption of descending noradrenergic signaling in rats with plantar incision. We used growth curve modeling of ipsilateral mechanical paw withdrawal thresholds following incision to examine effects of treatment on postoperative trajectories. Depletion of spinal noradrenergic neurons delayed recovery of hypersensitivity following incision evident as a flattened slope compared to non-depleted rats (-1.8 g/day with 95% CI -2.4 to -1.085, p < 0.0001). Chronic administration of clenbuterol reduced mechanical hypersensitivity evident as a greater initial intercept in noradrenergic depleted (6.2 g with 95% CI 1.6 to 10.8, p = 0.013) and non-depleted rats (5.4 g with 95% CI 1.2 to 9.6, p = 0.018) with plantar incision compared to vehicle treated rats. Despite a persistent reduction in mechanical hypersensitivity, clenbuterol did not alter the slope of recovery when modeled over several days (p = 0.053) or five weeks in depleted rats (p = 0.64). Systemic clenbuterol suppressed the enhanced microglial activation in depleted rats and reduced the density of macrophage at the site of incision. Direct spinal infusion of clenbuterol failed to reduce mechanical hypersensitivity in depleted rats with incision suggesting that beneficial effects of β2-AR stimulation in this model are largely peripherally mediated. Lastly, we examined β2-AR distribution in the spinal cord and skin using hybridization and IHC. These data add to our understanding of the role of β2-ARs in the nervous system on hypersensitivity after surgical incision and extend previously observed anti-inflammatory actions of β2-AR agonists to models of surgical injury.
Learn More >Distinct types of dorsal root ganglion sensory neurons may have unique contributions to chronic pain. Identification of primate sensory neuron types is critical for understanding the cellular origin and heritability of chronic pain. However, molecular insights into the primate sensory neurons are missing. Here we classify non-human primate dorsal root ganglion sensory neurons based on their transcriptome and map human pain heritability to neuronal types. First, we identified cell correlates between two major datasets for mouse sensory neuron types. Machine learning exposes an overall cross-species conservation of somatosensory neurons between primate and mouse, although with differences at individual gene level, highlighting the importance of primate data for clinical translation. We map genomic loci associated with chronic pain in human onto primate sensory neuron types to identify the cellular origin of chronic pain. Genome-wide associations for chronic pain converge on two different neuronal types distributed between pain disorders that display different genetic susceptibilities, suggesting both unique and shared mechanisms between different pain conditions.
Learn More >Clinical outcome assessments (COAs) measure outcomes that are meaningful to patients in clinical trials and are critical for determining whether a treatment is effective. The objectives of this study are to (1) describe the different types of COAs and provide an overview of key considerations for evaluating COAs, (2) review COAs and other outcome measures for chronic pain treatments that are recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) or other expert groups, and (3) review advances in understanding pain-related COAs that are relevant to clinical trials. The authors reviewed relevant articles, chapters, and guidance documents from the European Medicines Agency and U.S. Food and Drug Administration. Since the original core set of outcome measures were recommended by IMMPACT 14 years ago, several new advancements and publications relevant to the measurement or interpretation of COAs for chronic pain trials have emerged, presenting new research opportunities. Despite progress in the quality of measurement of several outcome domains for clinical trials of chronic pain, there remain some measurement challenges that require further methodological investigation.
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