Evidence-based clinical practice guideline for the pharmacologic management of acute dental pain in adolescents, adults, and older adults: A report from the American Dental Association Science and Research Institute, the University of Pittsburgh, and the University of Pennsylvania.

Background: A panel convened by the American Dental Association Science and Research Institute, the University of Pittsburgh, and the University of Pennsylvania conducted systematic reviews and meta-analyses and formulated evidence-based recommendations for the pharmacologic management of acute dental pain after simple and surgical tooth extraction(s) and for the temporary management (ie, definitive dental treatment not immediately available) of toothache associated with pulp and periapical diseases in adolescents, adults, and older adults.

Types Of Studies Reviewed: The panel conducted 4 systematic reviews to determine the effect of opioid and nonopioid analgesics, local anesthetics, corticosteroids, and topical anesthetics on acute dental pain. The panel used the Grading of Recommendations, Assessment, Development and Evaluation approach to assess the certainty of the evidence and the Grading of Recommendations, Assessment, Development and Evaluation Evidence-to-Decision Framework to formulate recommendations.

Evidence-based clinical practice guideline for the pharmacologic management of acute dental pain in children: A report from the American Dental Association Science and Research Institute, the University of Pittsburgh School of Dental Medicine, and the Center for Integrative Global Oral Health at the University of Pennsylvania.

Background: A guideline panel convened by the American Dental Association Council on Scientific Affairs, American Dental Association Science and Research Institute, University of Pittsburgh School of Dental Medicine, and Center for Integrative Global Oral Health at the University of Pennsylvania conducted a systematic review and meta-analyses and formulated evidence-based recommendations for the pharmacologic management of acute dental pain after 1 or more simple and surgical tooth extractions and the temporary management of toothache (that is, when definitive dental treatment not immediately available) associated with pulp and furcation or periapical diseases in children (< 12 years).

Types Of Studies Reviewed: The authors conducted a systematic review to determine the effect of analgesics and corticosteroids in managing acute dental pain. They used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty of the evidence and the Grading of Recommendations Assessment, Development and Evaluation Evidence to Decision framework to formulate recommendations.

Proposed Guideline Revisions for Dental Sedation and General Anesthesia: Why Target the Safest Level of Sedation?

Recently proposed revisions to the American Dental Association's Guidelines for the Use of Sedation and General Anesthesia by Dentists, aimed at improving safety in dental offices, differentiate between levels of sedation based on drug-induced changes in physiologic and behavioral states. However, the author of this op-ed is concerned the proposed revisions may have far-reaching and unintended consequences.

Prescribing Opioid Analgesics for Acute Dental Pain: Time to Change Clinical Practices in Response to Evidence and Misperceptions.

As the nation comes to terms with a prescription opioid epidemic, dentistry is beginning to understand its own unintentional contribution and seek ways to address it. The article urges dental providers to reexamine entrenched prescribing habits and thought patterns regarding treatment of acute dental pain. It points to evidence suggesting that nonsteroidal anti-inflammatory drugs are nonaddictive and usually more effective for managing many cases of acute dental pain.

Changing Paradigms for Acute Dental Pain: Prevention Is Better Than PRN.

A B S T R A C T The drugs available for the management of acute orofacial pain have changed very little since the introduction of ibuprofen into practice 40 years ago. Orally effective opioids, acetaminophen, aspirin and NSAIDs remain the mainstay of analgesic therapy. Increased recognition of the societal and personal impact of opioid diversion and abuse requires re-examination of the traditional approach of prescribing an opioid-containing analgesic combination to be administered by the patient "as needed" (PRN) starting postoperatively.

Research design considerations for single-dose analgesic clinical trials in acute pain: IMMPACT recommendations.

This article summarizes the results of a meeting convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) on key considerations and best practices governing the design of acute pain clinical trials. We discuss the role of early phase clinical trials, including pharmacokinetic-pharmacodynamic (PK-PD) trials, and the value of including both placebo and active standards of comparison in acute pain trials. This article focuses on single-dose and short-duration trials with emphasis on the perioperative and study design factors that influence assay sensitivity.

Prescription of opioid analgesics for nontraumatic dental conditions in emergency departments.

Background: Opioid analgesics prescribed for nontraumatic dental conditions (NTDCs) by emergency physicians continue to receive attention because of the associated potential for misuse, abuse and addiction. This study examined rates of prescription of opioid analgesics and types of opioid analgesics prescribed for NTDC visits in U.S.

Nitric oxide is negatively correlated to pain during acute inflammation.

Background: The role that nitric oxide (NO) plays in modulating pain in the periphery is unclear. We show here, the results of two independent clinical studies (microdialysis and gene expression studies) and a pilot dose finding study (glyceryl trinitrate study), to study the role of NO in the early phase of acute inflammatory pain following oral surgery. The effect of ketorolac on NO production and nitric oxide synthase (NOS) gene expression was also studied.

Long-acting local anesthetics and perioperative pain management.

Although the use of long-acting local anesthetics has become a useful therapeutic approach for managing peri- and postoperative pain, recent evidence reveals unexpected outcomes. This article reviews the clinical use of long-acting local anesthetics, presents current clinical research findings, and makes recommendations for their use.

Kinin B1 receptors contributes to acute pain following minor surgery in humans.

Background: Kinins play an important role in regulation of pain and hyperalgesia after tissue injury and inflammation by activating two types of G-protein-coupled receptors, the kinin B1 and B2 receptors. It is generally accepted that the B2 receptor is constitutively expressed, whereas the B1 receptor is induced in response to inflammation. However, little is known about the regulatory effects of kinin receptors on the onset of acute inflammation and inflammatory pain in humans.

Mechanisms of non-opioid analgesics beyond cyclooxygenase enzyme inhibition.

Non-opioid analgesics including both selective and non-selective cyclooxygenase (COX) inhibitors and acetaminophen are the most widely used treatments for pain. Inhibition of COX is thought to be largely responsible for both the therapeutic and adverse effects of this class of drugs. Accumulating evidence over the past two decades has demonstrated effects of non-opioids beyond the inhibition of COX and prostaglandin synthesis that might also explain their therapeutic and adverse effects.

Genetic contributions to clinical pain and analgesia: avoiding pitfalls in genetic research.

Unlabelled: Understanding the genetic basis of human variations in pain is critical to elucidating the molecular basis of pain sensitivity, variable responses to analgesic drugs, and, ultimately, to individualized treatment of pain and improved public health. With the help of recently accumulated knowledge and advanced technologies, pain researchers hope to gain insight into genetic mechanisms of pain and eventually apply this knowledge to pain treatment.

Perspective: We critically reviewed the published literature to examine the strength of evidence supporting genetic influences on clinical and human experimental pain.

Genome-wide screen identifies drug-induced regulation of the gene giant axonal neuropathy (Gan) in a mouse model of antiretroviral-induced painful peripheral neuropathy.

Painful peripheral neuropathy is a debilitating complication of the treatment of HIV with nucleoside reverse transcriptase inhibitors (NRTIs). Patients are living longer with these drugs; however many develop excruciating, unremitting, and often treatment-limiting neuropathy that is resistant to conventional pain management therapies. Improving patient comfort and quality of life is paramount and depends on a clearer understanding of this devastating side effect.

Upregulation of IL-6, IL-8 and CCL2 gene expression after acute inflammation: Correlation to clinical pain.

Tissue injury initiates a cascade of inflammatory mediators and hyperalgesic substances including prostaglandins, cytokines and chemokines. Using microarray and qRT-PCR gene expression analyses, the present study evaluated changes in gene expression of a cascade of cytokines following acute inflammation and the correlation between the changes in the gene expression level and pain intensity in the oral surgery model of tissue injury and acute pain. Tissue injury resulted in a significant upregulation in the gene expression of interleukin-6 (IL-6; 63.

Genome-wide association study of acute post-surgical pain in humans.

Aims: Testing a relatively small genomic region with a few hundred SNPs provides limited information. Genome-wide association studies (GWAS) provide an opportunity to overcome the limitation of candidate gene association studies. Here, we report the results of a GWAS for the responses to an NSAID analgesic.

Individualized pain medicine.

Since the first draft of the human genome was published 10 years ago, scientists have tried to develop new treatment strategies for various types of diseases based on individual genomes. It is called personalized (or individualized) medicine and is expected to increase efficacy and reduce adverse reactions of drugs. Much progress has been made with newly developed technologies, though individualized pain medicine is still far from realization.

The differential effects of bupivacaine and lidocaine on prostaglandin E2 release, cyclooxygenase gene expression and pain in a clinical pain model.

Background: In addition to blocking nociceptive input from surgical sites, long-acting local anesthetics might directly modulate inflammation. In the present study, we describe the proinflammatory effects of bupivacaine on local prostaglandin E2 (PGE2) production and cyclooxygenase (COX) gene expression that increases postoperative pain in human subjects.

Methods: Subjects (n = 114) undergoing extraction of impacted third molars received either 2% lidocaine or 0.

Stimulating the development of mechanism-based, individualized pain therapies.

Biomedical science has greatly improved our understanding of pain in recent decades, but few novel molecular entities that address fundamentally new pain mechanisms have entered the clinic, despite dramatically increased pharmaceutical investment. Indeed, virtually all new analgesics approved over the past 25 years are derivatives or reformulations of opioids or aspirin-like drugs, existing drugs given for a new indication or older drugs given by a different route of administration. Here, we discuss factors contributing to this lack of innovation in therapies for pain and advocate public-private partnerships (PPPs) to translate new knowledge into more efficacious and safer treatments.

Lack of influence of GTP cyclohydrolase gene (GCH1) variations on pain sensitivity in humans.

Objectives: To assess the effect of variations in GTP cyclohydrolase gene (GCH1) on pain sensitivity in humans.

Methods: Thermal and cold pain sensitivity were evaluated in a cohort of 735 healthy volunteers. Among this cohort, the clinical pain responses of 221 subjects after the surgical removal of impacted third molars were evaluated.