Bunionectomy as an Acute Postoperative Pain Model: Overview of Common Experimental Methods, and Insights from Past Clinical Trials.

To obtain broad regulatory approval for a new analgesic agent in acute postoperative pain, US and European regulatory authorities require pivotal studies in both hard (bony) tissue pain and soft tissue pain. Bunionectomy is by far the most common hard tissue pivotal trial model, in spite of the fact that the model has limited relevance to clinicians prescribing pain drugs (pain from bunionectomy is not extreme or long-lasting, and is adequately treated by existing drugs). The authors outline the experimental characteristics that make bunionectomy an appealing study model for researchers despite its lack of clinical relevance compared to larger surgeries.

Preliminary validation of the Diversion Risk Scale (DRS): Using environmental and individual factors to predict opioid-related diversion events.

The standard of care calls for the assessment of patients with chronic pain prior to the initiation of opioids, with one part of this assessment including assessment of the risk of misuse of medications. However, traditional opioid risk assessment tools focus almost entirely on individual factors and on the risk of misuse and addiction to opioids. Diversion of opioid medications has been found to be not uncommon, but to date, there have been no assessment tools specifically designed to assess the risk of diversion.

Injectable Capsaicin for the Management of Pain Due to Osteoarthritis.

Capsaicin is a potent agonist of the TRPV1 channel, a transduction channel that is highly expressed in nociceptive fibers (pain fibers) throughout the peripheral nervous system. Given the importance of TRPV1 as one of several transduction channels in nociceptive fibers, much research has been focused on the potential therapeutic benefits of using TRPV1 antagonists for the management of pain. However, an antagonist has two limitations.

Number Of Clinical Trial Study Sites Impacts Observed Treatment Effect Size: An Analysis Of Randomized Controlled Trials Of Opioids For Chronic Pain.

Background: Many aspects of study conduct impact the observed effect size of treatment. Data were utilized from a recently published meta-analysis of randomized, double-blind, placebo-controlled, clinical trials performed for the United States Food and Drug Administration (FDA) approval of full mu-agonist opioids for the treatment of chronic pain.

Methods: The number of study sites in each clinical trial and standardized effect size (SES) were extracted and computed.

Analgesic efficacy, safety, and tolerability of a long-acting abuse-deterrent formulation of oxycodone for moderate-to-severe chronic low back pain in subjects successfully switched from immediate-release oxycodone.

Objectives: This post hoc analysis of data from a randomized, double-blind, placebo-controlled, enriched-enrollment randomized-withdrawal Phase III study evaluated the safety, tolerability, and analgesic efficacy of Oxycodone DETERx extended-release (ER), abuse-deterrent capsules (Xtampza ER) in subjects with chronic low back pain who were successfully transitioned from immediate-release (IR) oxycodone.

Methods: Continuous outcomes were analyzed using a mixed-model repeated-measures approach; binomial outcomes were analyzed using chi-squared; and time-to-event outcomes using Kaplan-Meier analyses.

Results: A total of 110 subjects previously prescribed IR oxycodone entered the Open-label Titration Phase.

Efficacy of opioids versus placebo in chronic pain: a systematic review and meta-analysis of enriched enrollment randomized withdrawal trials.

Introduction: Opioids have been used for millennia for the treatment of pain. However, the long-term efficacy of opioids to treat chronic non-cancer pain continues to be debated. To evaluate opioids' efficacy in chronic non-cancer pain, we performed a meta-analysis of published clinical trials for μ-opioid receptor agonists performed for US Food and Drug Administration approval.

Exploring the Interplay between Rescue Drugs, Data Imputation, and Study Outcomes: Conceptual Review and Qualitative Analysis of an Acute Pain Data Set.

In placebo-controlled acute surgical pain studies, provisions must be made for study subjects to receive adequate analgesic therapy. As such, most protocols allow study subjects to receive a pre-specified regimen of open-label analgesic drugs (rescue drugs) as needed. The selection of an appropriate rescue regimen is a critical experimental design choice.

Opioid and noradrenergic contributions of tapentadol in experimental neuropathic pain.

Tapentadol is a dual action molecule with mu opioid agonist and norepinephrine (NE) reuptake blocking activity that has recently been introduced for the treatment of moderate to severe pain. The effects of intraperitoneal (i.p.

Protein kinase C activation modulates reversible increase in cortical blood-brain barrier permeability and tight junction protein expression during hypoxia and posthypoxic reoxygenation.

Hypoxia (Hx) is a component of many disease states including stroke. Ischemic stroke occurs when there is a restriction of cerebral blood flow and oxygen to part of the brain. During the ischemic, and subsequent reperfusion phase of stroke, blood-brain barrier (BBB) integrity is lost with tight junction (TJ) protein disruption.