The Value of the Dental Impaction Pain Model in Drug Development

Abstract

The modern version of the Dental Impaction Pain Model (DIPM) was developed in the mid-1970s. Since that time, several hundred studies have been conducted by numerous investigators. Today it is arguably the most utilized of all the acute pain models. Its popularity is due to the success rate of the studies, fast subject entry, and cost effectiveness. The surgical procedure is extremely standardized, and the surgery requires either minimal or no use of CNS depressant anesthetics. The methodology is similar to that utilized in other acute pain models; however, the DIPM is much more versatile than most other models. The model can be easily adapted to perform multiple-dose studies, pharmacokinetics/pharmacodynamics (PK/PD) correlations, preemptive interventions, and sleep-pain studies. A few investigators have even developed microdialysis techniques, wherein they insert probes into extraction sockets to collect exudates for measuring biochemical mediators of pain or drug levels at the site of injury. In many instances, an accomplished site can complete a study of several hundred subjects in approximately 3 months. There are studies in the literature that have incorporated up to six treatment arms in one study and clearly separated the drugs from each other. The exquisite assay sensitivity is due to the homogeneity of the study population, the predictable level and appropriate intensity of the postsurgical pain, and the minimizing of variability by using only one or two study centers. The DIPM has been employed to evaluate NSAIDs (both nonselective and selective Cox inhibitors), opioids and combination analgesics, as well as some investigational drugs with unique mechanisms of action. The model is particularly useful for proof-of-concept studies that require dose-ranging and profiling the time-effect curve for efficacy including onset, peak effect, and duration of analgesic activity.

Evaluation of the Dose Range of Etoricoxib in an Acute Pain Setting Using the Postoperative Dental Pain Model

“…It is likely that there is a ceiling effect in the dental pain model that is dependent on the number of teeth removed and/or the level of trauma that limits the upside sensitivity of the model to detect greater analgesic benefit with higher doses of NSAIDs. 19 The analgesic efficacy of NSAIDs, such as etoricoxib, has traditionally been attributed to their inhibition of prostaglandin synthesis, specifically their action on the cyclooxygenase-2 enzyme, which catalyzes the process. This inhibition of prostaglandin synthesis diminishes inflammation and, in turn, pain.…”

A Phase 2 Study of Lower-dose, Indomethacin Submicron Particle Capsules Demonstrates Early Onset of Acute Pain Relief

“…21 TOTPAR-4 and TOTPAR-8 were calculated by multiplying the patient's pain relief score (5-point categorical scale) at each time point by the time elapsed since their last assessment and then summing these values over the given time interval. 21 TOTPAR-4 and TOTPAR-8 were calculated by multiplying the patient's pain relief score (5-point categorical scale) at each time point by the time elapsed since their last assessment and then summing these values over the given time interval.…”

Orofacial pain

“…The dental impaction pain model has been developed as a standard clinical method for evaluating many analgesic drugs (54–56). Other investigators have used this model of acute inflammatory pain to evaluate preemptive anesthesia (57, 58), activation of endogenous opioid analgesic systems (59–62), local release of inflammatory mediators as collected by implanted microdialysis probes (63–66), other physiologic mechanisms (67), or the association of genetic polymorphisms with post-operative pain (68–70).…”