Analgesic sensitivity of two post-partum pain models

Post-partum uterine cramping and episiotomy pain are established, frequently used, clinical pain models for efficacy trials of investigational new analgesic agents. To determine the respective assay sensitivity of these two models in assessing relative efficacy, we reviewed data from 6 phase II, randomized, stratified, parallel, placebo-controlled, double-blind, single-dose studies involving hospitalized women with moderate or severe post-partum uterine cramping (332 patients) or episiotomy pain (434 patients). Using subjective reports as indices of response, patients rated pain intensity and relief at periodic interviews for 6-7 h. Post-partum uterine cramping showed excellent assay sensitivity for detecting differences among peripherally acting analgesics. In the same clinical trial this model could discriminate between a new drug and aspirin 650 mg, a standard reference analgesic, and between 2 graded doses of the new active agent (i.e., good upside sensitivity). In addition the uterine cramp model showed separation between placebo and all active agents (i.e., good downside sensitivity). Episiotomy pain demonstrated similar upside and downside discrimination in clinical trials of several weak centrally acting drugs. These data suggest that post-partum cramping is an excellent pain model for analgesic investigation of new non-steroidal anti-inflammatory drugs, and episiotomy pain for new weak narcotic and opioid analgesics.