A Simple Contact Heat Experimental Pain Model for Evaluation of Analgesic Agents in Healthy Volunteers

Abstract 

Background

Human experimental pain models help to understand the mechanism of the underlying clinical pain conditions and can be adopted to test analgesic efficacy of drugs used in the management of pain. In early phases, the clinical development of new analgesic agents is severely hindered due to lack of reliable sensitive tests for the experimental pain models.

Objective

The aim of the present study was to standardize and validate a simple contact heat pain model that can be used for future screening of various analgesic agents.

Methods

The method was standardized by recording heat detection and heat pain detection threshold in degrees centigrade in 24 healthy volunteers. Reproducibility of the test procedure was evaluated by recording the thermal threshold parameters by a single observer on 2 sessions (inter-day reproducibility) and a second observer on 1 session (inter-observer reproducibility) separately. Validity of model was further tested by evaluating the analgesic effect of tramadol on 12 healthy volunteers.

Results

Thermal pain model using contact heat method was found to produce low variability with coefficient of variation <5%. Inter-observer and inter-day reproducibility was very good, as shown by Bland–Altman Plot; with most of the values within 2 SD. There was a significant difference in both heat detection threshold and heat pain detection threshold produced by tramadol, as compared with placebo (P < 0.05).

Conclusions

The newly developed pain model produces a type of experimental pain that is responsive to analgesic effects of tramadol at clinically relevant doses. The model might be useful in early screening of new therapeutic agents before proceeding to expensive clinical trials in acute and chronic pain sufferers.

Key Words:  contact heat , heat detection , heat pain detection , reproducibility , tramadol , validation