Pharmacokinetics |
Design experiment according to pharmacokinetic profile. |
If possible, select drugs with specific and potent analgesic effect especially if models only permit less intense pain intensity. |
Select appropriate (and preferable relative high) dose. |
Use dose-response regimens when possible. |
Stimulations |
Select models with optimal control of stimulus intensities. |
Use models with large dynamic range. |
Use models evoking peripheral and central pain mechanisms (e.g., single and repeated electrical stimulation) where appropriate. |
Consider multimodal tests that are advantageous in many experimental conditions. |
In selected cases use multitissue stimulations. |
Design protocol with stimulations at appropriate time according to pharmacokinetics. |
Select deep stimuli whenever possible to mimic the clinical situation. |
Use tonic rather than phasic stimulation to evaluate pain intensity. |
When feasible, add models evoking allodynia and hyperalgesia to mimic clinical pain. |
Use suprathreshold pain stimuli especially in evaluation of weak analgesics. |
Select the stimulus paradigms according to known drug mechanisms (e.g., summated stimuli in evaluation of NMDA antagonists). |
Consider selecting stimulus according to known pain mechanisms (e.g., projection of referred pain in functional diseases). |
Use models with activation predominantly of C fibers. |
Apply “methods of limits” if possible. |
Only models tested for reliability should be selected. |
Prefer models with high internal validity (i.e., most sensitive for analgesics in the painful range of sensations). |
Prefer models with high external validity (i.e., mimics clinical pain and drug mechanisms). |
Consider arousal status of the subjects (avoid prolonged experiments without breaks). |
Assessments |
Use both subjective and objective pain assessments if feasible. |
Select reliable psychophysical scales. |
In selected cases, use more qualitative pain assessments (e.g., McGill Pain Questionnaire). |
Select explanatory neurophysiologic or imaging methods if feasible. |
Use predefined and robust output parameters. |
In selected cases, use supplementary assessments (e.g., referred pain areas). |
Subjects |
In design, re-evaluate ethical considerations. |
Consider selection of subjects using psychological evaluation. |
Consider enriched enrollment (i.e., evaluate sensitivity to the tests or drugs). |
Select appropriate sample (volunteers/patient groups). |
Consider selection according to gender, age, genotype, etc. |
Reduce anxiety through screening, pretesting and proper instruction. |
Train subjects in pain ratings to increase reliability. |
Laboratory |
Use well educated and experienced staff trained in the tests. |
Use same person to perform tests for repeated assessments. |
Pay attention to theoretical and practical education of staff. |
Ensure recommendations for good clinical and laboratory practice are followed. |
Avoid any interruption and disturbing factors during experiments. |
Isolate equipment between experiments to ensure stability (mainly for advanced electronic equipment). |
Reconsider safety issues whenever necessary. |
Data analysis |
Evaluate according to predefined primary and secondary endpoints. |
Use statistical adjustment for multiple comparisons. |
Perform baseline corrections in repeated testing. |
Use expert evaluation of neurophysiological/imaging data. |