Assessing efficacy of non‐opioid analgesics in experimental pain models in healthy volunteers: an updated review

Abstract

Experimental pain models may help to evaluate the mechanisms of analgesics and target the clinical indications for their use. This review, the second in a series of two, addresses how the efficacy of non-opioid analgesics have been assessed in human volunteers using experimental pain models. A literature search was completed for randomized controlled studies that included human experimental pain models, healthy volunteers and non-opioid analgesics. Nonsteroidal anti-inflammatory drugs worked against various types of acute pain as well as in hyperalgesia. Analgesia from paracetamol was difficult to detect in experimental pain and the pain needed to be assessed with very sensitive methods like evoked brain potentials. The N-methyl-D-aspartate antagonists exemplified by ketamine generally needed strong, long-lasting or repeated pain in the skin for detectable analgesia, whereas pain in muscle and viscera generally was more easily attenuated. Gabapentin worked well in several models, particularly those inducing hyperalgesia, whereas lamotrigine was weak in modulation of experimental pain. Imipramine attenuated pain in most experimental models, whereas amitriptyline had weaker effects. Delta-9-tetrahydrocannabinol attenuated pain in only a few models. Pain induction and assessment are very important for the sensitivity of the pain models. Generally, experimental pain models need to be designed with careful consideration of the pharmacological mechanisms and pharmacokinetics of analgesics. The drawback with the different study designs is also discussed. This knowledge can aid the decisions that need to be taken when designing experimental pain studies for compounds entering Phase I and II trials.