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

Abstract

AIMExperimental 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. METHODSA literature search was completed for randomized controlled studies that included human experimental pain models, healthy volunteers and non-opioid analgesics. RESULTSNonsteroidal 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.

Determining Pain Detection and Tolerance Thresholds Using an Integrated, Multi-Modal Pain Task Battery

“…While the aforementioned pain models provide a suitable basis for screening potentially analgesic drugs, other factors need to be considered, especially taking into account the pharmacological mechanisms of the drug and its pharmacokinetics 21 . Standard practice for researching analgesics should be applied, including the use of positive controls and designing studies that are randomized (balanced, where applicable), placebo-controlled, and double-blind.…”

Assessing analgesic actions of opioids by experimental pain models in healthy volunteers – an updated review

“…Assessment of the analgesic effects of opioids has most frequently been done by skin stimulation [6,32,45,49,54,86,97,105]. Fast acting opioids like alfentanil and remifentanil have been tested extensively and these pure m-receptor agonists have a short half-life and straightforward kinetics.…”

“…The next review will describe non-opioid analgesics tested in human pain models [6]. To be able to illustrate the importance of various experimental designs, only drugs that have been tested in at least five different trials each including at least seven volunteers were included.…”

Validation of the Simplified UVB Model to Assess the Pharmacodynamics of Analgesics in Healthy Human Volunteers

“…[14,15] Models inducing hyperalgesia can mimic clinical pain which is often associated with signs of hyperalgesia. The sunburn model uses UVB irradiation to induce stable primary and secondary hyperalgesia.…”