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

Abstract

AIMExperimental pain models may help to evaluate the mechanisms of action of analgesics and target the clinical indications for their use. This review addresses how the efficacy of opioids can be assessed in human volunteers using experimental pain models. The drawback with the different study designs is also discussed. METHODA literature search was completed for randomized controlled studies which included human experimental pain models, healthy volunteers and opioids. RESULTSOpioids with a strong affinity for the m-opioid receptor decreased the sensation in a variety of experimental pain modalities, but strong tonic pain was attenuated more than short lasting pain and non-painful sensations. The effects of opioids with weaker affinity for the m-opioid receptor were detected by a more narrow range of pain models, and the assessment methods needed to be more sensitive. CONCLUSIONThe way the pain is induced, assessed and summarized is very important for the sensitivity of the pain models. This review gives an overview of how different opioids perform in experimental pain models. Generally experimental pain models need to be designed with careful consideration of pharmacological mechanisms and pharmacokinetics of analgesics. This knowledge can aid the decisions needed to be taken when designing experimental pain studies for compounds entering phase 1 clinical trials.

Thermal and Pressure Pain Sensitivity in Patients with Unilateral Shoulder Pain: Comparison of Involved and Uninvolved Sides

“…These pain assays measure different aspects of pain processing, with pressure stimuli involving sensitivity of deep tissue afferents and thermal stimuli involving C-fiber hyperexcitability (especially temporal summation). 5,50,51 This is not a new finding, as there is low to moderate correlation across different pain stimuli when examined on the same individual. 34,36 However, this is important to recognize, as many prior studies 15,17,18,[20][21][22]31 that have reported on side-to-side comparisons utilized only a single type of stimulus.…”

“…Such use of pressure stimuli is also supported by the association between local PPT and clinical pain intensity. Palpation is the clinical correlate of pressure algometry 50 and may be useful as a measure of pain response, especially to provoke pain in specific regions of muscles. 3,4,26 Furthermore, it may be possible to distinguish between altered peripheral and central pain processes with the application of pressure stimuli.…”

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

“…As the physiology of deep and superficial pain differs, the results will furthermore be divided into the tissue (skin, muscle or viscera) in where the pain was induced, and into modalities used for pain stimulation. For a more thorough introduction to human experimental pain models, see the first review in this series involving opioid analgesics [5].…”

Pain perception in Parkinson’s disease: A systematic review and meta-analysis of experimental studies

“…Future studies are needed to help establish whether pain hypersensitivity in PD extends to suprathreshold levels of pain, and insights may also be gained from the use of ischemic and dermal capsaicin experimental pain models that evoke several aspects of chronic pain whilst preserving strict experimental control [50]. More research involving preclinical models and neuroimaging techniques in humans would also help to elucidate potential mechanistic pathways underlying altered pain perception in PD.…”