Human Experimental Pain Models for Assessing the Therapeutic Efficacy of Analgesic Drugs

Olesen, Anne Estrup; Andresen, Trine; Staahl, Camilla; Drewes, Asbjørn Mohr

doi:10.1124/pr.111.005447

Cited by 205 publications

(230 citation statements)

References 495 publications

(783 reference statements)

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“…This is not possible for paracetamol as its mechanism of action is not known. In two recent reviews, Staahl et al [31] and Olesen et al [32] concluded that analgesia from paracetamol is difficult to detect in experimental acute pain models. Paracetamol-induced analgesia should be assessed with very sensitive methods like evoked brain potentials or EEG rather than subjective pain ratings [33].…”

Section: Discussionmentioning

confidence: 99%

The Effect of Paracetamol and Tropisetron on Pain: Experimental Studies and a Review of Published Data

Tiippana

Hamunen

Kontinen

et al. 2012

Basic Clin Pharma Tox

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Experimental studies suggest that paracetamol-induced analgesia is mediated via central serotonergic pathways and attenuated by 5-HT3-antagonists. However, clinical studies do not support this, and 5-HT3-antagonists are expected to reduce pain by blocking the descending pronociceptive pathway. The current project tested whether tropisetron attenuates analgesia by paracetamol. Two randomized, double-blind, crossover studies with 18 healthy male volunteers in each were performed. Pain stimuli were cold water immersion (cold pressor test), contact heat pain (study 1) and electrical stimulation (study 2). In both studies, tropisetron 5 mg i.v. or saline was administered, followed by paracetamol 2 g i.v. 30 min. later. Individual changes in heat and cold pain intensity, cold pain tolerance and unpleasantness were recorded. The same thresholds were also expressed as scores (% of the individual score at baseline). Additionally, previously published findings on the effects of paracetamol and its interaction with 5HT3-antagonists in human experimental pain models were reviewed. After calculation of the sensory and pain scores (%), tropisetron seemed to amplify the analgesic action of paracetamol. Paracetamol 2 g i.v. did not show any statistically significant analgesia in thermal tests (study 1), or differences in sensory, pain detection or moderate pain thresholds of the electrical stimulus (study 2). As paracetamol did not have a measurable analgesic effect in these tests, no conclusions can be drawn about the interaction between paracetamol and tropisetron. However, tropisetron may have an analgesic effect of its own. Clinicians should not avoid using these drugs together, unless larger clinical studies indicate otherwise.

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Section: Discussionmentioning

confidence: 99%

The Effect of Paracetamol and Tropisetron on Pain: Experimental Studies and a Review of Published Data

Tiippana

Hamunen

Kontinen

et al. 2012

Basic Clin Pharma Tox

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“…By characterizing analgesics in both healthy subjects and patients, a translational connection between early phase development and the clinic can be established. It may also be used to provide information on the pain physiology and pathophysiology in these populations 14 . Eventually, the ability to link the efficacy profile of a drug to the pain profile of a patient could help guide individualized treatments in the future 1 .…”

Section: Discussionmentioning

confidence: 99%

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

Hay

Okkerse

Amerongen

et al. 2016

JoVE

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Human pain models are useful in the assessing the analgesic effect of drugs, providing information about a drug's pharmacology and identify potentially suitable therapeutic populations. The need to use a comprehensive battery of pain models is highlighted by studies whereby only a single pain model, thought to relate to the clinical situation, demonstrates lack of efficacy. No single experimental model can mimic the complex nature of clinical pain. The integrated, multi-modal pain task battery presented here encompasses the electrical stimulation task, pressure stimulation task, cold pressor task, the UVB inflammatory model which includes a thermal task and a paradigm for inhibitory conditioned pain modulation. These human pain models have been tested for predicative validity and reliability both in their own right and in combination, and can be used repeatedly, quickly, in short succession, with minimum burden for the subject and with a modest quantity of equipment. This allows a drug to be fully characterized and profiled for analgesic effect which is especially useful for drugs with a novel or untested mechanism of action.

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“…We used blunt pressure algometry to ascertain whether post-exercise pain was driven by peripheral input from deep seated strictures such as muscle and connective tissue [4]. Sensitivity to blunt pressure was pronounced immediately after inger trigger exercises 1cm above the medial epicondyle and 1 cm under the medial epicondyle but not at other locations.…”

Section: Discussionmentioning

confidence: 99%

“…Symptoms are delayed in onset with severity reaching a peak between 24 to 72 hours and disappearing by seven days after exercise. Experimentally-induced DOMS is frequently used in experimental settings as an injurious model of muscle pain [4,5]. Commonly, large muscle groups such as the hamstrings are used because protocols to induce DOMS are readily available.…”

Section: Introductionmentioning

confidence: 99%

Characterisation of Delayed Onset of Muscle Soreness (DOMS) in the hand, wrist and forearm using a finger dynamometer: A pilot study

Jones¹

2017

J Sports Med Ther

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Background: Experimentally-induced delayed-onset muscle soreness of large muscle groups is frequently used in as an injurious model of muscle pain. We wanted to develop an experimental model of DOMS to to mimic overuse injuries from sports where repeated fi nger fl exion activity is vital such as rock climbing. The aim of this pilot study was to evaluate the utility of a 'fi nger trigger device' to induce DOMS in the fi ngers, hands, wrists and lower arms.Methods: A convenient sample of six participants completed an experiment in which they undertook fi nger exercises to exhaustion after which measurements of pain, skin sensitivity to fi ne touch, forearm circumference and grip strength in the hand, wrist and forearm were taken from the experimental and contralateral nonexercised (control) arms. Results:Pain intensity was greater in the experimental arm at rest and on movement when compared with the control arm up to 24 hours after exercise, although the location of pain varied between participants. Pressure pain threshold was signifi cantly lower in the experimental arm compared with the control arm immediately after exercises locations close to the medial epicondyle but not at other locations. There were no statistical signifi cant differences between affected and non-affected limbs for mechanical detection threshold, forearm circumference or grip strength. Conclusion:Repetitive fi nger fl exion exercises of the index fi nger by pulling a trigger against a resistance can induced DOMS. We are currently undertaking a more detailed characterization of sensory and motor changes following repetitive fi nger fl exion activity using a larger sample.

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Human Experimental Pain Models for Assessing the Therapeutic Efficacy of Analgesic Drugs

Cited by 205 publications

References 495 publications

The Effect of Paracetamol and Tropisetron on Pain: Experimental Studies and a Review of Published Data

The Effect of Paracetamol and Tropisetron on Pain: Experimental Studies and a Review of Published Data

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

Characterisation of Delayed Onset of Muscle Soreness (DOMS) in the hand, wrist and forearm using a finger dynamometer: A pilot study

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