Background & Aims
20-30% of population suffers from chronic pain (1). Unfortunately, pain treatments present analgesic effects associated to adverse effects. Pharmaceutical research needs new compounds without side effects. For this reason, we have developed an innovative package including pain and adverse effect evaluation using ALGOGramTM and Adversafe.
Methods
The ALGOGramTM is a battery of 11 validated animal models/tests spanning a broad range of pain areas. The concept is an assessment of efficacy based on a group size of n=4 rats/model/test, thus providing a general pharmacological profile while reducing costs; assays/test are run in parallel, thus minimizing timelines.
Adversafe is a package of 8 tests/parameters representative of major adverse effects observed with the currently used analgesics (group size of n=5 rats/test).
To validate the package, various reference drugs classically used in clinical pain practice (morphine, pregabalin, duloxetine, acetaminophen and diclofenac) were evaluated in the 11 pain models / tests (models: CCI, oxaliplatin, carrageenan, kaolin, post-operative and TNBS; tests: paw pressure, tail flick, writhing and formalin). Behavioral and acute toxicity were also evaluated (Adversafe). Results are expressed for each group as 2 dashboard illustrating analgesic efficacy and major adverse effects.
Results
Morphine (3 mg/kg, s.c.) was active in all 11 different pain models and presented a decrease of the intestinal transit and locomotor activity. In contrast, pregabalin was active in several hypersensitive pain models and induced sedation. Diclofenac and acetaminophen displayed antinociceptive properties in some inflammatory pain models. Duloxetine and diclofenac induced stomachal ulcers.
Conclusions
The package provides a rapid and predictive evaluation of investigational compounds in 11 different pain models/tests, enabling their prioritization for fully-powered studies and an overview of the adverse effects. Shortened timelines and reduced costs are possible due to small group sizes that are run largely in parallel. In summary, the ALGOGramTM and the Adversafe may prove to be useful in a signal detection exercise for a broad range of potential analgesic activity and safety of the compounds.
References
(1) Cohen et al., Lancet, 2021
Presenting Author
Violette Maffre
Poster Authors
Topics
- Models: Acute Pain