EXPERIMENTAL MODELS AND TESTS FOR NOCICEPTIVE AND NEUROPATHIC PAIN EVALUATION
Keywords:
neuropathic pain, nociceptive pain, animal models, experimental tests, rodentsAbstract
Pain, both acute and chronic, is an extremely prevalent symptom and remains a significant health problem with a great impact on function and quality of life. There are many experimental tests and models for pain evaluation, which are used during the preclinical characterization of drugs. Rodents are widely used to study the pathophysiology of pain as studies in humans are difficult to perform and ethically limited. The use of animal models can reveal the mechanisms, side-effects, and new effective therapeutic possibilities for patients suffering from acute and chronic pain syndromes, which could alter our clinical outlook. The wide range of animal models allows exploration of pain mediators and mechanisms, different pain etiologies and manifestations, and could reveal the mode of action of analgesics. In this review, the most commonly used animal models and experimental tests used in the study of nociceptive and neuropathic pain are discussed. For nociceptive pain examination, stimulus-evoked methods and temperature preference tests are used. The tests with a mechanical stimulus include the Paw pressure test, Pin-prick test, Incapacitance Test, and Von Frey Test. Tests with a chemical stimulus, such as the Formalin test and Abdominal writhing test are described. The tests with a heat stimulus include the Hot Plate Test, Plantar Test, and Tail‐Flick Test. Acetone Spray Test like a test with a cold stimulus is also summarized. To study neuropathic pain, the ideal methods should induce solely sensory neurons dysfunction, such as allodynia and hyperalgesia for short periods. Models of diabetic polyneuropathy, chemotherapy-induced painful peripheral neuropathy (CIPN), chronic constriction injury of n. ischiadicus, and spinal nerve ligation in rats are described. CIPN is most often induced by vinca alkaloids (vinblastine, vincristine), platinum derivatives (cisplatin, oxaliplatin, carboplatin), and taxanes (docetaxel, paclitaxel). Depending on the chemotherapeutic agent used, CIPN can be pure sensory neuropathy or mixed sensorimotor neuropathy with or without autonomic nervous system dysfunction. The occurrence and severity of the neurotoxicity depend on the type of drug used and are dose-dependent. The rate of CIPN correlates to the cumulative dose delivered and dose per treatment cycle. For neuropathic pain examination, tests with a mechanical stimulus (Von Frey Hair Test), a heat stimulus (Heath Plantar Test), and a cold stimulus (Cold plate test) are used. The methodology of each animal model is specific and results can be greatly influenced even by slight changes related to the study design. Different experimental models for pain evaluation were developed over the years and the search for new methods will continue in the future.
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