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The aim of this study is to evaluate the antihyperalgesic and antinociceptive effects of two formulations containing peat water extracts using a model of carrageenan-induced hyperalgesia, combined with a test with a mechanical stimulus, and a hot plate test. Rats were divided into seven groups (n = 6) and received local treatment with two peat formulations and two diclofenac formulations dissolved in carbopol gel and Wolff® basis creme, respectively. Carbopol gel, Wolff® basis creme and 0.9 % NaCl without tested substances were used as controls. Both peat formulations exerted an unambiguous antihyperalgesic effect 60 minutes after the treatment. In the hot plate test, the rats treated with the Wolff® basis creme peat formulation showed a tendency to prolonged latency on the first hour. The results could be explained by partial activation of peripheral α2-adrenoceptors and the possible COX-2 suppressive activity.

The safety of pharmacological, chemical agents, and dietary supplements gains a high level of public interest. The creation and introduction of new drugs go through two stages – preclinical and clinical. Pharmaceutical products must undergo a range of general toxicology studies during the preclinical stage to provide information on the safety of a potential new drug in at least two different animal species. General toxicology studies begin with an acute toxicity study of the compound and progress to longer exposure durations, a minimum of six months. The preclinical toxicity studies can be divided into 1) according to the duration of the survey and its purposes: acute, sub-acute, sub-chronic, and chronic toxicity studies; 2) according to the number of doses administered: single-dose toxicity studies (acute toxicity study) and repeated-dose toxicity studies (sub-acute, sub-chronic, and chronic toxicity studies); 3) according to the location of drug exposure: systemic toxicity studies (acute, sub-acute, sub-chronic, and chronic toxicity studies) and local toxicity studies (dermal toxicity, ophthalmic toxicity studies). This review will discuss the main methods for determining the sub-acute, sub-chronic, and chronic toxicity of chemical compounds. Sub-acute toxicity studies aim to determine the doses to be tested for sub-chronic toxicity. Long-term treatment with the substance under investigation allows the registration of a toxic effect, manifested after a certain latent period. Sub-chronic and chronic toxicity are investigated during the fourth phase of preclinical trials. During the trial, changes in body weight and water and food consumption, changes affecting the skin, fur, mucous membranes, respiratory and cardiovascular systems, behavior and motor activity, and blood and urine tests are monitored daily. Specific toxicological studies are conducted – a study of allergenicity, local tolerance, and toxicity, a study of immunotoxicity, a study of reproductive toxicity and teratogenicity, peri- and postnatal toxicity, mutagenicity, carcinogenicity, etc. After completion of the experiment and euthanasia of the animals, histological examinations are performed to establish potential adverse drug reactions. In this review, the most used tests in the study of the abovementioned different types of chronic toxicity are discussed. The safety of potential new drugs must be adequately assessed in preclinical studies with various methods for determining acute, sub-acute, sub-chronic, and chronic toxicity. If the test compound has shown acceptable efficacy and safety during preclinical testing, it moves on to testing in human clinical trials. [ABSTRACT FROM AUTHOR]

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, stimulusevoked 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. [ABSTRACT FROM AUTHOR]

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