A SIMPLE LABORATORY MODEL FOR INDUCING AND MEASURING PAIN IN SMALL EXPERIMENTAL ANIMALS Original Article MONU YADAV, MILIND PARLE* Pharmacology Division, Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar 125001 (Haryana) India Email: mparle@rediffmail.com Received: 28 Feb 2016 Revised and Accepted: 17 May 2016 ABSTRACT Objective: Pain, an unpleasant sensation that we all experience in daily life, is an alert mechanism to prevent impending tissue injury. The animal models employed for screening of analgesic agents include pain-state models based on the use of thermal, mechanical electrical and chemical stimuli. This study was undertaken with an objective to design, develop and fabricate a new animal model for screening analgesics. Methods: In the present study, a humble attempt is made to develop a new animal model for screening analgesics overcoming the limitations of earlier models. The utility of the newly developed laboratory model (M-model) of pain was compared with already established models. Results: A simple laboratory model for screening of analgesics was developed in the present study. In this study, endurance time was defined as the time for which, the animals were able to endure the cold surface of ice-floor. The animals assumed a flinching posture and fled to M-Zone when they were unable to withstand the cold surface. Endurance time was significantly and consistently enhanced by different classes of analgesic agents such as pentazocine, butorphanol, tramadol, diclofenac, ketoprofen and meloxicam. The findings obtained using M-model was in line with those obtained using already established models. Conclusion: An effective animal model for screening analgesics overcoming the limitations of earlier models was developed in this study. This model showed excellent face and predictive validity. Keywords: Pain, Analgesics, Cold stimuli, M-model, Flinching posture, Endurance time © 2016 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) INTRODUCTION Pain is a complex, unpleasant phenomenon composed of sensory and emotional experience that include time, intensity, emotion, cognition and motivation originating from damaged tissue [1]. It plays an important role as an alarm/signal that helps to protect the living organisms and provokes avoidance behaviour, which arrests the potentially damaging consequences and facilitates fundamental biological functions such as inflammation or healing [2]. One-third of the world’s population suffers from persistent or recurrent pain. Nociceptors are the particular sensory receptors responsible for the detection of noxious stimuli, transforming the stimuli into electrical signals, which are then conducted to the CNS [3]. There are the free nerve endings of primary afferent Aδ and C fibres distributed throughout the body they can be stimulated by thermal, mechanical, electrical and chemical stimuli. Inflammatory mediators (eg. bradykinin, serotonin, prostaglandins, and cytokines) are released from damaged tissue and can stimulate nociceptors. They can also act by reducing the activation threshold of nociceptors so that the stimulation required to cause activation is less. In addition to the Aδ and C fibres that carry noxious sensory information, there are primary afferent Aβ fibres that bring non-noxious stimuli. These fibres possess different characteristics that allow the transmission of particular types of sensory information. Aβ fibres are highly myelinated and of large diameter, therefore allowing fast signal conduction. They have a low activation threshold and generally respond to light touch and transmit nonnoxious stimuli [4]. They respond to mechanical and thermal stimuli. C fibres are unmyelinated and are also the smallest type of primary afferent fibre. Hence, they allow the slowest conduction. C fibres respond to chemical, thermal and mechanical stimuli. Cold stimuli are that tactile sensibility and motor function deteriorate while pain perception persists. Nociception are the neural processes of encoding and processing noxious stimuli. Pain in response to a non- nociceptive stimulus is known as allodynia and increased pain sensitivity is hyperalgesia. Chronic pain is associated with conditions such as back injury, migraine headaches, arthritis, diabetic neuropathy, and cancer. Many of the currently available pain therapies cause uncomfortable to deleterious side effects because of lack of perfect animal models for screening of different types of analgesics. Animal models serve as indispensable tools for discovering new medicines as well as for the analysis of the magnitude of causes, biomarkers, and pathophysiological changes, which bring about symptoms analogous to those of patients with a specific disorder. Since human life is precious, it becomes necessary to test new medicines in small animals before applying to human beings. Animal models provide an opportunity to decipher the relationships between the nervous system and animal behaviours as they serve as obligatory tools for screening of new drugs [5]. Pain cannot be monitored directly in animals, but can only be measured by examining their responses to nociceptive stimuli [6]. Noxious stimulus is often used in animal models to damage a specific tissue partially in order to produce pain or inflammation. The observed reactions are almost always motor responses ranging from spinal reflexes to complex behaviour. Animal models serve as indispensable tools for discovering medicines useful in the treatment of human diseases. Tail-flick technique and hot-plate test are commonly used for screening analgesic agents, although both of these models use heat as the noxious stimulus. At present, there are several tests in literature, which employ cold stimulus for studying nociception in animal’s viz. Paw or tail withdrawal after immersion in cold water [7, 8] or water- alcohol bath [9], ethyl chloride spray [10], direct application of cold acetone [11] or contact with a Peltier the mode [12]. However, most of these methods impose limitations on the testing conditions [13]. New laboratory models are difficult to develop particularly in the area of neuropharmacology, because of the complexity of the human neuronal network. Since the brain of animals is not so well developed as compared to human brain, it becomes a tough task to produce neurological disorders in laboratory animals. An ideal laboratory model for screening International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 8, Issue 7, 2016