Pain is an unpleasant sensory and emotional experience associated with actual and potential tissue damage. Various types of pain are seen in humans, for example, somatic pain arising from the skin, muscles, joints, ligaments and bones, visceral pain, referred pain, neuropathic pain, cancer pain, and so on. Pain and nociception are explained. Nociception is the mechanism whereby noxious peripheral stimuli are transmitted to the central nervous system. Drugs in clinical use as analgesics belong to two main groups—narcotic or morphine group and analgesic-antipyretic (nonsteroidal anti inflammatory drugs) group. Animal models are explained. Hot plate method has been widely used to evaluate opioids analgesics. Radiant heat method, tail warm water immersion method, and tooth pulp electrical stimulation method are explained. Formalin test is a chronic pain model and highly sensitive for opioid-like drugs. Writhing tests is explained. Randall Selitto test is described. Inflammation increases the sensitivity to pain and decreases pain threshold. Neuropathic pain model is discussed. Identification of several types of opioid receptors in the brain has allowed performing in vitro binding tests to study the action of central analgesics. Various new receptors are identified by using in vitro methods as therapeutic targets for the treatment of pain, especially neuropathic and cancer pain such as receptors for nociceptin, vasoactive intestinal peptide, cannabinoids and vanilloid receptors. Opioid drugs exert their analgesic effects mainly through µ opioid receptors. 3H dihydromorphine is highly selective for µ receptors. The compounds that inhibit binding of 3H dihydromorphine in a synaptic membrane preparation from rat brain can be identified by this assay. Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) play a role in the altered transmission of sensory information in neuropathic pain (arising from trauma or compression injury of peripheral nerves).