Black box experimental approaches for the investigation of pain mechanism. To investigate acute or physiological pain in animals, sensory noxious stimuli are typically used to induce behavioral motor responses in awake or lightly-anesthetized animals. For noxious stimuli, thermal or mechanical stimuli are commonly used. For motor responses, withdrawal reflexes or escaping responses are measured. In some cases, electrodes are used to measure muscle activities (e.g., visceral pain responses). The manipulation or pharmacological agents are introduced to the central nervous systems at different levels (i.e., spinal cord by intrathecal catheters; supraspinal areas by microinjections). Reduction or inhibition of behavioral motor responses is used as the endpoint of pain responses. Complete inhibition of motor responses such as tail-flick or hindpaw withdrawal due to the manipulation in the 'black box' is treated as 100% analgesic or antinociceptive. Similar experimental approaches are often used for studying chronic pain as well in various animal models.