The ability to detect and respond to aversive environmental stimuli is a basic feature of animals that is expressed in the term 'nociception.' Nociception and nociceptive responses provide an index of the sensitivity of individuals to aversive physical stimuli. Measurements of alterations in nociceptive responses (antinociception and analgesia) are commonly used to monitor the behavioral and physiological status of animals following experimental manipulation that usually, but not always, involve exposure to either noxious, stressful or potentially stressful physical and/or biological stimuli. This review briefly considers: i) the phylogenetic development of nociceptive responses and behaviors ii) evolutionary and comparative patterns of the neuromodulation of nociceptive behaviors by opioid peptides and other nonopioid peptidal regulatory mechanisms; iii) the effects of various biological variables, including; age, development, sex, and temporal factors (biological rhythms) on nociception in rodents.