Pain and u-shaped dose responses: occurrence, mechanisms, and clinical implications.
This article assesses pain within the context of the dose response. A substantial number of studies indicate that the dose response for pain-related endpoints is commonly biphasic, being independent of the type of biological model employed, endpoint measured, or agent tested. The quantitative features of the dose response are also remarkably consistent regardless of the receptor pathway that mediates the nociceptive response, indicating a likely downstream message convergence. These findings have important implications for drug discovery, development, and clinical evaluation.
Calabrese
Edward J
EJ
Department of Public Health, School of Public Health and Health Sciences, Environmental Health Sciences Division, University of Massachusetts, Amherst, Massachusetts 01003, USA. edwardc@schoolph.umass.edu
D000222:Adaptation, Physiological / Q000187:drug effects*; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051379:Mice; D009480:Neuropharmacology / Q000379:methods*; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement; D051381:Rats
D000700:Analgesics