title: Fixed-dose combinations for emerging treatment of pain.
abstract: BACKGROUND
  Pain is a large and growing medical need that is not currently being fully met, primarily due to the shortcomings of existing analgesics (insufficient efficacy or limiting side-effects). Better outcomes might be achieved using a combination of analgesics. The ratio of the combinations matters and should therefore be evaluated using rigorous quantitative and well-documented analysis.
  
  
  METHODS
  Advances have been made in understanding the normal physiology of pain processing, including the pathways and neurotransmitters involved. Insight has also been gained about physiological processes that can lead to different 'types' of pain and the transition from acute to chronic pain conditions. This 'multimechanistic' nature of most pains is better matched using a 'multimechanistic' rather than 'monomechanistic' analgesic approach. Such an approach - and the experimental design and data analysis to assess optimal combinations - is described and discussed.
  
  
  CONCLUSIONS
  There are sound pharmacologic, as well as practical, reasons for using combinations of drugs to treat pain. Compared with single agents, they offer a potential better match to the underlying pain physiology and thus greater efficacy or reduced side effects. The optimal efficacy and side-effect ratio must be determined in a scientifically rigorous manner.
authors.affiliation: Temple University School of Pharmacy, Department of Pharmaceutical Sciences, 3307 N. Broad Street, PA 19140, USA. robert.raffa@temple.edu
authors.forename: Robert B
authors.initials: RB
authors.lastname: Raffa
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Tallarida
authors.forename: Robert
authors.initials: R
authors.lastname: Taylor
authors.forename: Joseph V
authors.initials: JV
authors.lastname: Pergolizzi
mesh_terms: D000700:Analgesics / Q000008:administration & dosage* / Q000009:adverse effects; D000818:Animals; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D006801:Humans; D010146:Pain / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D059408:Pain Management / Q000379:methods*; D018570:Risk Assessment; D016896:Treatment Outcome
chemical_list: D000700:Analgesics; D004338:Drug Combinations