s25ab_12

Future directions in pain management

D.E. Furst¹, D.C. Manning²

¹Virginia Mason Research Center, Seattle, Washington, USA; ²Novartis Pharmaceutical Corporation, Clinical Research and Development, East Hanover, New Jersey, USA

ABSTRACT
Relevant aspects of pain physiology and anatomy are reviewed, including hyperalgesia (an exaggerated response to normally mild stimuli) and allodynia (pain in response to normally non-noxious stimuli). Although the principal animal models do an excellent job at separating thermal, mechanoreceptor, and visceral aspects of pain, they are not very good predictive models because human pain is more complex. Human pain includes overlapping aspects of specific pain types, such as spontaneous and induced pain, and is modified by gender, stress, states of vigilance, and depression.
Nonsteroidal anti-inflammatory drugs (NSAIDs) have both peripheral and central analgesic effects. While prostaglandin-mediated effects are clearly operative, there are also other potential mechanisms involved in many cases and these may be quite important in certain patients. Effects mediated by cyclooxygenase-1, leukotriene B4, and intracellular transcription elements such as peroxisomal proliferator-activated receptors gamma (PPARgamma) may account for part of the spectrum of NSAID actions.
Future directions for analgesic research are many, but include the use of nitric oxide (NO) NSAIDs; the possibility of decreasing NO in the central nervous system; inhibiting the vanilloid receptor-1; inhibiting adenosine kinase; activating PPARgamma; and mimicking superoxide dismutase, as well as combinations of complementary-acting analgesics.

Key words
Analgesia, mechanisms of NSAIDs.

Please address correspondence and reprint requests to: Professor Daniel Furst, MD, Virginia Mason Research Center, 1201 Ninth Avenue, Seattle, WA 98101, USA.
E-mail: CRGDEF@vmmc.org