Future directions in pain management

Relevant aspects of pain physiology and anatomy are reviewed, including hyp eralgesia (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; a nd visceral aspects of pain, they are not very good predictive models becau se human pain is more complex. Human pain includes overlapping aspects of s pecific pain types, such as spontaneous and induced pain, and is modified b y gender; stress, states Of vigilance, and depression. Nonsteroidal anti-inflammatory drugs (NSAIDs) have both peripheral and cent ral analgesic effects. While prostaglandin-mediated effects are clearly ope rative, there are also other potential mechanisms involved in many cases an d these may be quite important in certain patients. Effects mediated by cyc looxygenase-1, leukotriene B4, and intracellular transcription elements suc h as peroxisomal proliferator-activated receptors gamma (PPARgamma) may acc ount for part of the spectrum of NSAID actions. Future directions for analgesic research are many, but include the use of n itric oxide (NO) NSAIDs; the possibility of decreasing NO in the central ne rvous system; inhibiting the vanilloid receptor-1; inhibiting adenosine kin ase; activating PPARgamma; and mimicking superoxide dismutase, as well as c ombinations of complementary-acting analgesics.