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75–79 Prostaglandins are lipid-derived eicosanoids that are synthesized from arachidonic acid by COX isoenzymes COX-1 and COX-2. Prostaglandins have been shown to be involved in the sensitization and/or direct excitation of nociceptors by binding to several prostanoid receptors expressed by nociceptors (Fig. 65 Acute or chronic administration of a selective COX-2 inhibitor significantly attenuated both ongoing and movement-evoked pain. Whereas acute administration of a COX-2 inhibitor presumably reduces prostaglandins capable of activating sensory or spinal cord neurons, chronic inhibition of COX-2 also appears to simultaneously reduce osteoclastogenesis, bone resorption, and tumor burden.

However, it should be stressed that following cancerinduced injury to sensory neurons, areas of the spinal cord and central nervous system involved in the processing of somatosensory information also undergo a variety of neurochemical and cellular changes, known as central sensitization, that facilitate the transmission and conscious appreciation of both noxious and non-noxious sensory information. Thus, during the development of cancer, there is probably a slow but progressive neurochemical and cellular remodeling of both the peripheral and central nervous systems that inhibits, facilitates, or otherwise alters the transmission of somatosensory information from the damaged peripheral sensory fibers to the cerebral cortex, resulting in an altered and unwanted perception of both noxious and non-noxious sensory information.

In: Dickenson A, Besson J, eds. The pharmacology of pain. Handbook of experimental pharmacology. Berlin: Springer, 1997, pp 305–33. 53. Arner S, Meyerson BA. Lack of analgesic effect of opioids on neuropathic and idiopathic forms of pain. Pain 33:11–23, 1988. 54. Portenoy RK, Foley KM, Inturrisi CE. The nature of opioid responsiveness and its implications for neuropathic pain: new hypotheses derived from studies of opioid infusions. Pain 43:273–86, 1990. 55. Rowbotham MC, Reisner-Keller LA, Fields HL.

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18 Trading Champions Share Their Keys To Top Trading Profits by docchantw

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