Conclusions

The wealth of data that is now available on the properties of nociceptors indicates that these afferent fibers have unique properties beyond their fundamental one that distinguishes them from other sensory afferents as nociceptors, namely, the ability to respond only to stimuli that are potentially damaging to the organism. They express a unique blend of receptors and transmitter molecules, resulting in an ability to undergo sensitization peripherally and to induce central sensitization. They follow a different developmental timetable than nonnociceptive afferents, and they exhibit greater plasticity than nonnociceptive afferents. They activate unique populations of neurons in the central nervous system, and the inputs that they provide to the CNS are subject to modification by impulses in fibers descending from the medulla. These properties provide a significant targets for therapeutic intervention, a fortunate opportunity given the debilitating consequences of persistent pain. Although central targets certainly exist for a therapeutic approach, the nociceptor itself and neurons to which it projects would appear to be a particularly suitable focus for intervention because of their relative isolation as well as the chemical uniqueness referred to earlier.

Some important new approaches are already in progress. For example, it is known that the action of substance P released by nociceptive afferents is terminated by re-uptake into spinal neurons. This knowledge has been used to design a cytotoxin, substance P-saporin, whose uptake kills the cell. This treatment that kills certain populations of spinal neurons has been found to diminish inflammatory and neuropathic thermal hyperalgesia and mechanical allodynia with no loss of response to acute mild nociceptive stimuli. It is thus clear that continued exploration of the detailed molecular properties of nociceptors and their peripheral and central projections should be highly profitable from both the scientific and therapeutic points of view.

See Also the Following Articles

MIGRAINE • OPIATES • PAIN • PERIPHERAL NERVOUS SYSTEM

Suggested Reading

Baron, R., Levine, J. D., and Fields, H. L. (1999). Causalgia and reflex sympathetic dystrophy: Does the sympathetic nervous system contribute to the generation of pain? Muscle Nerve 22, 678-695.

Basbaum, A. I.,andWoolf,C. J. (1999). Pain. Curr. Biol. 9,R429-431.

Belmonte, C., and Cervero, F. (Eds.) (1996). The Neurobiology of Nociceptors. Oxford University Press, New York.

Dubner, R., and Gold, M. (Eds.) (1999). Colloquium on the Neurobiology of Pain. Proc. Natl. Acad. Sci. USA 96,7627-7755.

Fields, H. L., Rowbotham, M., and Baron, R. (1998). Postherpetic neuralgia: Irritable nociceptors and deafferentation. Neurobiol. Dis. 5, 209-227.

Julius, D., and Basbaum, A. I. (2001). Molecular mechanisms of nociception. Nature 413, 203-210.

Kumuzawa, T., Kruger, L., and Mizumura, K. (Eds.) (1996). The polymodal receptor—A gateway to pathological pain. Prog. Brain Res. 113.

Levine, J. D., Fields, H. L., and Basbaum, A. I. (1993). Peptides and the primary afferent nociceptor. J. Neurosci. 13, 2273-2286.

Lewin, G. R., and Mendell, L. M. (1993). Nerve growth factor and nociception. Trends Neurosci. 16, 353-359.

Melzack, R., and Wall, P. D. (ed.). (1999). Textbook of Pain. Churchill-Livingstone, New York.

Mendell, L. M., Albers, K. M., and Davis, B. M. (1999). Neuro-trophins, nociceptors, and pain. Microsc. Res. Tech. 45,252-261.

Scott, S. A. (Ed.) (1992). Sensory Neurons: Diversity, Development and Plasticity. Oxford University Press, New York.

Snider, W. D., and McMahon, S. B. (1998). Tackling pain at the source: New ideas about nociceptors. Neuron 20, 629-632.

Wood, J. N., and Perl, E. R. (1999). Pain. Curr. Opin. Genet. Dev. 9, 328-332.

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