The spinal biology in humans and animals of pain states generated by persistent small afferent input
10.1073/pnas.96.14.7680
Crossref journal-article
Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences (341)
Abstract

Behavioral models indicate that persistent small afferent input, as generated by tissue injury, results in a hyperalgesia at the site of injury and a tactile allodynia in areas adjacent to the injury site. Hyperalgesia reflects a sensitization of the peripheral terminal and a central facilitation evoked by the persistent small afferent input. The allodynia reflects a central sensitization. The spinal pharmacology of these pain states has been defined in the unanesthetized rat prepared with spinal catheters for injection and dialysis. After tissue injury, excitatory transmitters (e.g., glutamate and substance P) acting though N- methyl- d -aspartate (NMDA) and neurokinin 1 receptors initiate a cascade that evokes release of ( i ) NO, ( ii ) cyclooxygenase products, and ( iii ) activation of several kinases. Spinal dialysis show amino acid and prostanoid release after cutaneous injury. Spinal neurokinin 1, NMDA, and non-NMDA receptors enhance spinal prostaglandin E2 release. Spinal prostaglandins facilitate release of spinal amino acids and peptides. Activation by intrathecal injection of receptors on spinal C fiber terminals (μ,/∂ opiate, α2 adrenergic, neuropeptide Y) prevents release of primary afferent peptides and spinal amino acids and blocks acute and facilitated pain states. Conversely, consistent with their role in facilitated processing, NMDA, cyclooxygenase 2, and NO synthase inhibitors act to diminish only hyperalgesia. Importantly, spinal delivery of several of these agents diminishes human injury pain states. This efficacy emphasizes ( i ) the role of facilitated states in humans, ( ii ) shows the importance of spinal systems in human pain processing, and ( iii ) indicates that these preclinical mechanisms reflect processes that regulate the human pain experience.

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Yaksh, T. L., Hua, X.-Y., Kalcheva, I., Nozaki-Taguchi, N., & Marsala, M. (1999). The spinal biology in humans and animals of pain states generated by persistent small afferent input. Proceedings of the National Academy of Sciences, 96(14), 7680–7686.

Authors 5
  1. Tony L. Yaksh (first)
  2. Xiao-Ying Hua (additional)
  3. Iveta Kalcheva (additional)
  4. Natsuko Nozaki-Taguchi (additional)
  5. Martin Marsala (additional)
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Dates
Type When
Created 23 years, 1 month ago (July 26, 2002, 10:38 a.m.)
Deposited 3 years, 4 months ago (April 13, 2022, 3:43 p.m.)
Indexed 3 weeks, 5 days ago (Aug. 2, 2025, 1:01 a.m.)
Issued 26 years, 1 month ago (July 6, 1999)
Published 26 years, 1 month ago (July 6, 1999)
Published Online 26 years, 1 month ago (July 6, 1999)
Published Print 26 years, 1 month ago (July 6, 1999)
Funders 0

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@article{Yaksh_1999, title={The spinal biology in humans and animals of pain states generated by persistent small afferent input}, volume={96}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.96.14.7680}, DOI={10.1073/pnas.96.14.7680}, number={14}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Yaksh, Tony L. and Hua, Xiao-Ying and Kalcheva, Iveta and Nozaki-Taguchi, Natsuko and Marsala, Martin}, year={1999}, month=jul, pages={7680–7686} }