Spinal mechanisms of NPY analgesia

Peter A. Smith, Timothy D. Moran, Fuad Abdulla, Kiranjeet K. Tumber, Bradley K Taylor

Research output: Contribution to journalReview article

56 Citations (Scopus)

Abstract

We review previously published data, and present some new data, indicating that spinal application of neuropeptide Y (NPY) reduces behavioral and neurophysiological signs of acute and chronic pain. In models of acute pain, early behavioral studies showed that spinal (intrathecal) administration of NPY and Y2 receptor agonists decrease thermal nociception. Subsequent neurophysiological studies indicated that Y2-mediated inhibition of excitatory neurotransmitter release from primary afferent terminals in the substantia gelatinosa may contribute to the antinociceptive actions of NPY. As with acute pain, NPY reduced behavioral signs of inflammatory pain such as mechanical allodynia and thermal hyperalgesia; however, receptor antagonist studies indicate an important contribution of spinal Y1 rather than Y2 receptors. Interestingly, Y1 agonists suppress inhibitory synaptic events in dorsal horn neurons (indeed, well known μ-opioid analgesic drugs produce similar cellular actions). To resolve the behavioral and neurophysiological data, we propose that NPY/Y1 inhibits the spinal release of inhibitory neurotransmitters (GABA and glycine) onto inhibitory neurons, e.g. disinhibition of pain inhibition, resulting in hyporeflexia. The above mechanisms of Y1- and Y2-mediated analgesia may also operate in the setting of peripheral nerve injury, and new data indicate that NPY dose-dependently inhibits behavioral signs of neuropathic pain. Indeed, neurophysiological studies indicate that Y2-mediated inhibition of Ca2+ channel currents in dorsal root ganglion neurons is actually increased after axotomy. We conclude that spinal delivery of Y1 agonists may be of use in the treatment of chronic inflammatory pain, and that the use of Y1 and Y2 agonists in neuropathic pain warrants further consideration.

Original languageEnglish (US)
Pages (from-to)464-474
Number of pages11
JournalPeptides
Volume28
Issue number2
DOIs
StatePublished - Feb 1 2007

Fingerprint

Neuropeptide Y
Analgesia
Hyperalgesia
Acute Pain
Neurons
Neuralgia
Chronic Pain
Neurotransmitter Agents
Substantia Gelatinosa
Neuropeptide Y Receptors
Posterior Horn Cells
Axotomy
Pain
Peripheral Nerve Injuries
Abnormal Reflexes
Nociception
Spinal Ganglia
Glycine
gamma-Aminobutyric Acid
Opioid Analgesics

Keywords

  • Dorsal horn
  • Inflammatory pain
  • Neuropathic pain
  • Substantia gelatinosa
  • Synaptic transmission

Cite this

Smith, P. A., Moran, T. D., Abdulla, F., Tumber, K. K., & Taylor, B. K. (2007). Spinal mechanisms of NPY analgesia. Peptides, 28(2), 464-474. https://doi.org/10.1016/j.peptides.2006.09.029

Spinal mechanisms of NPY analgesia. / Smith, Peter A.; Moran, Timothy D.; Abdulla, Fuad; Tumber, Kiranjeet K.; Taylor, Bradley K.

In: Peptides, Vol. 28, No. 2, 01.02.2007, p. 464-474.

Research output: Contribution to journalReview article

Smith, PA, Moran, TD, Abdulla, F, Tumber, KK & Taylor, BK 2007, 'Spinal mechanisms of NPY analgesia', Peptides, vol. 28, no. 2, pp. 464-474. https://doi.org/10.1016/j.peptides.2006.09.029
Smith PA, Moran TD, Abdulla F, Tumber KK, Taylor BK. Spinal mechanisms of NPY analgesia. Peptides. 2007 Feb 1;28(2):464-474. https://doi.org/10.1016/j.peptides.2006.09.029
Smith, Peter A. ; Moran, Timothy D. ; Abdulla, Fuad ; Tumber, Kiranjeet K. ; Taylor, Bradley K. / Spinal mechanisms of NPY analgesia. In: Peptides. 2007 ; Vol. 28, No. 2. pp. 464-474.
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