Enhanced release of adenosine in rat hind paw following spinal nerve ligation: Involvement of capsaicin-sensitive sensory afferents

Xue Jun Liu, T. D. White, J. Sawynok

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Modulation of endogenous adenosine levels by inhibition of adenosine metabolism produces a peripheral antinociceptive effect in a neuropathic pain model. The present study used microdialysis to investigate the neuronal mechanisms modulating extracellular adenosine levels in the rat hind paw following tight ligation of the L5 and L6 spinal nerves. Subcutaneous injection of 50 μl saline into the nerve-injured paw induced a rapid and short-lasting increase in extracellular adenosine levels in the subcutaneous tissues of the rat hind paw ipsilateral to the nerve injury. Saline injection did not increase adenosine levels in sham-operated rats or non-treated rats. The adenosine kinase inhibitor 5 -amino-5 -deoxyadenosine and the adenosine deaminase inhibitor 2 -deoxycoformycin, at doses producing a peripheral antinociceptive effect, did not further enhance subcutaneous adenosine levels in the nerve-injured paw. Systemic pretreatment with capsaicin, a neurotoxin selective for small-diameter sensory afferents, markedly reduced the saline-evoked release of adenosine in rat hind paw following spinal nerve ligation. Systemic pretreatment with 6-hydroxydopamine, a neurotoxin selective for sympathetic afferent nerves, did not affect release. These results suggest that following nerve injury, peripheral capsaicin-sensitive primary sensory afferent nerve terminals are hypersensitive, and are able to release adenosine following a stimulus that does not normally evoke release in sham-operated or intact rats. Sympathetic postganglionic afferents do not appear to be involved in such release. The lack of effect on such release by the inhibitors of adenosine metabolism suggests an altered peripheral adenosine system following spinal nerve ligation.

Original languageEnglish
Pages (from-to)379-387
Number of pages9
JournalNeuroscience
Volume114
Issue number2
DOIs
Publication statusPublished - Oct 1 2002
Externally publishedYes

Bibliographical note

Funding Information:
The present study was supported by the Canadian Institute of Health Research. X.J.L. is a recipient of the Izaak Walton Killam Memorial Scholarship.

ASJC Scopus Subject Areas

  • General Neuroscience

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