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The Pronociceptive Activity of Spinal Dynorphin A is not due to Sensitization of Wide Dynamic Range Neurons
Author(s) -
Cai Alice,
Bannister Kirsty,
Rankin David,
Dickenson Anthony,
Lai Josephine
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.799.3
Subject(s) - dynorphin , dynorphin a , nociception , sensitization , opioid , spinal cord , medicine , endocrinology , opioid peptide , calcitonin gene related peptide , receptor , nociceptor , chemistry , neuroscience , neuropeptide , biology , immunology
Intrathecal administration of dynorphin A to the lumbar spinal cord induces transient hypersensitivity in naïve rats; this effect is blocked by dynorphin A antiserum, suggesting the existence of an underlying non‐opioid, pronociceptive mechanism of dynorphin A. Here we examined whether dynorphin A may promote the sensitization of wide dynamic range (WDR) neurons. In vivo extracellular recordings were performed on the lumbar spinal cord of anesthetized rats in the presence of a dose range of dynorphin A(1–13) (high affinity for opioid receptors) or dynorphin A(2–13) (Ki > 10 uM for opioid receptors). WDR neurons’ response was attenuated in naïve rats by dynorphin A(1–13). This attenuation was of greater magnitude in spinal nerve ligated rats with lower intensity thermal and mechanical responses. Dynorphin A(2–13) did not potentiate WDR response to nociceptive inputs in naive rats. These findings suggest that dynorphin A activates opioid receptors at the WDR to attenuate nociceptive transduction under physiological conditions. Thus, WDR neuron sensitization is unlikely to be a mechanism of the pronociceptive actions of intrathecal dynorphin A. This study is supported in part by NIH grant T37 MD001427.