[Abstract Title]. - Society for Neuroscience

Disclosures: P. Kumar, None; S. Sirohi, None; S.V. Dighe, None; B.C. Yoburn, None.
Poster
270. Pain: Opioids and Other Analgesics II
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 270.14/HH13
Topic: D.08.r. Opioids and other analgesics
Support: NIH/NINDS R01NS043095
Title: Opioid-induced tactile hypernociception is attenuated by the CXCR4 antagonist,
AMD3100
Authors: *N. M. WILSON 1 , H. JUNG 2 , M. S. RIPSCH 3 , R. J. MILLER 2 , F. A. WHITE 3,4 ;
1 Pharmacol, Loyola Univ. Med. Ctr., Maywood, IL; 2 Molec Pharmacol and Biolog Chem,
Northwestern Univ., Chicago, IL; 3 Cell Biology, Neurobiology, and Anat., 4 Anesthesiol., Loyola
Univ. Chicago, Chicago, IL
Abstract: Morphine and related compounds are the first line of therapy in the treatment of
moderate to severe pain. Over time, individuals taking opioids can develop an increasing
sensitivity to noxious stimuli, even evolving into a painful response to previously non-noxious
stimuli (opioid-induced hyperalgesia; OIH). The mechanism underlying OIH is not well
understood although complex intracellular neural mechanisms, including opioid receptor
desensitization and down-regulation, are believed to be major mechanisms underlying OIH.
However, OIH may also be associated with changes in gene expression. A growing body of
evidence suggests that cellular exposure to mu agonists upregulate chemokines/receptors and
recent work from our lab implicates chemokine upregulation in a variety of neuropathic pain
behaviors. Here we characterized the degree to which chemokines/receptors are upregulated in
primary afferent neurons of the dorsal root ganglion (DRG) following chronic morphine
treatment and correlated these changes with hypernociceptive behavior in rodents. We
demonstrate that the chemokine, stromal-derived factor-1 (SDF-1/CXCL12) is upregulated in
sensory neurons of both the mouse and the rat. We also determined that there is pronounced
CXCR4 expression in both satellite glial cells and some sensory neurons of the DRG. Moreover,
intraperitoneal administration of the specific CXCR4 antagonist, AMD3100, completely
reversed OIH in the rat. Collectively, the data suggest that opioid-induced SDF-1/CXCR4
signaling is central to the development of OIH and that receptor antagonists represent a
promising novel approach to the management of the side effects associated with long term
opiates for chronic pain control.