TY - JOUR
T1 - Morphine priming in rats with chronic inflammation reveals a dichotomy between antihyperalgesic and antinociceptive properties of deltorphin
AU - Gendron, L.
AU - Esdaile, M. J.
AU - Mennicken, F.
AU - Pan, H.
AU - O'Donnell, D.
AU - Vincent, J. P.
AU - Devi, L. A.
AU - Cahill, C. M.
AU - Stroh, T.
AU - Beaudet, A.
N1 - Funding Information:
This work was supported by grants MOP-38014 and MOP-66986 from the Canadian Institutes for Health Research (CIHR) to A.B. and C.M.C., respectively, and by grant from AstraZeneca Canada Inc. L.G. was funded by fellowship MFE-63497 from the Canadian Institutes of Health Research (CIHR). The authors thank Clélia Tommi, Mariette Lavallée, and Shannon Parker for their technical assistance and Claude Roberge for her expert help in the design of real-time PCR primers. This work was presented in part at the Society for Neuroscience’s meeting 2004, in San Diego, CA, USA: L. Gendron, A.-L. Lucido, F. Mennicken, D. O’Donnell, T. Stroh and A. Beaudet. Increased delta opioid receptor internalization in rat dorsal root ganglia following prolonged morphine treatment or chronic inflammatory pain. Program No. 406.5 2004 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience, 2004. Online.
PY - 2007/1/5
Y1 - 2007/1/5
N2 - We previously showed that prolonged morphine treatment and chronic inflammation both enhanced delta opioid receptor (δOR) cell surface density in lumbar spinal cord neurons. Here, we sought to determine whether administration of morphine to rats with chronic inflammation would further increase the bio-availability of δOR, and thereby the analgesic properties of the δOR agonist deltorphin, over that produced by inflammation alone. We found that chronic inflammation produced by injection of complete Freund's adjuvant (CFA) into the hind paw resulted in a bilateral increase in the binding and internalization of fluorescent deltorphin in neurons of the lumbar spinal cord as did prolonged morphine treatment [Morinville A, Cahill CM, Aibak H, Rymar VV, Pradhan A, Hoffert C, Mennicken F, Stroh T, Sadikot AF, O'Donnell D, Clarke PB, Collier B, Henry JL, Vincent JP, Beaudet A (2004a) Morphine-induced changes in delta opioid receptor trafficking are linked to somatosensory processing in the rat spinal cord. J Neurosci 24:5549-5559]. This effect was accompanied by an increase in the antinociceptive efficacy of intrathecal deltorphin as measured using the tail-flick test. Treatment of CFA-injected rats with morphine decreased the cell surface availability of δOR in neurons of the dorsal horn of the lumbar spinal cord as compared with treatment with CFA alone. Behaviorally, it significantly enhanced the antihyperalgesic effects of deltorphin (plantar test; % maximum possible antihyperalgesic effect (MPAHE)=113.5%±32.4% versus 26.1%±11.6% in rats injected with CFA alone) but strongly reduced the antinociceptive efficacy of the drug (tail-flick test; % maximum possible antinociceptive effect (MPE)=29.6%±3.6% versus 66.6%±6.3% in rats injected with CFA alone) suggesting that the latter, but not the former, is linked to the δOR trafficking events observed neuroanatomically. These results demonstrate that in chronic inflammation, the antihyperalgesic effects of δOR agonists may be enhanced by morphine pre-treatment. They also reveal a dichotomy between mechanisms underlying antihyperalgesic and antinociceptive effects of δOR agonists.
AB - We previously showed that prolonged morphine treatment and chronic inflammation both enhanced delta opioid receptor (δOR) cell surface density in lumbar spinal cord neurons. Here, we sought to determine whether administration of morphine to rats with chronic inflammation would further increase the bio-availability of δOR, and thereby the analgesic properties of the δOR agonist deltorphin, over that produced by inflammation alone. We found that chronic inflammation produced by injection of complete Freund's adjuvant (CFA) into the hind paw resulted in a bilateral increase in the binding and internalization of fluorescent deltorphin in neurons of the lumbar spinal cord as did prolonged morphine treatment [Morinville A, Cahill CM, Aibak H, Rymar VV, Pradhan A, Hoffert C, Mennicken F, Stroh T, Sadikot AF, O'Donnell D, Clarke PB, Collier B, Henry JL, Vincent JP, Beaudet A (2004a) Morphine-induced changes in delta opioid receptor trafficking are linked to somatosensory processing in the rat spinal cord. J Neurosci 24:5549-5559]. This effect was accompanied by an increase in the antinociceptive efficacy of intrathecal deltorphin as measured using the tail-flick test. Treatment of CFA-injected rats with morphine decreased the cell surface availability of δOR in neurons of the dorsal horn of the lumbar spinal cord as compared with treatment with CFA alone. Behaviorally, it significantly enhanced the antihyperalgesic effects of deltorphin (plantar test; % maximum possible antihyperalgesic effect (MPAHE)=113.5%±32.4% versus 26.1%±11.6% in rats injected with CFA alone) but strongly reduced the antinociceptive efficacy of the drug (tail-flick test; % maximum possible antinociceptive effect (MPE)=29.6%±3.6% versus 66.6%±6.3% in rats injected with CFA alone) suggesting that the latter, but not the former, is linked to the δOR trafficking events observed neuroanatomically. These results demonstrate that in chronic inflammation, the antihyperalgesic effects of δOR agonists may be enhanced by morphine pre-treatment. They also reveal a dichotomy between mechanisms underlying antihyperalgesic and antinociceptive effects of δOR agonists.
KW - antihyperalgesia
KW - antinociception
KW - chronic inflammation
KW - delta opioid receptor
KW - deltorphin
KW - tolerance
UR - https://www.scopus.com/pages/publications/33751520246
U2 - 10.1016/j.neuroscience.2006.08.077
DO - 10.1016/j.neuroscience.2006.08.077
M3 - Article
C2 - 17055663
AN - SCOPUS:33751520246
SN - 0306-4522
VL - 144
SP - 263
EP - 274
JO - Neuroscience
JF - Neuroscience
IS - 1
ER -