Dexmedetomidine fails to cause hyperalgesia after cessation of chronic administration.
Hyperalgesia occurring after the cessation of chronic opioid administration occurs in humans and has been modeled in rodents with chronic systemic and intrathecal administration paradigms. It is, however, unclear if this type of postanalgesic hyperalgesia is unique to opioids. The alpha(2)-adrenergic receptor agonist, dexmedetomidine (Dex), is similar to opioids in that it is an analgesic that interacts with cell-surface receptors linked to the inhibition of adenylate cyclase and the modulation of ion channel activity. In these studies, we first constructed antinociceptive dose-response curves for Dex and morphine (MSO4). The 50% effective doses for Dex and MSO4 administered intraperitoneally to C57Bl/6 mice were 75 micro g/kg and 5.2 mg/kg, respectively. Using equally effective doses, we treated separate groups of mice with twice-daily injections of Dex or MSO4 for 5 days. Tolerance to these drugs was documented after this period. In the 16-72 h after cessation of administration, MSO4-treated mice demonstrated both thermal hyperalgesia and mechanical allodynia. However, the Dex-treated mice showed no changes in their thermal or mechanical withdrawal thresholds. We conclude that using this experimental paradigm, opioids but not an alpha(2)-adrenergic agonist, cause hyperalgesia and allodynia after cessation of chronic administration.


CONCLUSIONS
The cessation of the administration of opioids is associated with hyperalgesia in both humans and other animals. However, antinociceptive dexmedetomidine does not seem to be associated with this type of hyperalgesia syndrome during periods of abstinence.
Davies
M Frances
MF
Veterans Affairs Palo Alto Health Care System and Stanford University Department of Anesthesiology, California 94304, USA.
Haimor
Fawzi
F
Lighthall
Geoffrey
G
Clark
J David
JD
D000262:Adenylyl Cyclases / Q000502:physiology; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000009:adverse effects*; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D020927:Dexmedetomidine / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced* / Q000523:psychology; D007473:Ion Channels / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000494:pharmacology; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation; D013375:Substance Withdrawal Syndrome / Q000523:psychology*
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000701:Analgesics, Opioid; D007473:Ion Channels; D020927:Dexmedetomidine; D009020:Morphine; D000262:Adenylyl Cyclases