RT Journal Article
SR Electronic
T1 Early Nociceptive Events Influence the Temporal Profile, but not the Magnitude, of the Tonic Response to Subcutaneous Formalin: Effects with Remifentanil
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 876
OP 883
VO 280
IS 2
A1 Bradley K. Taylor
A1 M. Alex Peterson
A1 Allan I. Basbaum
YR 1997
UL http://jpet.aspetjournals.org/content/280/2/876.abstract
AB Injection of dilute formalin into the hindpaw produces brief (phase 1) and persistent (phase 2) nociceptive responses in the rat. We recently reported that ongoing peripheral nerve input is required for the expression of behavioral and cardiovascular responses during phase 2. Here we evaluated the contribution of central and peripheral sensitization mechanisms, generated during phase 1, to the magnitude and temporal profile of phase 2. During phase 1, we administered analgesic doses of an ultrashort-acting opioid, remifentanil (i.v. administration from 0–5 min after 5.0% formalin injection), or anesthetic concentrations of halothane (2.1%). Inhibition of phase 1 did not reduce the magnitude of flinching and cardiovascular responses during phase 2, but it did delay their onset and/or termination. Longer remifentanil infusions (0–15 or 0–30 min) produced even longer delays (up to 30 min) in the onset and termination of flinching during phase 2; however, when remifentanil was administered during the early part of phase 2 (15–30 or 15–45 min), it did not prolong the time to termination of phase 2. Continuous infusion (10 mg/kg/hr i.v.) of a peripherally acting opiate antagonist, naloxone methiodide, did not reduce the antinociception produced by remifentanil during phase 1 but almost completely reversed the delay in the onset and termination of phase 2. We conclude that central sensitization mechanisms during phase 1 do not influence the magnitude of phase 2. We also hypothesize that remifentanil interacts with peripheral opioid receptors to impede the formalin-evoked synthesis and/or release of proinflammatory compounds during phase 1 and thus delay phase 2. The American Society for Pharmacology and Experimental Therapeutics