Systemic opioids do not suppress spinal sensitization after subcutaneous formalin in rats

Preemptive treatment with a combination of inhalation anesthesia plus intrathecal morphine has been shown to inhibit development of hyperalgesia that follows subcutaneous (SC) formalin injection in rats. Using a similar paradigm, this study sought to determine whether moderate doses of opioids, administered systemically, could inhibit development of a hyperalgesic state.

Flinches per minute were observed 1 and 5 min after formalin injection (phase 1) and at 5-min intervals for the remainder of 1 h (phase 2) for five groups of rats. All animals received isoflurane 1% during and for 6 min after formalin injection. Groups 1 and 2 received SC alfentanil 200 micrograms/kg or normal saline, respectively, before formalin and 0.5 mg/kg naloxone SC 6 min after formalin. Groups 3 and 4 received SC morphine 20 mg/kg or SC normal saline, respectively, before formalin and SC naloxone 0.5 mg/kg plus naltrexone 0.5 mg/kg after formalin. Group 5 received normal saline at both injection times.

Phase 2 activity was nearly identical for the three control groups. Total phase 2 activity for group 1 (alfentanil) was 16% less than control (not significant, P > 0.05). Total phase 2 activity for group 3 (morphine) was almost identical to control.

Administration of 1% isoflurane plus systemic opioids, administered in doses that produce profound analgesia in standard analgesic testing paradigms, do not produce the significant suppression of subsequent hyperalgesia that has been reported with inhalation anesthesia plus intrathecal opioids.