Morphine, But Not Inhalation Anesthesia, Blocks Post-injury Facilitation The Role of Preemptive Suppression of Afferent Transmission

Abstract

The subcutaneous injection of formalin in the rat paw results in several minutes of flinching (phase 1) followed by cessation of activity then resumption of flinching (phase 2), which depends on facilitation of spinal transmission evoked by C-fiber activity generated immediately after the noxious stimulus. It was hypothesized that suppression of dorsal horn activity during and immediately after formalin injection by inhalation anesthetics or intrathecal opiates would block spinal facilitation and inhibit phase 2 flinching, even if the anesthetic or opiate were eliminated before phase 2. Flinches/min were observed 1 and 5 min after formalin injection (phase 1) and at 5-min intervals thereafter for 60 min (phase 2) for five groups of rats: control (group 1); 1% isoflurane before and for 6 min after formalin (group 2); 2.5% isoflurane before and for 6 min after formalin (group 3); 1% isoflurane and 70% N2O before and for 6 min after the formalin (group 4); and 30 micrograms intrathecal morphine given 20 min before formalin and 30 micrograms intrathecal naloxone given 6 min after formalin, combined with 1% isoflurane as in group 2 (group 5). All groups, except control, exhibited essentially complete suppression of phase 1 flinching. The changes in phase 2 flinching, expressed as a percent of total phase 2 flinches for the control animals, were: control (100%) = group 4 (109 +/- 17%) > group 2 (66 +/- 13%) = group 3 (66 +/- 14%) > group 5 (19 +/- 12%). Isoflurane, even at high concentrations, administered during and shortly after a noxious stimulus produces only a modest reduction in facilitation of afferent processing. The addition of intrathecal morphine during the period of nociceptor activity results in marked attenuation of the facilitated state.