NITROUS-OXIDE OR HALOTHANE, OR BOTH, FAIL TO SUPPRESS C-FOS EXPRESSION IN RAT SPINAL-CORD DORSAL HORN NEURONS AFTER SUBCUTANEOUS FORMALIN

In rats injected s.c. with formalin, behavioural correlates of the amo unt and pattern of Fos-like immunoreactivity (Fos-LI) (molecular respo nses to pain) were studied to test if early phase treatment with 75% n itrous oxide or 2% halothane, or both, suppressed subsequent spinal se nsitization. Rats were allocated to four treatment groups: (1) 100% ox ygen (control, n = 15), (2) 75% nitrous oxide (0.5 MAC, n = 12), (3) 2 % halothane (1 MAC, n = 12), and (4) 75% nitrous oxide with 2% halotha ne (1.5 MAC, n = 18) for 20 min. Each rat then received a s.c. injecti on of 1% formalin 50 mu l into the left hindpaw and anaesthesia was ma intained for another 5 min (early phase). A fifth group of rats receiv ing fentanyl 100 mu g kg(-1) (n = 12) 10 min before formalin injection were studied simultaneously as a positive control. Rats in all groups were killed 60 min after formalin injection and maximal counts of Fos -LI labelled neurones in the dorsal horn of the rat spinal cord were c ompared according to laminar distribution. Formalin-induced behavioura l hyperalgesia during the early phase was suppressed completely by fen tanyl, 75% nitrous oxide, or 2% halothane, or both. The late phase res ponse was attenuated by all four anaesthetic regimens within 20 min af ter injection, whereas behavioural scores for the nitrous oxide, halot hane, or both, groups were nearly identical to the control 20 min late r. Fentanyl suppressed the late phase response until 30 min after form alin injection but failed to reduce it thereafter. The numbers of Fos- LI labelled neurones for groups given nitrous oxide, or halothane, or both, were identical to the control, whereas numbers for fentanyl were 47.2% less (P < 0.01). The decrease occurred predominantly in the nec k of the dorsal horn (44.9% of control, P < 0.01) and also in the nucl eus proprius and superficial laminae (54.4% and 56.2% of control, P < 0.05). In summary, we found that nitrous oxide, or halothane, or both, did not suppress subsequent spinal sensitization to noxious stimulati on. This result supports the previous hypothesis that inhalation anaes thesia lacks pre-emptive analgesic action. Inhalation anaesthetic agen ts, unlike fentanyl, suppress the early and late phase response becaus e of anaesthetic but not analgesic effects. Thus, we suggest that meas uring the genetic product of c-fos proto-oncogene is a useful adjunct to pharmacological tests whenever behavioural hyperalgesia is question able or unobtainable.