Nitrous oxide or halothane, or both, fail to suppress c-fos expression in rat spinal cord dorsal horn neurones after subcutaneous formalin

Abstract

In rats injected s.c. with formalin, behavioural correlates of the amount and pattern of Fos-like immunoreactivity (Fos-LI) (molecular responses to pain) were studied to test if early phase treatment with 75% nitrous oxide or 2% halothane, or both, suppressed subsequent spinal sensitization. Rats were allocated to four treatment groups: (1) 100% oxygen (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% halothane (1.5 MAC, n = 18) for 20 min. Each rat then received a s.c. injection of 1% formalin 50 μl into the left hindpaw and anaesthesia was maintained for another 5 min (early phase). A fifth group of rats receiving fentanyl 100 μg kg-1 (n=12) before formalin injection were studied taneously 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 compared according to laminar distribution. Formalin-induced behavioural hyperalgesia during the early phase was suppressed completely by fentanyl, 75% nitrous oxide, or 2% halothane, or both. The late phase response was attenuated by all four anaesthetic regimens within 20 min after injection, whereas behavioural scores for the nitrous oxide, halothane, or both, groups were nearly identical to the control 20 min later. Fentanyl suppressed the late phase response until 30 min after formalin 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 neck of the dorsal horn (44.9% of control, P < 0.01) and also in the nucleus 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 stimulation. This result supports the previous hypothesis that inhalation anaesthesia lacks pre-emptive analgesic action. Inhalation anaesthetic agents, unlike fentanyl, suppress the early and late phase response because of anaesthetic but not analgesic effects. Thus, we suggest that measuring the genetic product of c-fos proto-oncogene is a useful adjunct to pharmacological tests whenever behavioural hyperalgesia is questionable or unobtainable.