THE EFFECT OF MORPHINE ON FORMALIN-EVOKED BEHAVIOR AND SPINAL RELEASEOF EXCITATORY AMINO-ACIDS AND PROSTAGLANDIN E(2) USING MICRODIALYSIS IN CONSCIOUS RATS

1 In the present study, the object was to examine the effects of morph ine on spinal release in vivo of excitatory amino acids (EAA), prostag landin E(2) (PGE(2)), and a marker for nitric oxide (NO) synthesis, ci trulline (Cit), evoked by a protracted noxious stimulus produced by th e injection of formalin into the paw. Spinal release was monitored in conscious rats using a microdialysis probe implanted into the subarach noid space with the active site placed at the level of the lumbar enla rgement. In split dialysate samples, EAAs were measured by high perfor mance liquid chromatography (h.p.l.c.) and PGE(2) was determined by ra dioimmunoassay. 2 Resting concentrations in nmol ml(-1) for the amino acids (mean +/- s.e.mean, n = 21) were: 4.8 +/- 0.4 for glutamate (Glu ), 0.8 +/- 0.1 for aspartate (Asp), 8.8 +/- 0.8 for taurine (Tau), 24 +/- 3 for glycine (Gly), 19 +/- 3 for serine (Ser), 5.2 +/- 0.8 for as paragine (Asn), 64 +/- 4 for glutamine (Gln) and 5.2 +/- 0.4 for Cit. Mean basal release for PGE(2) was 12 +/- 1 pmol ml(-1). 3 Subcutaneous (s.c.) injection of 5% formalin evoked a biphasic flinching behaviour (phase 1: 0-9 min and phase 2: 10-60 min) of the injected paw. Corres ponding to phase 1 behaviour, there was a significant increase (50-100 %) in spinal levels of Glu, Asp, Tau, Gly, Cit and PGE(2), but not Ser , Asn and Gln. A significant (P<0.01) second phase increase in release was observed only for Cit and PGE(2). However, Glu and Asp levels wer e increased by approximately 45%. 4 Injection of morphine sulphate (3 mg kg(-1), s.c.) had no effect on resting release, but produced a sign ificant suppression of the formalin-evoked behaviour and release of Gl u, Asp, Tau, Gly, Cit and PGE(2). The effect of morphine was reversed by pretreatment with 1 mg kg(-1) naloxone. Naloxone by itself did not change the release or behaviour of the formalin test. 5 This study dem onstrates that both spinal EAA and PGE(2) release patterns correlate w ith behavioural nociceptive responses in the formalin test and that mo rphine suppresses the formalin-evoked behaviours and spinal release. T he reversal by naloxone of the morphine effect indicates mediation via an opioid receptor.