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Cerebrospinal Fluid Concentrations of Substance P and (Met)Enkephalin-ARG⁶-PHE⁷ during Surgery and Patient-controlled Analgesia

Departments of Anesthesiology and Hospital Pharmacy, University Hospital, Uppsala and Department of Pharmacology, University of Uppsala, Sweden.

Abstract

The possible role of two neuropeptides (substance P and (Met)enkephalin-Arg⁶-Phe⁷) in nociception were studied in 14 surgical patients. Lumbar cerebrospinal fluid (CSF) concentrations of the putative excitatory afferent transmitter substance P and the µ and receptor agonist (Met)enkephalin-Arg⁶-Phe⁷ were measured during general anesthesia for abdominal surgery and during the postoperative period when patient-controlled analgesia (PCA) was used for control of pain. The CSF ions sampled through an intrathecal catheter. Seven of the patients were randomly assigned to receive neurolept anesthesia; the rest were given isoflurane anesthesia without narcotics. No statistically significant changes occurred in substance P concentrations in CSF during surgery or postoperative PCA, nor were there significant differences between the two groups. There was, however, a significant correlation between CSF substance P concentrations before the start of PCA and pain assessment on a visual analogue scale. The individual changes in substance P concentrations during PCA was also inversely correlated to the consumption of medicine. The CSF (Met)enkephalin-Arg⁶-Phe⁷ concentrations were below the level of detection in seven of the patients before anesthesia. A large interindividual variability in both substance P and (Met)enkephalin-Arg⁶-Phe⁷ concentrations was evident. The absence of major changes in CSF neuro-peptide concentrations urns unexpected. Apparently inter-individual variations in neuropeptide output are considerable.

Key Words: PAIN, postoperative. • SPINAL CORD, cerebrospinal fluid. • POLYPEPTIDES, substance P, (met)enkephalin.