Acute non-traumatic pain increases the hepatic amino- to urea-N conversion in normal man.
OBJECTIVE
Severe stress results in a catabolic state with nitrogen (N) loss via hepatic urea synthesis, and in most situations a sensation of pain. Our purpose was to establish whether pain per se upregulates liver function as to urea synthesis.


METHODS
Ten healthy male volunteers were investigated on 3 occasions in a crossover design. Self-controlled electrical pain was applied to the abdominal skin for 30 min to an intensity of 8 on a visual analogue scale from 0 to 10. Next, the electric profile was reproduced during local analgesia (mepivacaine 2.5 mg/kg bw), and the pain was scored to only 0.5. Finally, there was a control experiment with no intervention. Alanine infusion (1 mmol/kg/h) was started 2 h before intervention and continued throughout the investigation. Urea-N synthesis rate (UNSR) was estimated hourly as urinary excretion corrected for accumulation in body water and gut hydrolysis.


RESULTS
Pain increased the Functional Hepatic Nitrogen Clearance (FHNC) assessed by the ratio UNSR/AAN (in the 3 h following pain) by 20% (22.7+/-1.2 vs 19.0+/-0.7 l/h (control), p<0.05). FHNC during local analgesia was in between (21.1+/-1.1 l/h) but not significantly different from either of the two other experiments. Mean blood amino-N concentration (AAN) and mean UNSR were comparable in the three situations. There was no difference in serum glucagon among experiments, but pain increased serum cortisol (452+/-15 vs 233+/-20 nmol/l (control), p<0.001) and plasma adrenaline (104+/-16 vs 58+/-9 pg/ml (control), p<0.05).


CONCLUSIONS
Acute, severe atraumatic pain induces an increase in the ability of the liver to convert amino- to urea-N, and thus acts as a catabolic stimulus via regulation of liver function. The measurements of known endocrine regulators of urea synthesis do not explain the phenomenon. The present data, however, suggest the hypothesis that the effects of pain were attenuated by local analgesia. If this is confirmed by further experiments, it would indicate a signal transmission to the liver which has not been previously described.
Greisen
J
J
Department of Medicine V, Aarhus University Hospital, Denmark.
Grøfte
T
T
Hansen
P O
PO
Jensen
T S
TS
Vilstrup
H
H
D000208:Acute Disease; D000328:Adult; D000596:Amino Acids / Q000378:metabolism*; D000779:Anesthetics, Local / Q000494:pharmacology; D018592:Cross-Over Studies; D004558:Electric Stimulation; D004837:Epinephrine / Q000097:blood; D006728:Hormones / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008297:Male; D008619:Mepivacaine / Q000494:pharmacology; D009584:Nitrogen / Q000378:metabolism*; D009638:Norepinephrine / Q000097:blood; D010146:Pain / Q000097:blood / Q000209:etiology / Q000378:metabolism*; D012016:Reference Values; D014508:Urea / Q000378:metabolism*
D000596:Amino Acids; D000779:Anesthetics, Local; D006728:Hormones; D014508:Urea; D008619:Mepivacaine; D009584:Nitrogen; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine