Changes in plasma or cerebro-spinal fluid (CSF) levels of biochemical substances (other than corticosteroids) have been measured experimentally in attempts to find useful indices of pain. These substances include neurotransmitters, enzymes, neuro-modulators, cytokines, acute phase proteins, other hormones. As yet, evidence that any of these provide practical indices is not available.
Energy Reserves and Metabolites
Changes in plasma concentrations of glucose, free fatty acids, lactic acid and other substances occur in response to stress and / or prolonged activity seen after some types of pain. None of these parameters have been shown to be a specific index for pain (Peers et al 2002). Both production and use or elimination of the parameter by the body needs to be taken into account.
Only small amounts of intracellular enzymes are normally present in blood plasma. However, enzymes leak from damaged organs, and their activity in the blood increases. Increases occur in the plasma activities of muscle and liver enzymes e.g. creatine kinase with azoturia and sorbitol dehydrogenase, with ragwort poisoning. However, no systematic relationship has been demonstrated between changes in plasma enzyme activities and established assessments of pain.
Acute phase proteins (APP)
Acute phase proteins are produced mainly by the liver in response to infection, inflammation and tissue damage, though they may also be increased by starvation, during pregnancy and by some stressful situations. There are many different APPs including fibrinogen, haptoglobin, C-reactive Protein (CRP) and Serum Amyloid A (SAA). The diagnostic importance of each APP varies with species (Kent 1992; Gruys et al 1994; Eckersall 2000), the time course of the disease and the causal agent. They are increased in some painful conditions e.g. clinical mastitis (Eckersall et al 2001) and after surgical castration in horses (Pepys et al 1989; Kent & Goodall 1991), and cattle (Fisher et al 1997, 2001; Earley & Crowe 2002). However, APPs did not increase during the acute response to rubber ring castration in lambs (Price & Nolan, 2001).
Bradykinin increased in cow's milk in association with mastitis, a painful inflammatory condition (Eshraghi et al 1999).
Prostaglandins are also increased in mastitis, which is associated with a lowering of the threshold to a mechanical stimulus (hyperalgesia) (Dolan et al 2000).
Substance P, a neuro-peptide, was measured in plasma immediately after rubber ring castration with inconclusive results (J. Barker, personal communication). In addition, no significant changes were found in either CSF or plasma concentrations of Substance P, Neurokinin A or Dynorphin during the chronic response (0 to 52 days after treatment) to rubber ring castration despite changes in behaviour suggestive of chronic inflammatory pain (Kent et al 1999).