Studies in~a new pain control by spinorphin, an endogenous factor : Changes in level of spinorphin and dipeptidyl peptidase III in cerebrospinal fluid from patients with pain

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Spinorphin (LVVYPWT), an endogenous bioactive peptide purified from the spinal cord, demonstrates a nociceptive effect on bradykinin-induced pain in the rat and inhibitory activity against carrageenan-induced neutrophil accumulation in the mouse model of acute inflammation. To further clarify its physiological role in pain and inflammation, we established a method to quantify spinorphin in human cerebrospinal fluid (CSE) and analyzed the relation between its level and the physiological state. First, a specific and sensitive competitive enzyme immunoassay (EIA) was developed with an anti-rabbit spinorphin antibody. Cross-reactivity of the specific antibody with spinorphin analogues was not significant, suggesting that the EIA was specific to spinorphin. Next, levels of spinorphin measured in CSFs derived from patients with various types of pain other than cancer pain were higher in the pain group than in the controls (patients with pain-free and noninflammatory disease of the central nervous system) (21.4±8.2 ng/ml, n=48 vs 8.61±4.4 ng/ml, n=28,P<0.05). Furthermore, the activity of several spinorphin-processing enzymes that regulate some types of pain was examined. The activity of dipeptidyl peptidase III (DPPIII) in CSFs of the pain group was lower than that in the control (1.40±0.65 vs 2.05±0.88 pmol/30 min/100μ1,P<0.05). Interestingly, a statistical correlation was observed between the increase of spinorphin levels and the decrease of DPPIII (r=-0.514,P<0.05). These results indicate that the level of spinorphin may, through the regulatory effect of enzymes, be an indicator of the pathophysiological state.