In vitro opioid induced proliferation of peripheral blood immune cells correlates with in vivo cold pressor pain tolerance in humans: a biological marker of pain tolerance.

There is substantial evidence for bidirectional communication between the immune system and the central nervous system, as the cells and signalling molecules of the immune system influence many central nervous system functions, for instance nociception. Opioids, such as morphine, produce analgesia and numerous other central and peripheral effects including sedation and euphoria, while their effects on the immune system are wide-ranging. There is considerable interindividual variability in basal nociception and response to opioids, however, the physiological and biological mechanisms underlying this are unclear. Therefore, we investigated the relationship between the immune system and basal nociceptive thresholds, using the proliferative response of isolated peripheral blood mononuclear cells and cold pressor pain tolerance. Here we show that the percent increase in proliferation of peripheral immune cells from 13 healthy subjects incubated with morphine ex vivo is highly correlated with the subjects' tolerance to noxious cold stimuli (Pearson r = 0.92, P < 0.0001). These pilot data provide evidence of a novel objective biological marker of pain tolerance in humans, which also links the immune and opioid systems with basal pain tolerance.