Development of molecular and cellular biomarkers of pain.

Observation of physiologic and behavioral responses is the main method used to assess pain in people and animals. These approaches are often difficult to objectively measure in laboratory rodents and provide no insight into associated molecular and cellular changes in the organism. To identify CNS markers for pain, we analyzed the gene expression profiles of midbrain sections of mice that had experienced either adjuvant injections in the footpad or partial sciatic nerve ligation (PSL), which are recognized models of inflammatory and neuropathic pain, respectively. The potential for pain-associated factors to be present in the blood and to affect other tissues was analyzed by monitoring the growth of various cell lines that were exposed to serum from these mice and to plasma from rats experiencing surgical pain and their respective controls. Adjuvant injection increased the transcription of 12 genes and decreased that of 38 genes by at least 2-fold, whereas PSL increased the transcription of 2 genes and decreased that of 23, with no overlap. Serum from mice with PSL stimulated the growth of the rat mammary tumor cell line RMT50. Similarly, plasma collected from rats after a painful surgical procedure promoted the growth of RMT50 and MDA-MB-235 cells. These results demonstrate that the gene expression profiles of brain tissue from mice exposed to painful stimuli vary depending on the nature of the stimulus, and that the growth of some mammary tumor cell lines can be affected by blood collected from rodents exposed to these stimuli.