These responses were further reduced with the highest concentration tested, 20 mg/kg, although the interpretation of these effects are complicated by the dramatic hypothermia produced at this dosage. It is important to note that the PBMC-treated scores did not drop to the level of TRPM8-/- mice , indicating partial blockade of the channel at this dose. Interestingly, we observed individual differences in the amplitude of the score reduction with 10 mg/kg PBMC under normal conditions, which may suggest that, at this low dose, individual variations in physiology may affect drug action. However, due to the thermoregulatory effects described above, we were limited in the amount of drug we could administer to the mice without potentially confounding thermosensory responses. TRPM8 has also been implicated in the painful cold hypersensitivity that is a distressing symptom of inflammatory and neuropathic conditions, as well as platinum-based chemotherapy drugs . It would therefore be greatly beneficial to both chronic pain and chemotherapy patients to have a drug which could control such symptoms. Thus we tested whether PBMC could reduce the behavioral responses to evaporative cooling in models of inflammatory and neuropathic pain. In the CFA model of inflammatory pain and the CCI model of neuropathic pain, we saw a reduction in the response scores of mice treated with 10 mg/kg PBMC. Interestingly, both of these reduced scores remained higher than those seen at Paclitaxel structure baseline or with TRPM8-/- mice, again BAY-60-7550 supplier suggesting that at this dose PBMC only partially blocked TRPM8 function in vivo. However, given that the aim of a good symptom-controlling drug would be to reduce the hypersensitivity to cold without abolishing normal thermosensation , this may not be a completely undesirable effect. In contrast, when we examined oxaliplatin-treated animals given PBMC, we did not see a statistically significant reduction in response scores. It is puzzling that PBMC would be effective against one model of neuropathic pain but not another. There are two probable explanations for this observation: First, it is possible that other mechanisms may also be involved in cold hypersensitivity in oxaliplatin-induced neuropathy and PBMC is ineffective against these mechanisms , although our and others�� recent evidence suggests that TRPM8 plays a pivotal role in this pathology .