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Oral Pain Experience and TNF&alpha Salivary and Plasma Expression in Hematopoietic Stem Cell Transplantation Oncology Patients: A Pilot Study

Jane Fall-Dickson, RN, PhD1, Edward Ramsay, BS2, Claude Sportes, MD3, Kathleen Castro, RN, MSN4, and Patricia Woltz, RN, MSN1. (1) Mucosal Injury Unit, National Institute of Nursing Research, 10 Center Drive 10CRC 1339, Bethesda, MD 20892, (2) Symptom Management Laboratory, National Institute of Nursing Research, 10CRC 2N-104, Bethesda, MD 20892, (3) Experimental Transplantation and Immunology Branch, National Cancer Institute, 10CRC 4-3142, Bethesda, MD 20892, (4) Nursing Department, Hatfield Clinical Research Center, 10-CRC 3-2409 10 Center Drive, Bethesda, MD 20892

Stomatitis-related oropharyngeal pain contributes to morbidity in hematopoietic stem cell transplantation (HSCT) patients. We report results of a pilot study for a stomatitis intervention trial including effectiveness of opioids to manage oropharyngeal pain, and laboratory techniques to measure TNFα concentrations in plasma and salivary cell pellets. Multiple dimensions of pain were assessed pre- and 9 days post conditioning chemotherapy (CT) regimens using the Oral Mucositis Assessment Scale and Painometer". Plasma TNFα concentrations were measured (N = 23) using ELISA (ELISA; R&D Systems, Inc., Minneapolis, MN). Salivary cell pellet samples (N = 12) were processed via centrifugation, and RNA extracted using RNeasy kit (Qiagen #74104). Adult male and female subjects (N = 24) were enrolled in one of five HSCT protocols. Post-HSCT stomatitis was observed in 19 subjects (mean = 5.38). Subjects (n = 9) reported primarily continuous, mild overall intensity of oral pain (mean = 1.4), with higher pain levels with swallowing (n = 10) (mean = 2.4; range = 0 to 10). Subjects received opioids including hydromorphone (2-15.6 mg), morphine (11-19 mg), and oxycodone (2.50-50 mg) for oral pain. Eight subjects reported pain VAS scores greater than 3 (range = 3.2-10) while receiving opioids. TNFα plasma concentrations did not correlate significantly with stomatitis severity or oropharyngeal pain level. Salivary cell pellets yielded only traces of isolated RNA. Deficiencies in column-based RNA isolation methods may be similar to our previous results with low molecular weight RNA isolated from buccal brush cells via column-based versus solvent-based reagents. Lower numbers of salivary shed cells relative to buccal brushings; the presence of mucins and other heavily glycosylated proteins may contribute to scarce salivary RNA processed via columns. The poorly controlled oropharyngeal pain in post-HSCT patients despite individualized opioid treatment demonstrate this symptom remains a treatment challenge that may benefit from additional therapeutic strategies.