1. BIOMARKERS mRNA expression of Immune Receptors – Interleukins 6 & 10 (IL6, IL10) – Tumor Necrosis Factor –alpha (TNF) Adrenergic Receptors – Alpha 2 – Beta 1 – Beta 2 – Catechol-O-methyl transferase (COMT) Metabolic Receptors (sense heat, acid) – Acid sensitive ion channel (ASIC3) – Purinergic receptors (P2X4 and P2X5) – Transient receptor Potential Vanilloid Type 1 (TRPV1) Opioid Receptors NMDA Receptors

2. Immune Opioid/NMDA Adrenergic Metabolic Nerve Ending IL6CD14 IL10 TNF ASIC3 P2X4 TRPV1 P2X5 Beta1 Beta2 Alpha2 COMT FQKappa Delta NMDA Mu

3. The Link mRNA expression in Leukocytes

4. Peripheral Marker Hypothesis mRNA expression in Leukocytes Receptor Expression on WBC may mirror expression – Central & Peripheral Nervous System WBC’s respond to stimuli – Adrenergic, metabolic, etc Easily Obtained

5. WBC