Debilitating abdominal pain is a common symptom affecting most patients with chronic pancreatitis (CP). There are multiple underlying mechanisms that contribute to pain which makes successful treatment difficult. The identification of biomarkers for subtypes of pain could provide viable targets for non-opioid interventions and the development of mechanistic approaches to pain management in CP. Nineteen inflammation- and nociception-associated proteins were measured in serum collected from 358 subjects with definite CP enrolled in PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies (PROCEED), a prospective observational study of pancreatitis in US adult subjects. First, serum levels of putative biomarkers were compared between CP subjects with and without pain. Only PDGF-B stood out, with levels significantly higher in the CP pain group as compared to subjects with no pain. Subjects with pain were then stratified into four pain subtypes (Neuropathic, Nociceptive, Mixed and Unclassified). A comparison of putative biomarker concentration among five groups (No pain and 4 pain subtypes), identified unique proteins that were correlated with pain subtypes. Serum TGFβ1 level was significantly higher in the Nociceptive Pain group compared to the No Pain group, suggesting that TGFβ1 may be a biomarker for Nociceptive pain. The Neuropathic pain only group was too small to detect statistical differences. However, GP130, a co-receptor for IL-6, was significantly higher in the Mixed pain group compared to the groups lacking a neuropathic pain component. These data suggest that GP130 may be a biomarker for Neuropathic pain in CP. PERSPECTIVE: Serum TGFβ1 and GP130 may be biomarkers for nociceptive and neuropathic CP pain, respectively. Preclinical data suggest inhibiting TGFβ1 or GP130 reduces CP pain in rodent models, indicating that additional translational and clinical studies may be warranted to develop a precision medicine approach to the management of pain in CP.