Fractalkine (Chemokine CX3C motif ligand 1) antibodies reduce neurogenic inflammation and pain perception in acute and chronic pancreatitis

Introduction In clinical practice the WHO´s pain therapy regime is almost insufficient for the treatment of acute (AP) and chronic pancreatitis (CP).

Aims To develop better pain therapy strategies, the impact of a promising new approach of CX3CL1 antibodies on neurogenic inflammation and pain perception was tested.

Methods Here, we performed a standardized measurement of the impact of fractalkine neutralizing monoclonal antibody treated adult male C57BL/6 (Black 6) mice on abdominal pain perception using the well-established von Frey test. Histopathomorphological impact on pancreas tissue and dorsal root ganglion of treated mice was represented by immunohistochemistry as well as determining clinical parameters.

Results Von Frey testing showed animals treated with FKN versus treatment with control IgG (DNP) result in an attenuation of pain perception in acute pancreatitis (FKN: 36.45±1.36 vs. DNP: 44.9±2.87, n=20, p< 0.0001). In chronic pancreatitis a highly significant reduction of pain perception could be measured after 4 weeks of treatment (FKN: 34.39±2.77 vs. DNP: 41.45±2.28, n=19, p< 0.0001). Histopathomorphological we were able to see a significant reduction of the “Spormann Score” in AP (DNP: 10.2±1.3 vs. FKN: 7.14±0.9, n=17, p= 0.0001) as well as in CP (DNP: 13.6±1.42 vs. FKN: 9.8±1.1, n=18, p< 0.0001), which means a lesser formation of edema, hemorrhagia, cell necrosis, vacuolization and inflammatory cell infiltration in the FKN antibody treated tissue. The cFos expression in the dorsal root ganglion of the spinal cord in treated animals were also significantly reduced in compare to untreated animals, which histologically confirms the pain measurements (AP: DNP:9.0±3.2 vs. FKN: 3.4±1.3, n=15, p=0.0005; CP: DNP: 5.7±2.3 vs. FKN: 2.4±0.9, n=9, p=0.0209).

Conclusion Targeting fractalkine via neutralizing antibodies reduces pain due to pancreatitis over neuronal suppression.

Publication History

Article published online:
07 September 2021