Topic:
4.6 Pharmacological Therapies
2nd Topic:
1.7 Central Neuropathic Pain
Title:
IMPORTANCE OF CCL17/CCL22/CCR4 SIGNALING IN NOCICEPTIVE TRANSMISSION AND MORPHINE ANALGESIC POTENCY IN NAÏVE AND NEUROPATHIC ANIMALS
Author(s):
J. Kujacz1, K. Popiołek-Barczyk1, W. Makuch1, A. Ciechanowska1, J. Dobrogowski2, A. Przeklasa- Muszyńska2, J. Mika1
Institute(s):
1Institiute of Pharmacology Polish Academy of Sciences, Pharmacology of Pain, Krakow, Poland, 2Jagiellonian University Medical College, Department of Pain Research and Treatment, Chair of Anesthesiology and Intensive Therapy, Krakow, Poland
Text:
Background and aims: Current investigations underline the chemokine signaling pathways in the development of neuropathy, however, the role of CCR4 was not study so far. We examined the role of CCR4 and its ligands (CCL17, CCL22) on the development of hypersensitivity and morphine effectiveness in naïve and neuropathic animals. 
Methods: The Chronic Constriction Injury (CCI) model of neuropathic pain in rats was used. Single and/or repeated, intrathecal injections of C021 (CCR4 antagonist) and/or morphine were performed and pain behavior was evaluated by von Frey/cold plate tests. Changes in proteins levels were analyzed by Western blot. The influence of single, intrathecal injection of CCL17 and CCL22 in naïve mice on pain development was investigated.
Results: We demonstrated that administration of CCL17 and CCL22 induces pain-related behavior in naive animals. Administration of the C021 (16h and 1h before CCI and then once daily for 8 days after injury) diminished hypersensitivity and enhanced the analgesic properties of morphine. C021 reduced Iba1-positive cells activation, but not GFAP, CD4 and CD8 in spinal cord and DRG. C021 diminished the level of pronociceptive IL-1beta and IL-18 in both structures, while the level of antinociceptive IL-10 was reduced only in DRG and IL-6 was not affected.
Conclusions: Our research suggest that CCL17/CCL22/CCR4 signaling pathway may be a potential therapeutic target for the treatment of neuropathy.
Acknowledgments: Supported by National Science Centre, Poland (OPUS 2016/21/B/NZ4/00128) and by statutory funds of the Department of Pain Pharmacology, Institute of Pharmacology PAS. Joanna Kujacz acknowledges the support of InterDokMed project no.POWR.03.02.00-00-I013/16.