Mu and Delta Opioid Receptor Targeting Reduces Connexin 43-Based Heterocellular Coupling during Neuropathic Pain

International Journal of Molecular Sciences

Daniele Tibullo¹  Giovanni Li Volti¹  Agostino Marrazzo²  Lorella Pasquinucci²  Rita Turnaturi²  Salvatore Spoto³  Carmela Parenti³  Santina Chiechio³  Nunzio Vicario⁴  Agata Zappalà⁴  Rosalba Parenti⁴  Lucia Longhitano⁴  Simona Denaro⁴  Federica Maria Spitale⁴ 

[1] Section of Biochemistry, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy;Section of Medicinal Chemistry, Department of Drug and Health Sciences, University of Catania, 95123 Catania, Italy;Section of Pharmacology and Toxicology, Department of Drug and Health Sciences, University of Catania, 95123 Catania, Italy;Section of Physiology, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy;

关键词: chronic constriction injury;    microglia;    astrocyte;    MOR;    DOR;    inflammation;   

DOI  :  10.3390/ijms23115864

来源: DOAJ

【 摘 要 】

Chronic neuropathic pain emerges from either central or peripheral lesions inducing spontaneous or amplified responses to non-noxious stimuli. Despite different pharmacological approaches to treat such a chronic disease, neuropathic pain still represents an unmet clinical need, due to long-term therapeutic regimens and severe side effects that limit application of currently available drugs. A critical phenomenon involved in central sensitization is the exchange of signalling molecules and cytokines, between glia and neurons, driving the chronicization process. Herein, using a chronic constriction injury (CCI) model of neuropathic pain, we evaluated the efficacy of the mu (M-) and delta (D-) opioid receptor (-OR) targeting agent LP2 in modulating connexin-based heterocellular coupling and cytokine levels. We found that long-term efficacy of LP2 is consequent to MOR-DOR targeting resulting in the reduction of CCI-induced astrocyte-to-microglia heterocellular coupling mediated by connexin 43. We also found that single targeting of DOR reduces TNF and IL-6 levels in the chronic phase of the disease, but the peripheral and central discharge as the primary source of excitotoxic stimulation in the spinal cord requires a simultaneous MOR-DOR targeting to reduce CCI-induced neuropathic pain.

【 授权许可】

Unknown