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- Title
Mu and Delta Opioid Receptor Targeting Reduces Connexin 43-Based Heterocellular Coupling during Neuropathic Pain.
- Authors
Vicario, Nunzio; Denaro, Simona; Turnaturi, Rita; Longhitano, Lucia; Spitale, Federica Maria; Spoto, Salvatore; Marrazzo, Agostino; Zappalà, Agata; Tibullo, Daniele; Li Volti, Giovanni; Chiechio, Santina; Pasquinucci, Lorella; Parenti, Rosalba; Parenti, Carmela
- Abstract
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.
- Publication
International Journal of Molecular Sciences, 2022, Vol 23, Issue 11, p5864
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms23115864