Percutaneous splenic nerve stimulation attenuates psoriasis-like dermatitis in rats in an α7nAChR-dependent manner with suppression of cutaneous CGRP/IL-23 signalling

Background Psoriasis is a chronic immune-mediated inflammatory skin disease in which neuro-immune crosstalk is increasingly recognised as a pathogenic driver, and current pharmacological options remain constrained by efficacy, safety, cost and long-term adherence. Objective To determine whether percutaneous splenic nerve stimulation (PSNS) attenuates imiquimod (IMQ)-induced psoriasis-like dermatitis in rats, and whether the effect depends on α7 nicotinic acetylcholine receptor (α7nAChR)-mediated suppression of the calcitonin gene-related peptide (CGRP)/interleukin-23 (IL-23) axis. Methods Psoriasis-like dermatitis was induced in Sprague-Dawley rats by daily topical IMQ. Seven groups (n = 6 each) received, concurrently with IMQ, daily PSNS at 0, 1, 10 or 20 mA, or PSNS at 10 or 20 mA preceded by intraperitoneal α-bungarotoxin (α-BGT, 1 µg/kg); a sham group received petrolatum only. After 10 days, dorsal lesions were scored with the Psoriasis Area and Severity Index (PASI) and skin, liver and kidney were examined histologically (Baker score); serum alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen and creatinine were measured; CGRP, α7nAChR, tumour necrosis factor-α (TNF-α) and IL-23 were quantified by western blotting and ELISA. Results IMQ produced diffuse erythema, thick scaling and acanthosis, with PASI and Baker scores well above those of sham rats (P < 0.05). Stimulation at 1 mA had no measurable effect on any endpoint. At 10 and 20 mA, PASI and Baker scores fell close to sham values, splenic noradrenaline and acetylcholine rose, and splenic TNF-α together with cutaneous CGRP, IL-23 and TNF-α decreased (P < 0.05); 20mA conferred no additional benefit over 10 mA. α7nAChR protein was up-regulated in skin and spleen at 10 and 20 mA. Pre-treatment with α-BGT abolished the protection and restored cutaneous CGRP, IL-23 and TNF-α, without preventing α7nAChR up-regulation. No hepatic or renal histopathological change, and no serum biochemical abnormality were detected. Conclusions PSNS attenuates IMQ-induced psoriasis-like dermatitis once a 10 mA intensity threshold is reached, and the protection requires functional α7nAChR. Transcutaneous access to the splenic neuro-immune circuit may offer a non-pharmacological adjunct in psoriasis, pending confirmation in therapeutic-start and chronic models.