Shentong Zhuyu decoction ameliorates postherpetic neuralgia in rats by regulating cAMP/PKA/p-CREB signaling

Abstract

Postherpetic neuralgia (PHN) is a debilitating chronic pain condition characterized by allodynia and hyperalgesia. Shengtong Zhuyu decoction (STZYD), a traditional Chinese medicine formula used clinically for pain associated with arthralgia syndromes and blood stasis obstructing the collaterals, was investigated for its potential role and mechanism in alleviating PHN. PHN was induced in male Sprague-Dawley rats via intraperitoneal injection of resiniferatoxin (RTX). STZYD was administered intragastrically to RTX-treated rats for 14 consecutive days. Its chemical components were identified using UHPLC-MS/MS. Analgesic efficacy was assessed by measuring mechanical paw withdrawal threshold and thermal paw withdrawal latency. The expression level of TRPV1 (a nociceptor and heat sensor) was analyzed using western blotting and immunofluorescence staining. ELISA was used to measure the levels of proinflammatory cytokines (IL-6, IL-1β, and TNF-α). Apoptosis was detected via TUNEL staining and western blotting. Underlying molecular mechanisms were evaluated using western blotting and immunohistochemistry. STZYD alleviated increased mechanical withdrawal threshold and thermal withdrawal latency and reducing TRPV1 levels in RTX-induced PHN rats. STZYD downregulated the levels of proinflammatory cytokines and pro-apoptotic proteins, reduced the number of TUNEL-positive cells, and upregulated the levels of anti-apoptotic proteins in RTX-induced PHN rats. Moreover, STZYD downregulated cAMP, PKA, and BNDF protein levels and inhibited CREB phosphorylation in RTX-induced PHN rats. Pharmacological activation of PKA by 8-Br-cAMP counteracted the protective effect of SDZYD in PHN rats. STZYD ameliorates RTX-induced mechanical allodynia and thermal hyperalgesia in rats by suppressing inflammation and DRG cell apoptosis through the inhibition of the cAMP/PKA/p-CREB signaling axis.