Acupoint Injection of Dextrose Attenuates Chronic Inflammatory Pain In Mice Through Modulation of Transient Receptor Potential V1 Channel Expression

Abstract

Background: Neuroinflammatory processes initiated by injury, infection, and other insults induce long-term alterations in the signaling characteristics of nociceptive neurons and associated non-neuronal cells, resulting in chronic inflammatory pain (CIP). Prolotherapy, also termed acupoint injection (AI) therapy, utilizes anatomically based meridians derived from Chinese Medicinal Theory to attenuate chronic pain. In fact, AI has demonstrated superior results compared to traditional acupuncture methods without significant side effects. Methods: In this study, we explored the efficacy and underlying mechanisms of AI on CIP in mice. The mouse hindpaw was injected with complete Freund’s adjuvant (CFA) to induce CIP, followed AI treatment. Results: After two weeks, indices of mechanical and thermal hyperalgesia were significantly reduced by AI treatment. CIP was associated with elevated expression levels of transient receptor potential V1 (TRPV1) channels, various downstream kinases and transcription factors, and nociception-associated voltage-gated sodium channels (Navs) in dorsal root ganglion (DRG), spinal cord, thalamus, and somatosensory cortex, while AI-induced analgesia was associated with reversal of these expression changes. Further, upregulation of TRPV1-associated signaling factors was not observed in Trpv1 knockout mice following CFA injection. In addition, the activated microglial markers Iba-1 and S100B demonstrated similar expression changes and were colocalized with TRPV1. Conclusions: These findings suggest that AI can mitigate chronic pain (and sequel such as comorbid depression) by suppressing TRPV1 overexpression in neuronal or microglial cells.