Acid Mediates a Prolonged Antinociception via Substance P Signaling in Acid-Induced Chronic Widespread Pain. (21st May 2014)

• Record Type: Journal Article
• Authors: Chen, Wei-Nan; Chen, Chih-Cheng
• Is Part Of: Molecular pain. Volume 10(2014)
• Publication Date: 2014-05-21
• Subjects: Antinociception -- ASIC3 -- TRPV1 -- Muscle pain -- Nociceptor; Pain -- Molecular aspects -- Periodicals; Pain -- Pathophysiology -- Periodicals; Pain -- Physiological aspects -- Periodicals; 616.0472
• DOI: 10.1186/1744-8069-10-30
• Languages: English
• ISSNs: 1744-8069

Abstract

Background: Substance P is an important neuropeptide released from nociceptors to mediate pain signals. We recently revealed antinociceptive signaling by substance P in acid-sensing ion channel 3 (ASIC3)-expressing muscle nociceptors in a mouse model of acid-induced chronic widespread pain. However, methods to specifically trigger the substance P antinociception were still lacking. Results: Here we show that acid could induce antinociceptive signaling via substance P release in muscle. We prevented the intramuscular acid-induced hyperalgesia by pharmacological inhibition of ASIC3 and transient receptor potential V1 (TRPV1). The antinociceptive effect of non-ASIC3, non-TRPV1 acid signaling lasted for 2 days. The non-ASIC3, non-TRPV1 acid antinociception was largely abolished in mice lacking substance P. Moreover, pretreatment with substance P in muscle mimicked the acid antinociceptive effect and prevented the hyperalgesia induced by next-day acid injection. Conclusions: Acid could mediate a prolonged antinociceptive signaling via the release of substance P from muscle afferent neurons in a non-ASIC3, non-TRPV1 manner.