Acid mediates a prolonged antinociception via substance P signaling in acid-induced chronic widespread pain
1 Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan
2 Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
3 Taiwan Mouse Clinic-National Comprehensive Mouse Phenotyping and Drug Testing Center, Academia Sinica, Taipei 115, Taiwan
4 128 Academia Road, Section 2, Taipei 115, Taiwan
Molecular Pain 2014, 10:30 doi:10.1186/1744-8069-10-30Published: 21 May 2014
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.
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.
Acid could mediate a prolonged antinociceptive signaling via the release of substance P from muscle afferent neurons in a non-ASIC3, non-TRPV1 manner.