Involvement of NIPSNAP1, a neuropeptide nocistatin-interacting protein, in inflammatory pain.

Abstract

BACKGROUND:

Chronic pain associated with inflammation is an important clinical problem, and the underlying mechanisms remain poorly understood. 4-Nitrophenylphosphatase domain and nonneuronal SNAP25-like protein homolog (NIPSNAP) 1, an interacting protein with neuropeptide nocistatin, is implicated in the inhibition of tactile pain allodynia. Although nocistatin inhibits some inflammatory pain responses, whether NIPSNAP1 affects inflammatory pain appears to be unclear. Here, we examined the nociceptive behavioral response of NIPSNAP1-deficient mice and the expression of NIPSNAP1 following peripheral inflammation to determine the contribution of NIPSNAP1 to inflammatory pain.

RESULTS:

Nociceptive behavioral response increased in phase II of the formalin test, particularly during the later stage (26-50 min) in NIPSNAP1-deficient mice, although the response during phase I (0-15 min) was not significantly different between the deficient and wild-type mice. Moreover, phosphorylation of extracellular signal-related kinase was enhanced in the spinal dorsal horn of the deficient mice. The prolonged inflammatory pain induced by carrageenan and complete Freund's adjuvant was exacerbated in NIPSNAP1-deficient mice. NIPSNAP1 mRNA was expressed in small- and medium-sized neurons of the dorsal root ganglion and motor neurons of the spinal cord. In the formalin test, NIPSNAP1 mRNA was slightly increased in dorsal root ganglion but not in the spinal cord. In contrast, NIPSNAP1 mRNA levels in dorsal root ganglion were significantly decreased during 24-48 h after carrageenan injection. Prostaglandin E2, a major mediator of inflammation, stimulated NIPSNAP1 mRNA expression via the cAMP-protein kinase A signaling pathway in isolated dorsal root ganglion cells.

CONCLUSIONS:

These results suggest that changes in NIPSNAP1 expression may contribute to the pathogenesis of inflammatory pain.

• Authors: Kazuya Okamoto, Masaki Ohashi, Kana Ohno, Arisa Takeuchi, Etsuko Matsuoka, Kyohei Fujisato, Toshiaki Minami, Seiji Ito, Emiko Okuda-Ashitaka
• Journal: Molecular pain (Mol Pain) Vol. 12 ( 2016) ISSN: 1744-8069 [Electronic] United States
• PMID: 27030720 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2016.

Chemical References

• Cyclooxygenase Inhibitors
• Intercellular Signaling Peptides and Proteins
• Membrane Proteins
• Neuropeptides
• Nipsnap1 protein, mouse
• Opioid Peptides
• Proteins
• RNA, Messenger
• nocistatin
• Formaldehyde
• Dinoprostone

Topics

• Animals
• Cyclooxygenase Inhibitors (pharmacology)
• Dinoprostone (pharmacology)
• Formaldehyde
• Ganglia, Spinal (drug effects, metabolism)
• Inflammation (complications, genetics, metabolism)
• Intercellular Signaling Peptides and Proteins
• Membrane Proteins
• Mice
• Neuropeptides (metabolism)
• Opioid Peptides (metabolism)
• Pain (complications, metabolism)
• Proteins (genetics, metabolism)
• RNA, Messenger (genetics, metabolism)