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Mol Pain. 2016 Jun 15;12. pii: 1744806916656846. doi: 10.1177/1744806916656846. Print 2016.

EXPRESS: NGF-trkA signaling modulates the analgesic effects of prostatic acid phosphatase in resiniferatoxin-induced neuropathy.

Author information

1
Kaohsiung Medical University Chung Ho Memorial Hospital.
2
Kaohsiung Medical University.
3
Kaohsiung Medical University Hospital.
4
Kaohsiung Medical University Chung Ho Memorial HospitalKaohsiung Medical UniversityKaohsiung Medical UniversityKaohsiung Medical University Hospital ylhsieh@kmu.edu.tw.

Abstract

BACKGROUND:

Neuropathic pain in small-fiber neuropathy results from injury to and sensitization of nociceptors. Functional prostatic acid phosphatase (PAP) acts as an analgesic effector. However, the mechanism responsible for the modulation of PAP neuropathology, which leads to loss of the analgesic effect after small-fiber neuropathy, remains unclear.

RESULTS:

We used a resiniferatoxin (RTX)-induced small-fiber neuropathy model to examine whether functional PAP(þ) neurons are essential to maintain the analgesic effect. PAP(þ) neurons were categorized into small to medium neurons (25th-75th percentile: 17.1-23.7 mm); these neurons were slightly reduced by RTX (p¼0.0003). By contrast, RTX-induced activating transcription factor 3 (ATF3), an injury marker, in PAP(þ) neurons (29.0%5.6% vs. 0.2%0.2%, p¼0.0043), indicating PAP neuropathology. Moreover, the high-affinity nerve growth factor (NGF) receptor (trkA) colocalized with PAP and showed similar profiles after RTX-induced neuropathy, and the PAP/trkA ratios correlated with the degree of mechanical allodynia (r¼0.62, p¼0.0062). The NGF inducer 4-methylcatechol (4MC) normalized the analgesic effects of PAP; specifically, it reversed the PAP and trkA profiles and relieved mechanical allodynia. Administering 2.5S NGF showed similar results to those of administering 4MC. This finding suggests that the analgesic effect of functional PAP is mediated by NGF-trkA signaling, which was confirmed by NGF neutralization.

CONCLUSIONS:

This study revealed that functional PAP(þ) neurons are essential for the analgesic effect, which is mediated by NGF-trkA signaling.

PMID:
27306411
PMCID:
PMC4956004
DOI:
10.1177/1744806916656846
[Indexed for MEDLINE]
Free PMC Article

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