RGD Reference Report - The effect of Anti-NGF receptor (p75 Neurotrophin Receptor) antibodies on nociceptive behavior and activation of spinal microglia in the rat brachial plexus avulsion model.

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The effect of Anti-NGF receptor (p75 Neurotrophin Receptor) antibodies on nociceptive behavior and activation of spinal microglia in the rat brachial plexus avulsion model.
Authors:	Matsuura, Y Iwakura, N Ohtori, S Suzuki, T Kuniyoshi, K Murakami, K Hiwatari, R Hashimoto, K Okamoto, S Shibayama, M Kobayashi, T Ogawa, Y Sukegawa, K Takahashi, K
Citation:	Matsuura Y, etal., Spine (Phila Pa 1976). 2013 Mar 15;38(6):E332-8. doi: 10.1097/BRS.0b013e318285ee20.
RGD ID:	10413898
Pubmed:	PMID:23324933 (View Abstract at PubMed)
DOI:	DOI:10.1097/BRS.0b013e318285ee20 (Journal Full-text)
STUDY DESIGN: We measured the response of the behavior and spinal glial activation to anti-nerve growth factor receptor (p75 neurotrophin receptor [p75NTR]) antibodies in the rat brachial plexus avulsion (BPA) model. OBJECTIVE: The aim of this study was to investigate the effect of anti-p75NTR antibodies on nociceptive behavior and activation of spinal microglia in the rat BPA model. SUMMARY OF BACKGROUND DATA: Tanezumab (anti-nerve growth factor antibody) treatment is associated with pain reduction and improvement in function, but with several complications. METHODS: Thirty male Wistar rats were used. In the BPA group, the C8-T1 roots were avulsed from the spinal cord with forceps at the lower trunk level and 10 muL of saline was applied locally (n = 10). In the anti-p75NTR group, the C8-T1 roots were avulsed and 10 muL of anti-p75NTR antibody was applied locally (n = 10). In a sham-operated group, the lower trunk was simply exposed (n = 10). Mechanical hyperalgesia and pain-induced walking patterns were measured using von Frey filaments (Stoelting, Wood Dale, IL) and the CatWalk gait analysis (Noldus Information Technology, the Netherlands) system every third day for 3 weeks. Activation of astrocytes and microglia was immunohistochemically examined in the spinal cord using anti-glial fibrillary acidic protein (GFAP) and anti-Iba1 antibodies both 7 and 21 days after surgery. RESULTS: Animals in the BPA group displayed significant mechanical hyperalgesia that continued through day 21 compared with animals in the sham-operated group, and mechanical hyperalgesia in the anti-p75NTR group was significantly improved 6 days after the operation. Regarding pain-induced gait analysis via CatWalk, animals in the BPA group displayed a significantly greater pain-like gait pattern than the p75 group for up to 3 weeks. Levels of GFAP-immunoreactive astrocytes and Iba1-immunoreactive microglia in the anti-p75NTR group were significantly reduced compared with the BPA group. CONCLUSION: Our results suggest that p75NTR contributes to neuropathic pain associated with BPA, and that inhibition of p75NTR reduces neuropathic pain. LEVEL OF EVIDENCE: N/A.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
Hyperalgesia	treatment	ISO	Ngfr (Rattus norvegicus)	10413898; 10413898	associated with Brachial Plexus Neuropathies	RGD
Hyperalgesia	treatment	IMP		10413898	associated with Brachial Plexus Neuropathies	RGD

Objects Annotated

Genes (Rattus norvegicus)

Ngfr (nerve growth factor receptor)

Genes (Mus musculus)

Ngfr (nerve growth factor receptor (TNFR superfamily, member 16))

Genes (Homo sapiens)

NGFR (nerve growth factor receptor)

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The effect of Anti-NGF receptor (p75 Neurotrophin Receptor) antibodies on nociceptive behavior and activation of spinal microglia in the rat brachial plexus avulsion model.