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Role of low-affinity nerve growth factor receptor inhibitory antibody in reducing pain behavior and calcitonin gene-related Peptide expression in a rat model of wrist joint inflammatory pain.
J Hand Surg Am. 2010 Feb; 35(2):267-73.JH

Abstract

PURPOSE

Nerve growth factor (NGF), via the high-affinity receptor, tyrosine kinase A, has been widely reported as a mediator of pain caused by inflammation. A clinical trial has suggested that anti-NGF antibody is effective for pain caused by osteoarthritis of the knee. However, adverse events such as headache (8.9%), upper respiratory tract infection (7.3%), and paresthesia (6.8%) were reported. We hypothesized that inhibition of the low-affinity NGF receptor, p75 neurotrophin receptor (p75NTR), is also effective for joint pain and may reduce side effects. This study examined suppression of pain behavior and expression of pain-inducing neuropeptides such as calcitonin gene-related peptide (CGRP) and p75NTR in dorsal root ganglia neurons by a p75NTR inhibitory antibody in a rat model of wrist joint inflammatory pain.

METHODS

We injected complete Freund's adjuvant (CFA) into the wrist joint of rats and used this as a model of inflammatory pain. We applied 10 microL of saline (CFA + saline group; n = 20) or 1, 10, or 50 microL of a p75NTR inhibitory antibody (CFA + p75NTR inhibitory antibody group; n = 40) directly to the inflamed joint in the rats. Mechanical hyperalgesia was measured for 2 weeks using von Frey filaments. We assessed CGRP and p75NTR expression in C8 dorsal root ganglia immunochemically. Adverse events such as loss of weight and/or appetite, constipation, and infection were examined.

RESULTS

p75NTR inhibitory antibody reduced mechanical hyperalgesia caused by CFA (p<.05 vs controls) in the rat model (p<.01 vs saline), without any adverse events. We found that 10 and 50 microL of a p75NTR inhibitory antibody were more effective for pain, without a significant difference between doses. CGRP and p75NTR immunoreactivity was upregulated in the CFA + saline groups compared with a control group (p<.01). However, direct p75NTR inhibitory antibody application decreased CGRP and p75NTR expression after wrist inflammation (p<.01).

CONCLUSIONS

p75NTR inhibition may be a therapeutic target for inflamed joint pain treatment with reduced adverse events.

Authors+Show Affiliations

Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan. niwakura@qf7.so-net.ne.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

20060234

Citation

Iwakura, Nahoko, et al. "Role of Low-affinity Nerve Growth Factor Receptor Inhibitory Antibody in Reducing Pain Behavior and Calcitonin Gene-related Peptide Expression in a Rat Model of Wrist Joint Inflammatory Pain." The Journal of Hand Surgery, vol. 35, no. 2, 2010, pp. 267-73.
Iwakura N, Ohtori S, Orita S, et al. Role of low-affinity nerve growth factor receptor inhibitory antibody in reducing pain behavior and calcitonin gene-related Peptide expression in a rat model of wrist joint inflammatory pain. J Hand Surg Am. 2010;35(2):267-73.
Iwakura, N., Ohtori, S., Orita, S., Yamashita, M., Takahashi, K., & Kuniyoshi, K. (2010). Role of low-affinity nerve growth factor receptor inhibitory antibody in reducing pain behavior and calcitonin gene-related Peptide expression in a rat model of wrist joint inflammatory pain. The Journal of Hand Surgery, 35(2), 267-73. https://doi.org/10.1016/j.jhsa.2009.10.030
Iwakura N, et al. Role of Low-affinity Nerve Growth Factor Receptor Inhibitory Antibody in Reducing Pain Behavior and Calcitonin Gene-related Peptide Expression in a Rat Model of Wrist Joint Inflammatory Pain. J Hand Surg Am. 2010;35(2):267-73. PubMed PMID: 20060234.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of low-affinity nerve growth factor receptor inhibitory antibody in reducing pain behavior and calcitonin gene-related Peptide expression in a rat model of wrist joint inflammatory pain. AU - Iwakura,Nahoko, AU - Ohtori,Seiji, AU - Orita,Sumihisa, AU - Yamashita,Masaomi, AU - Takahashi,Kazuhisa, AU - Kuniyoshi,Kazuki, Y1 - 2010/01/08/ PY - 2009/08/10/received PY - 2009/10/23/revised PY - 2009/10/26/accepted PY - 2010/1/12/entrez PY - 2010/1/12/pubmed PY - 2010/5/21/medline SP - 267 EP - 73 JF - The Journal of hand surgery JO - J Hand Surg Am VL - 35 IS - 2 N2 - PURPOSE: Nerve growth factor (NGF), via the high-affinity receptor, tyrosine kinase A, has been widely reported as a mediator of pain caused by inflammation. A clinical trial has suggested that anti-NGF antibody is effective for pain caused by osteoarthritis of the knee. However, adverse events such as headache (8.9%), upper respiratory tract infection (7.3%), and paresthesia (6.8%) were reported. We hypothesized that inhibition of the low-affinity NGF receptor, p75 neurotrophin receptor (p75NTR), is also effective for joint pain and may reduce side effects. This study examined suppression of pain behavior and expression of pain-inducing neuropeptides such as calcitonin gene-related peptide (CGRP) and p75NTR in dorsal root ganglia neurons by a p75NTR inhibitory antibody in a rat model of wrist joint inflammatory pain. METHODS: We injected complete Freund's adjuvant (CFA) into the wrist joint of rats and used this as a model of inflammatory pain. We applied 10 microL of saline (CFA + saline group; n = 20) or 1, 10, or 50 microL of a p75NTR inhibitory antibody (CFA + p75NTR inhibitory antibody group; n = 40) directly to the inflamed joint in the rats. Mechanical hyperalgesia was measured for 2 weeks using von Frey filaments. We assessed CGRP and p75NTR expression in C8 dorsal root ganglia immunochemically. Adverse events such as loss of weight and/or appetite, constipation, and infection were examined. RESULTS: p75NTR inhibitory antibody reduced mechanical hyperalgesia caused by CFA (p<.05 vs controls) in the rat model (p<.01 vs saline), without any adverse events. We found that 10 and 50 microL of a p75NTR inhibitory antibody were more effective for pain, without a significant difference between doses. CGRP and p75NTR immunoreactivity was upregulated in the CFA + saline groups compared with a control group (p<.01). However, direct p75NTR inhibitory antibody application decreased CGRP and p75NTR expression after wrist inflammation (p<.01). CONCLUSIONS: p75NTR inhibition may be a therapeutic target for inflamed joint pain treatment with reduced adverse events. SN - 1531-6564 UR - https://www.unboundmedicine.com/medline/citation/20060234/Role_of_low_affinity_nerve_growth_factor_receptor_inhibitory_antibody_in_reducing_pain_behavior_and_calcitonin_gene_related_Peptide_expression_in_a_rat_model_of_wrist_joint_inflammatory_pain_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0363-5023(09)00940-X DB - PRIME DP - Unbound Medicine ER -